Medtronic 6972260 Instructions for Use

Instructions for Use 0381422E Rev. D

Prestige LP™ Cervical Disc

Medtronic Sofamor Danek USA, Inc.

1800 Pyramid Place Memphis, TN 38132
Tel. [phone] (In U.S.A.)

901 396 3133 (Outside of U.S.A.)

Fax [phone]

CAUTION: Federal (United States) law restricts this device to sale by or on the order of a

Physician.

HOW SUPPLIED

Prestige LP™ Cervical Disc Implants – Sterile
Surgical Instruments – Non-sterile (unless otherwise noted on the package label)

DEVICE DESCRIPTION

The Prestige LP™ Cervical Disc is a two-piece articulating device that is inserted into the
intervertebral disc space as a pre-assembled unit at one or two contiguous cervical levels using
an anterior approach. The device is manufactured from a titanium ceramic composite (Titanium­6Aluminum-4Vanadium with 10% Titanium Carbide) and consists of two metal plates which
function via a ball and trough mechanism. The superior component of the implant contains the
ball portion of the mechanism, and the inferior component contains the trough portion. These
two features engage to create an interface designed to allow for motion after implantation. Each
component is affixed to the adjacent vertebral body by two rail geometries incorporating anti­migration teeth, which are press fit into two pre-drilled holes in the vertebral bone. The portion
of the flat surface between the rails that contacts the vertebral endplate has a commercially pure
titanium (CP Ti) plasma thermal sprayed coating per ASTM F1580, designed to permit bony on­growth for additional device incorporation. The remaining portion of the flat surface is titanium
ceramic roughened to enhance fixation. Each component also contains two anterior tab features
designed to aid in device insertion and to minimize the risk of implanting the device too far into
the intervertebral space.

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Catalog Number

Size (Height x AP Dimension x ML Dimension)

6972250

5mm x 12mm x 15mm

6972450

5mm x 14mm x 15mm

6972650

5mm x 16mm x 15mm

6972260

6mm x 12mm x 17. 8m m

6972460

6mm x 14mm x 17. 8m m

6972660

6mm x 16mm x 17. 8m m

6972860

6mm x 18mm x 17. 8m m

6972470

7mm x 14mm x 17. 8m m

6972670

7mm x 16mm x 17. 8m m

6972870

7mm x 18mm x 17. 8m m

6972480

8mm x 14mm x 17. 8m m

6972680

8mm x 16mm x 17. 8m m

6972880

8mm x 18mm x 17.8mm

Figure 1a: Prestige LP™ Cervical Disc Figure 1b: Prestige LP™ Cervical

Disc at two contiguous levels

The Prestige LP™ Cervical Disc i s offered in a variety of configurations to accommodate varied
patient anatomy. The available components are shown in Table 1 below.

The Prestige LP™ Cervical Disc is designed to allow a minimum of 10 degrees lateral bending
(from neutral) and a minimum of 10 degrees flexion/extension (from neutral). The design is also
intended to allow unlimited axial rotation (constrained by ligaments and posterior elements) and
translation of 2mm in the sagittal plane.

Table 1: Prestige LP™ Cervical Disc Device Sizes

The Prestige LP™ Cervical Disc is implanted using instruments specific to the device, as well as
manual surgical instruments. Instruments specifically designed for implanting Prestige LP™
Cervical Disc consist of trials, trial cutter guides, rail punches, and implant inserters. General
purpose instruments include instruments for cervical distraction and discectomy preparation.

No warranties, expressed or implied, are made. Implied warranties of merchantability and fitness
for a particular purpose or use are specifically excluded.

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INDICATIONS FOR USE

The Prestige LP™ Cervical Disc is indicated in skeletally mature patients for reconstruction of
the disc from C3-C7 following discectomy at one level or two contiguous levels for intractable
radiculopathy (arm pain and/or a neurological deficit) with or without neck pain, or myelopathy
due to abnormality localized to the level of the disc space and at least one of the following
conditions confirmed by imaging (CT, MRI, X-rays): herniated nucleus pulposus, spondylosis
(defined by the presence of osteophytes), and/or visible loss of disc height as compared to
adjacent levels. The Prestige LP™ Cervical Disc is implanted using an anterior approach.
Patients should have failed at least 6 weeks of non-operative treatment or have had the presence
of progressive symptoms or signs of nerve root/spinal cord compression in the face of continued
non-operative management prior to implantation of the Prestige LP™ Cervical Disc.

CONTRAINDICATIONS

The Prestige LP™ Cervical Disc should not be implanted in patients with the following
conditions:

• Active systemic infection or localized infection at the surgical site;

• Osteoporosis or osteopenia defined as a DEXA bone mineral density T-score ≤ -1.0;

• Allergy or sensitivity to titanium, aluminum or vanadium;

• Marked cervical instability on neutral resting lateral or flexion/extension radiographs;

translation >3.5mm and/or >11° rotational difference from that of either level adjacent to
the treated levels;

• Severe spondylosis at the level to be treated, characterized by bridging osteophytes, loss

of disc height >50%, an absence of motion (<2°) as this may lead to a limited range of
motion and may encourage bone formation (e.g. heterotopic ossification, fusion);

• Severe facet joint arthropathy;

• Significant cervical anatomical deformity or clinically compromised vertebral bodies at

the affected level(s) due to current or past trauma (e.g., by radiographic appearance of
fracture callus, malunion or nonunion) or disease (e.g., ankylosing spondylitis,
rheumatoid arthritis); or

• Significant kyphotic deformity or significant reversal of lordosis.

WARNINGS

The Prestige LP™ Cervical Disc should only be used by surgeons who are experienced with
anterior cervical spinal procedures and have undergone adequate hands-on training in the use of
this specific device. Only surgeons who are familiar with the implant components, instruments,
procedure, clinical applications, biomechanics, adverse events, and risks associated with the
Prestige LP™ Cervical Disc should use this device. Medtronic will offer hands-on training to
physicians prior to their first use of the device. A lack of adequate experience and/or training
may lead to a higher incidence of adverse events, including neurological complications.

Correct sizing and placement of the device is essential to optimal performance. Information
regarding proper implant size selection, implant site preparation, and the use of instrumentation
before, during and after Prestige LP™ surgery is provided in the Prestige LP™ Cervical Disc
Surgical Technique manual. Users are advised to read and understand the surgical technique
manual and instructions for use prior to surgery.

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Due to the proximity of vascular and neurological structures to the implantation site, there are
risks of serious or fatal hemorrhage and risks of neurological damage with the use of this device.
Serious or fatal hemorrhage may occur if the great vessels are eroded or punctured during
implantation or are subsequently damaged due to breakage of implants, migration of implants, or
if pulsatile erosion of the vessels occurs because of close apposition of the implants. Care must
be taken to identify and protect these structures.

Heterotopic Ossification (HO) is a potential complication associated with artificial cervical discs
and could lead to reduced cervical motion.

Devices with metal-on-metal articulating surfaces (such as the Prestige LP™ Cervical Disc) may
release wear debris, metallic particles or metal ions locally near the device and/or systemically.
The short and long term effects of the wear debris, metallic particles and metal ions on the body
are not known, but certain groups of patients may be at a higher risk including patients who are
pregnant, patients who are planning to get pregnant, and patients who have renal disease.

PRECAUTIONS

The safety and effectiveness of this device has not been established in patients with the following
conditions:

• Axial neck pain as the solitary symptom;

• Skeletally immature patients, pediatric or adolescent children (<21 years old), or those

over the age of 78;

• Prior cervical spine surgery, including prior surgery at the index level or adjacent levels;

• More than two cervical discs or two non-adjacent cervical discs that require surgical

treatment;

• Facet joint pathology of involved vertebral bodies;

• Spinal metastases;

• An endocrine or metabolic disease that affects bones such as Paget’s disease,

osteomalacia, renal osteodystrophy, Ehlers-Danlos Syndrome, or osteogenesis
imperfecta;

• Chronic or acute renal failure or history of renal disease;

• Taking medications known to potentially interfere with bone/soft tissue healing (e.g.,

steroids);

• Diabetes mellitus requiring daily insulin management;

• Serious mental illness;

• Being treated for alcohol and/or drug abuse; and

• Pregnant.

Pre-operative

Patient selection is extremely important. In selecting patients for a total disc replacement, the
following factors may negatively affect the success of the procedure: the patient’s occupation or
activity level; prior injury or ongoing illness (e.g., Alzheimer’s disease, emphysema); alcoholism
or drug abuse; and certain degenerative diseases (e.g., degenerative scoliosis, ankylosing
spondylitis) that may be so advanced at the time of implantation that the expected useful life of
the device is substantially diminished.

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In order to minimize the risk of periprosthetic vertebral fractures, surgeons must consider all co­morbidities, past and present medications, previous treatments, etc. Surgeons should screen
patients to determine if a DEXA bone mineral density measurement is necessary. If DEXA is
performed, the patient should not receive the Prestige LP™ Cervical Disc (per the
contraindications listed above) if the DEXA bone mineral density T-score is ≤ -1.0, as the patient
may be osteoporotic or osteopenic.

The patient should be informed of the potential adverse effects (risk/complications) contained in
this insert (see POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH).

Preoperative planning may be used to estimate the required implant size and to assure that the
appropriate range of sizes is available for surgery. Specific preoperative planning is necessary
when performing a two-level procedure. The procedure should not take place if the appropriate
range of sizes will not be available.

Inspect all instruments prior to surgery and replace any worn or damaged items. Instruments
which have been used excessively may be more likely to break.

Intra-operative

Correct selection of the appropriate implant size is extremely important to ensure the placement
and function of the disc. When performing a two-level procedure, to ensure sufficient access to
the two affected disc spaces, make the skin incision centered at the middle vertebral body. A
standard incision for the exposure of two levels is required. See the surgical technique manual
for step-by-step instructions on the surgical technique, including determining the correct implant
size.

Use aseptic technique when removing the Prestige LP™ Cervical Disc components from the
innermost packaging. Carefully inspect each component and its packaging for any signs of
damage, including damage to the sterile barrier. Do not use Prestige LP™ Cervical Disc
components if the packaging is damaged or the implant shows signs of damage.

Use care when handling a Prestige LP™ Cervical Disc component to ensure it does not come in
contact with objects that could damage the implant. Exercise care to ensure implantation
instruments do not contact the highly polished articulating surfaces of the endplates. Damaged
implants are no longer functionally reliable. Visual inspection of the Prestige LP™ Cervical Disc
assembly is recommended prior to implantation. If any part of the assembly appears damaged, do
not use the device.

When preparing the disc space, remove anterior or posterior osteophytes as needed, taking care
to perform a complete discectomy while minimizing bone removal, as excessive bone removal
may weaken the vertebral endplates or vertebral body.

Correct positioning of the rail punch is critical prior to performing the rail preparation step. Care
should be taken to correctly position the rail punch during this step.

Ensure proper alignment and placement of the Prestige LP™ Cervical Disc as misalignment may
cause excessive wear and/or early failure of the device.

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In a two-level procedure, when placing the first implant, pay special attention to implant height
selection. The goal is to balance the discs to achieve normal sagittal balance and disc space
height. Before placing the first implant, it is important to verify normal sagittal balance and disc
space height by using the Implant Trials. Achieve this by preoperative templating, careful
trialing under lateral fluoroscopy, and comparing the facet and intradiscal heights in healthy
adjacent levels. Implant Trials should fit snugly without distracting the disc spaces.

The Prestige LP™ Cervical Disc components should not be used with components or
instruments of spinal systems from other manufacturers. See the surgical technique manual for
step-by-step instructions.

The Prestige LP™ Cervical Disc implants are designed for single patient use only. Do not re-use,
re-process, or re-sterilize the implants. Even if the device appears undamaged, re-use, re­processing, or re-sterilization may compromise the structural integrity of the implant and the
intended function of the device which could result in patient injury.

Post-operative

Patients in the clinical study of the Prestige LP™ Cervical Disc were instructed to use non­steroidal anti-inflammatory drugs (NSAIDs) for two weeks postoperatively. It has been reported
in the literature that short-term postoperative use of NSAIDs may reduce the instance of
heterotopic ossification (HO). To reduce the instance of HO, it is recommended that the Prestige
LP™ device be implanted in subjects able to tolerate the use of NSAIDs for two weeks post­operatively.

Patients should be instructed in postoperative care procedures and should be advised of the
importance of adhering to these procedures for successful treatment with the device. Patients
should be advised to avoid any activities that require repeated bending or twisting, heavy lifting,
and challenging activities such as athletic activities. Gradual increase in physical activity will
depend on individual patient progress.

MRI Safety Information

In non-clinical testing the Prestige LP™ Cervical Disc implanted at either a single level or two
contiguous levels was determined to be MR-conditional. A patient with this device can be
scanned safely, immediately after placement, under the following conditions:

• Static magnetic field of 1.5-Tesla and 3.0-Tesla.

• Maximum spatial gradient magnetic field of 3000-Gauss/cm or less.

• Maximum whole body average specific absorption rate (SAR) of 4.0 -W/kg or less under

Normal Operating Mode or first level controlled operating mode.

• Body Coil only.

Under the scan conditions defined above, the Prestige LP™ Cervical Disc is expected to produce
a maximum temperature rise of less than 4.0°C after 15 minutes of continuous scanning.

In non-clinical testing, the image artifact caused by the device extends approximately 20 mm
from the Prestige LP™ Cervical Disc when imaged with a gradient echo pulse sequence in a 3.0

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Tesla MRI system.
If the Prestige LP™ Cervical Disc is used in connection with any device which is not

MR Conditional, please be advised that this combination has not been tested in the MR
environment and, therefore, higher heating and possible injury to the patient may occur.

The presence of other implants or the health state of the patient may require a modification of the
MR conditions.

POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the potential adverse effects (e.g., complications) associated with the use of the
Prestige LP™ Cervical Disc identified from the Prestige LP™ Cervical Disc clinical study
results, approved device labeling for other cervical total disc replacement devices, and published
scientific literature including: (1) those associated with any surgical procedure; (2) those
associated with anterior cervical spine surgery; and (3) those associated with a cervical artificial
disc device, including the Prestige LP™ Cervical Disc. In addition to the risks listed below, there
is also the risk that surgery may not be effective in relieving symptoms, or may cause worsening
of symptoms. Additional surgery may be required to correct some of the adverse effects.

1. Risks associated with any surgical procedure include:

• Anesthesia complications including an allergic reaction or anaphylaxis;

• Infection (wound, local, and/or systemic) or abscess;

• Wound dehiscence or necrosis;

• Edema;

• Soft tissue damage or fluid collections, including hematoma or seroma;

• Pain/discomfort at the surgical incision and/or skin or muscle sensitivity over the incision

which may result in skin breakdown, pain, and/or irritation;

• Heart or vascular complications including bleeding, hemorrhage or vascular damage

resulting in catastrophic or potentially fatal bleeding, ischemia, myocardial infarction,
abnormal blood pressure, venous thromboembolism including deep vein thrombosis and
pulmonary embolism, thrombophlebitis, or stroke;

• Pulmonary complications including atelectasis or pneumonia;

• Impairment of the gastrointestinal system including ileus or bowel obstruction;

• Impairment of the genitourinary system including incontinence, bladder dysfunction, or

reproductive system complications;

• Neurological complications including nerve damage, paralysis, seizures, changes to

mental status, or reflex sympathetic dystrophy;

• Complications of pregnancy including miscarriage or congenital defects;

• Inability to resume activities of daily living; and

• Death.

2. Risks associated with anterior cervical spine surgery include:

• Injury to surrounding organs and structures including the spinal cord, nerve roots, other

neurologic structures adjacent to the spinal column, vocal cords, adjacent vertebrae,
lymphatic vessels, blood vessels, soft tissue, dura, the trachea, the esophagus, the larynx,
or the pharynx;

• Dysphagia, dysphonia, hoarseness, vocal cord paralysis, laryngeal palsy; or sore throat;

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• Tracheal, esophageal, or pharyngeal perforation, fistula, recurrent aspiration, or airway

obstruction;

• Neurological complications, including damage to nerve roots, the spinal cord, or other

nerves possibly resulting in muscle weakness or paralysis, changes in sensation
(including numbness, dysesthesias, or paresthesias), bowel/bladder dysfunction, or pain;

• Neck pain, arm pain, or headache;

• Dural tear or leak or cerebrospinal fistula;

• Discitis, arachnoiditis, or other type of inflammation;

• Loss of disc height; loss of anatomic sagittal plane curvature or vertebral listhesis, spinal

stenosis, or spondylolysis; and

• Scarring, herniation or degeneration of adjacent discs.

3. Risks associated with a cervical artificial disc device, including the Prestige LP™ Cervical

Disc, include:

• Risks directly related to the device including malposition, migration/displacement,

subsidence/loss of disc height, device breakage, device disassembly, or early or late
loosening of the device. Any of these issues may cause pain or injury to surrounding
organs and structures including the spinal cord, nerve roots, or other neurologic structures
adjacent to the spinal column (which could cause pain, paralysis, or numbness) or blood
vessel damage or erosion (which could cause catastrophic or fatal bleeding);

• Deterioration in neurologic status including muscle weakness or paralysis, changes in

sensation (including numbness, dysesthesias, or paresthesias), decreased reflexes, or loss
of bowel and/or bladder control;

• Development of new radiculopathy, myelopathy, or pain;

• Failure of the device to improve symptoms or function;

• Problems during placement of the device including trouble sizing the device, anatomical

or technical difficulties implanting the device, or issues with the device instruments (e.g.,
bending or breakage) including the possibility that a fragment of a broken instrument
may remain in the patient after implantation;

• Adverse reaction or allergy to the device materials (titanium, aluminum or vanadium),

device wear debris or metal ions which may lead to a systemic reaction or a local adverse
tissue reaction or chronic inflammation which may lead to implant loosening or failure of
the device, osteolysis, bone resorption, tumor formation, autoimmune disease, metallosis,
scarring, or other symptoms;

• Change in the alignment of the spine or loss of proper anatomic curvature, correction,

height or reduction of the spine including spondylolisthesis, change in lordosis, or
instability of the spine;

• Degeneration of other parts of the spine including the facet joints or adjacent discs;

• Fracture of the surrounding vertebrae;

• Unintended bone formation (i.e., heterotopic ossification) that may result in bridging

trabecular bone and may reduce spinal motion or result in unintended fusion at either the
treated level or adjacent levels;

• Device failure which may require a subsequent surgical intervention (including removal

of the Prestige LP™ Cervical Disc, revision, re-operation, or supplemental fixation); and

• Interference with radiographic imaging because of the presence of the implant.

NOTE: Some of the adverse effects listed above were observed in the Prestige LP™ Cervical

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Disc clinical studies. For detailed information on the specific adverse events that occurred in the
clinical studies of the Prestige LP™ Cervical Disc, please see Tables 8-10e and 12 for the
single-level study and Tables 31-33 and 35 for the two-level study.

PHYSICIAN NOTE: Although the physician is the learned intermediary between the company
and the patient, the important medical information given in this document should be conveyed to
the patient.

CLINICAL STUDIES

Two clinical studies were conducted to support the safety and effectiveness of the Prestige LP™
Cervical Disc for reconstruction of the disc from C3-C7 following discectomy at one level
(G040086) or two contiguous levels (G050202) for the indications outlined above. The clinical
studies are summarized separately below.

SUMMARY OF THE SINGLE-LEVEL IDE AND POST-APPROVAL STUDY (PAS)
METHOD

The clinical investigation of the Prestige LP™ Cervical Disc was conducted under an approved
IDE #G040086. The study was a prospective, multi-center, non-randomized, unmasked, non­inferiority clinical trial conducted in the United States to compare the safety and effectiveness of
the Prestige LP™ Cervical Disc to the standard of care (a legally marketed alternative with
similar indications for use) anterior cervical discectomy and fusion (ACDF) using structural
allograft and plate stabilization. The control group consisted of a non-randomized historical
control group that received treatment with ACDF for reconstruction of the disc from C3-C7
following single-level discectomy for intractable radiculopathy and/or myelopathy in the
previous IDE randomized trial of the Prestige™ Cervical Disc (#G010188).

The study consisted of 280 patients treated with the investigational device at 20 investigational
centers in the clinical trial, and 265 patients received the control treatment under a previous IDE
study. Fifty-four subjects were enrolled at the same investigational sites, including: 30 patients
enrolled into a Metal Ion Cohort (MI) for which metal ion analysis was conducted based on
blood draws at each follow-up time point; and, 24 Continued Access (CA) patients. A Post­Approval Study required as a condition of PMA approval was also conducted to follow the
original IDE subject cohort through 120 months postoperatively.

Study Objectives
IDE Study

The primary objective of the IDE study was to demonstrate that the overall success rate for the
investigational Prestige LP™ Cervical Disc treatment is statistically non-inferior to the overall
success rate of the control treatment at 24 months following surgery as determined by a
prespecified non-inferiority margin of 0.10. If statistical non-inferiority was established, the
investigational treatment is considered to be safe and effective, and the study was considered a
success.

Secondary objectives were to compare the success rates of individual effectiveness endpoints and
neurological status at 24 months following surgery. The secondary objectives included
demonstrating that the investigational group’s overall success rate was statistically superior to
the control group’s overall success rate at 24 months if the primary objective was met. Secondary

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objectives also included demonstrating the non-inferiority of the success rates of individual
effectiveness endpoints and neurological status at 24 months following surgery in the
investigational group as compared to that in the control group. If the non-inferiority of the
investigational group was established for a particular endpoint, then the superiority would be
tested for that endpoint as well. In addition, secondary objectives included comparing the rate of
adverse events and secondary surgeries between the two groups, and comparing the surgery and
hospital information between the two groups.

Post-Approval Study

The primary objective of the post-approval study (PAS) study was to demonstrate that the overall
success rate for the investigational group is statistically non-inferior to the success rate of the
control treatment at 84 months (7 years) following surgery. If statistical non-inferiority was
established, the investigational treatment is considered to be safe and effective and the study was
considered a success.

Secondary objectives were to compare the success rates of individual effectiveness endpoints and
neurological status at 24 months following surgery. The secondary objectives included
demonstrating that the investigational group’s overall success rate was statistically superiority to
the control group’s overall success rate at 84 months if the primary objective was met. Secondary
objectives also included demonstrating the non-inferiority of the success rates of individual
effectiveness endpoints and neurological status at 84 months following surgery in the
investigational group as compared to that in the control group. If the non-inferiority of the
investigational group was established for a particular endpoint, then the superiority would be
tested as well for that endpoint as well. In addition, secondary objectives included comparing the
rate of adverse event and secondary surgery between the two groups, and comparing the surgery
and hospital information between the two groups.

Study Desig ns
IDE Study

The IDE study was a multi-center, prospective, randomized, controlled clinical trial comparing
the investigational Prestige LP™ Cervical Disc treatment to the control treatment. Data were
collected at pre-operative, discharge, 6 weeks, 3 months, 6 months, 12 months (1 year) and at 24
months (2 years).

PAS Study

The post-approval study was a prospective study to continue follow-up on the subjects who
participated in the IDE study. Data were collected at 36 months (3 years), 60 months (5 years),
84 months (7 years) and 120 months (10 years-for the investigational group only) postoperative
to determine the long-term safety and effectiveness of the device.

Clinical Inc lus ion and E xclu sio n Criteria

To qualify for enrollment in the study, subjects met all of the following inclusion criteria and
none of the following exclusion criteria.

Clinical Inclusion Criteria

Enrollment in the Prestige LP™ study was limited to patients who met the following inclusion
criteria:

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• Cervical degenerative disc disease defined as: intractable radiculopathy and/or

myelopathy with at least one of the following items producing symptomatic nerve root
and/or spinal cord compression documented by patient history [e.g., pain, functional
deficit, and/or neurologic deficit and radiographic studies (e.g., computed tomography
(CT), magnetic resonance imaging (MRI), x-rays, etc.)]

o Herniated disc;
o Osteophyte formation

• One level requiring surgical treatment;

• C3-C4 disc to C6-C7 disc level of involvement;

• Unresponsive to non-operative treatment for approximately six weeks or has the presence

of progressive symptoms or signs of nerve root/spinal cord compression in the face of
continued non-operative management ;

• No previous surgical intervention at involved level or any subsequent, planned/staged

surgical procedure at the involved or adjacent level(s);

• Is at least 18 years of age, inclusive, at the time of the surgery;

• Preoperative Neck Disability Index score of ≥ 30;

• Has a preoperative neck pain score of ≥ 20 on Preoperative Neck and Arm Pain

Questionnaire;

• If a female of child-bearing potential, patient is not pregnant at the time of surgery;

• Is willing to comply with the study plan and sign the Patient Informed Consent Form.

Clinical Exclusion Criteria

Patients were not permitted to enroll in the Prestige LP™ study if any of the following exclusion
criteria were present:

• Has a cervical spinal condition other than symptomatic cervical disc disease requiring

surgical treatment at the involved level;

• Documented or diagnosed cervical instability defined by dynamic (flexion/extension)

radiographs showing sagittal plane translation > 3.5mm or sagittal plane angulation >
20°;

• More than one cervical level requiring surgical treatment;

• Has a fused level adjacent to the level to be treated;

• Has severe pathology of the facet joints of the involved vertebral bodies;

• Previous surgical intervention at the involved level;

• Has previous diagnosis of osteopenia or osteomalacia;

• Has any of the following that may be associated with a diagnosis of osteoporosis (if

“Yes” to any of the below risk factors, a DEXA Scan will be required to determine
eligibility):

o Postmenopausal non-Black female over 60 years of age and weighs less than 140

pounds

o Postmenopausal female that has sustained a non-traumatic hip, spine, or wrist

fracture

o Male over the age of 70
o Male over the age of 60 that has sustained a non-traumatic hip or spine fracture

If the level of bone mineral density (BMD) is a T score of -3.5 or a T score of -2.5 with
vertebral crush fracture, the patient is excluded from the study

• Has presence of spinal metastases;

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• Has overt or active bacterial infection, either local or systemic;

• Has severe insulin dependent diabetes;

• Has chronic or acute renal failure or prior history of renal disease;

• Has fever (temperature > 101°F oral) at the time of surgery;

• Has a documented allergy or intolerance to stainless steel, titanium, or a titanium alloy;

• Is mentally incompetent (if questionable, obtain psychiatric consult);

• Is a prisoner;

• Is pregnant;

• Is an alcohol and/or drug abuser currently undergoing treatment for alcohol and/or drug

abuse

• Has received drugs which may interfere with bone metabolism within two weeks prior to

the planned date of spinal surgery (e.g., steroids or methotrexate) excluding routing
perioperative anti-inflammatory drugs;

• Has a history of an endocrine or metabolic disorder known to affect osteogenesis (e.g.,

Paget’s Disease, renal osteodystrophy, Ehlers-Danlos Syndrome, or osteogenesis
imperfecta);

• Has a condition that requires postoperative medications that interfere with the stability of

the implant, such as steroids. (This does not include low dose aspirin for prophylactic
anticoagulation), excluding routine perioperative anti-inflammatory drugs;

• Has received treatment with an investigational therapy within 28 days prior to

implantation surgery or such treatment is planned during the 16 weeks following
implantation with the Prestige LP™ device.

Study Population

The studies included 280 non-randomized investigational subjects in the IDE study, 30 subjects
in Metal Ion (MI) cohort, and 24 subjects in Continued Access (CA) cohort. The studies also
included 265 historical control subjects in the IDE study.

Postoperative Care

The recommended post-operative care included avoidance of overhead lifting, heavy lifting,
repetitive bending, and high-impact exercise or athletic activity for 60 days postoperatively.
Avoidance of prolonged (beyond 2 weeks post-op) non-steroidal anti-inflammatory drug
(NSAID) use was specified in the postoperative regimen, although the use of NSAIDs was
recommended for the first two weeks post-operatively. Post-operative bracing requirements were
left to the discretion of the investigators and included the option for use of a soft collar as
needed. The use of electrical/external bone growth stimulators was not recommended during the
24 month follow-up period. However, in a few cases where an electrical/external bone growth
stimulator was utilized due to specific patient presentation, they were considered a supplemental
form of therapy for spinal fusion surgery, and deemed failures included in the “Supplemental
Fixation” Adverse Event category. Patients who smoked were encouraged to discontinue
smoking.

Study Visits and Length of Follow-Up

For the IDE study, patients were evaluated preoperatively (within 6 months of surgery),
intraoperatively, and postoperatively at 6 weeks, 3, 6, 12, 24 months, and annually thereafter
until the last subject enrolled in the study had been seen for their 24-month evaluation. For the

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Procedure

Pre-/Peri-Operative

Postoperative

Surgery/

Discharge

Preoperative Information

Confirm Patient Eligibility

X

Obtain Informed Consent

X

Obtain HIPAA Authorization

X

Case Report Forms

Patient Enrollment

X

Patient Qualification

X

Preoperative Data

X

Prior History Questionnaire

X

Neurological Status

X X X X X X

Preoperative Gait Assess men t an d Foraminal

Compression Test

X

Preoperative Patient Survey

X

Preoperative Neck Disability Index

X

Preoperative Neck and Arm Pain Questionnaire

X

Health Status Questionnaire (SF-36)

X X X X

Surgery Data

X

Hospital Discharge

X

Postoperative Data

X X X X X

Postoperative Patient Survey

X X X X X

Neck Disability Index

X X X X X

Postoperative Neck and Arm Pain Questionnaire

X X X X X

Postoperative Gait Assessment and Foraminal

Compression Test

X X X X X

Adverse Event Form (if any)

X X X X X X

Outstanding (Unresolved) Adverse Event (if any)

X X X X X X

Patient Disposition

X X X X X

Imaging – Radiographs and Scans*

Anterior/Posterior X-ray

X X X X X X X

Lateral X-ray

X X X X X X X

Right/Left Lateral Bend X-rays

X X X X X X

Flexion/Extension X-rays

X X X X X X

CT and/or MRI

X

DEXA Scan **

X

PAS, patients were evaluated at 36, 60, 84 and 120 months. Complications and adverse events
were evaluated over the course of the clinical trial. The length of follow-up for individual
subjects was up to 120 months (10 years). At each evaluation timepoint, the primary and
secondary clinical and radiographic outcome parameters were evaluated as shown in Table 2.
Success was determined from data collected up to 84 months.

Table 2: Schedule of Study Assessments

Pre-OP

Hospital

6 wks ±2

wks

3 mo. ±2

wks

6 mo. ± 1

mo.

12 mo. ±

2mo.

24 mo. ± 2 mo.

& Beyond

* Patients who sign cons ent and are screened eligibl e, but who do not receive the Prestige LP™ device, were not required to ha ve t he
preoperative radiographs obtained and forwarded to Medtronic.
** A DEXA Scan was only required if the patient had a risk factor that may be associated with a diagnosis of osteoporosis.

Data Source

New data collection

IDE and PAS Key Study Endpoints

The safety of the Prestige LP™ Cervical Disc was assessed by comparison to the historical
control group with respect to the nature and frequency of adverse events, secondary surgical
procedures, as well as maintenance or improvement in neurological status.

The effectiveness of the Prestige LP™ Cervical Disc device was assessed using a composite
definition of study success. The primary endpoint used for assessment of effectiveness was
improvement in Neck Disability Index (NDI) pain/disability scores.

Medtronic Page 13 of 103

In addition, several radiograph-assisted assessments were considered in evaluating both safety
and effectiveness including device subsidence, functional spinal unit (FSU) height maintenance,
device migration, and device breakage.

According to the final IDE and PAS protocol, an individual patient in either treatment group was
considered an overall success if the following criteria were met at 24 months for the IDE and 84
months for the PAS:

• An improvement (reduction) of at least 15 points from the baseline Neck Disability Index

score;

• Maintenance or improvement in neurological status;

• Disc height (Functional Spinal Unit Height) success (FSU success)

• No severe adverse event classified as implant-associated, surgical procedure-associated, or

implant/surgical procedure-associated; and

• No additional surgical procedure classified as “Failure”

An alternative analysis of the primary endpoint analysis was also conducted without the addition
of FSU height as a success criterion.

Secondary endpoints, measured in both treatment groups, included Radiographic Success, neck
pain (VAS), arm pain (VAS), quality of life (SF-36 PCS and MCS scores), patient satisfaction,
patient global perceived effort, gait assessment (Nurick’s classification), and foraminal
compression test. Additional measurements recorded were adjacent level stability, return to
work, and doctor’s perception of results. Radiographic Succcess for maintenance of motion is
defined as >4° but <=20° of angular motion based on lateral flexion/extension radiographs and
no radiographic evidence of bridging trabecular bone that forms a continuous bony connection
with the vertebral bodies (bridging bone).

Criteria for the success of the control group was defined in a previous IDE study (G010188).
Briefly, the same success criteria for the primary endpoints exist for the control group as the
investigational group, with the exception that the secondary endpoint for radiographic success
was defined by radiographic evidence of bone spanning the two vertebral bodies, existence of
angular motion stability <=4°, and no radiolucent lines covering more than 50% of the implant
surface.

Total number of Enrolled Study Sites and Subjects, Follow-up Rate

A total of 24 investigators and sub-investigators participated at 15 investigational sites in the
United States. The subject accountability data (includes subjects evaluated and percent follow-up
rate) are summarized in Table 3. Please note that Continued Access Cohort (CA) and the Metal
Ion Cohort (MI) were enrolled separately from the IDE Cohort at the same study sites. Safety
and effectiveness data were collected for the IDE, Safety (IDE+CA+MI), and ACDF Control
Cohorts while the statistical analyses were performed with the IDE Cohort in comparison to the
control group.

Medtronic Page 14 of 103

IDE 12 Months

IDE 24 Months

PAS 84 Months

PAS 120 Months

restige

IDE Cohort ACDF

Control

restige

Safety Cohort

restige

IDE Cohort ACDF

Control

restige

Safety Cohort

restige

PAS

ACDF

Control

restige

Safety Cohort

restige

PAS

ACDF

ontrol

restige

Safety Cohort

Enrolled

280

265

333

280

265

333

280

265

333

280 - 333

Theoretica l F ollow-up

280

265

333

280

265

333

280

265

333

280 - 333

Cumulative D eaths1

0 1 0 0 2 0 3 5 3 4 - 5 Cumulative Wi th drawals

1 6 1 1 8 1 9

13

12

12 - 16

Cumulati ve L ost-to­Follow Up

Expected2

279

244

332

278

235

331

258

196

305

254 - 299

Evaluabl e for Overall

(% of Total Expected)

Evaluabl e for Overall

(% of Total Expected)

Percent Follow-up

98.6%

94.7%

98.8%

97.8%

96.6%

98.2%

82.2%

95.4%

84.6%

90.9%

-

92.3%

Prestige LP™ IDE/PAS

(N=280)

p-value

Control)

Age (years)

44.5 ± 8.8

Range: 23 - 78

43.9 ± 8.8

Range: 22 – 73

43.8 ± 9.0

Range: 23 – 78

Table 3: Subject Accountability

Number of Patients

Success

Success, In Window

LP™

P

0 14 0 1 20 1 10 51 13 10 - 13

274

(98.2%)

271

(98.9%)

223

(91.4%)

206

(92.4%)

LP™

P

327

(98.5%)

322

(98.5%)

LP™

P

271

(97.5%)

262

(96.7%)

220

(93.6%)

201

(91.4%)

LP™

P

323

(97.6%)

310

(96.0%)

LP™

Cohort

P

211

(81.8%)

186

(88.2%)

182

(92.9%)

159

(87.4%)

LP™

P

257

(84.3%)

231

(89.9%)

LP™

Cohort

P

230

(90.6%)

219

(95.2%)

In addition to the study subjects described above, nineteen (19) subjects were consented but
declined participation in the study prior to receiving the assigned treatment. The demographic
and preoperative characteristics of the subjects who declined to participate in this study were
comparable to the patients included in this study.

Study Population Demographics and Baseline Parameters
Table 4 presents the summary statistics for demographic and baseline characteristics for the

Prestige LP™ IDE/PAS Cohort, the ACDF Control, and Prestige LP™ Safety Cohort. The
demographics of the study population are consistent with the demographics reported for prior
cervical artificial disc studies conducted in the U.S.

The investigational and control treatment groups were very similar demographically, and there
were no statistically significant differences (p<0.05) for any of the variables except for the use of
tobacco and race. Current tobacco use was higher in the control group (34.7% versus 26.4%) as
compared to the IDE/PAS Cohort. However, tobacco use was established through use of patient
questionnaires which utilized a binary response (i.e., yes or no), and quantification of the extent
or history of tobacco use was not established. Therefore, it is not possible to definitively
ascertain whether there were any substantial confounding effects from tobacco use on patient
outcomes. Regarding race differences among cohorts, there was a higher percentage of
Caucasian subjects in the IDE/PAS Cohort compared to the control group (96.8% versus 91.7%).

Table 4: Study Patient Demographics and Baseline Characteristics

Variables

Cohort

ACDF Control

(N=265)

Prestige LP™ Safety

Cohort (N=333)

(IDE/PAS vs.

LP™

C

P

275

-

(92.0%)

262

-

(95.3%)

1

Cumulative deaths are t he total number of deaths of stud y patients at th e 12, 24, 84 and 120-month tim e po i n ts . However, non e of th e

deaths were believed to be in any way related to the study treatment.

2

Expected = Theoretical minus Cumulative Deaths minus Cumulative Withdrawals minus Cumulative Lost Follow-Up

Medtronic Page 15 of 103

0.369

Height (inches)

67.7 ± 4.1

Range: 60.0 – 77.0

67.5 ± 4.2

Range: 58.0 – 80.0

67.7 ± 4.0

Range: 60.0 – 77.0

Weight (lbs.)

186.9 ± 45.0

Range: 100.0 – 340.0

184.7 ± 41.5

Range: 98.0 – 328.0

187.3 ± 45.2

Range: 100.0 – 340.0

BMI (kg/m2)

28.5 ± 5.6

Range: 17.2 – 48.2

28.3 ± 5.1

Range: 19.0 – 53.5

28.5 ± 5.6

Range: 17.2 – 48.2

Sex

Female (%)

151 (53.9%)

143 (54.0%)

178 (53.5%)

Race

Other

1 (0.4%)

1 (0.4%)

1 (0.3%)

Marital Status

Widowed

2 (0.7%)

2 (0.8%)

3 (0.9%)

Education Level

> High School

206 (74.1%)

173 (65.5%)

236 (71.3%)

Previous Neck Surgery

No

277 (98.9%)

263 (99.2%)

330 (99.1%)

Preoperative Medication use

Muscle Relaxants

100/279 (35.8%)

114/264 (43.2%)

123/332 (37.0%)

0.095

Preoperative Pain Status3

Neck Pain Only

25 (8.9%)

26 (9.8%)

34 (10.2%)

Worker’s Compensation

32/280 (11.4%)

35/365 (13.2%)

54/333 (16.2%)

0.602

Unresolved Spinal Litigation

34/280 (12.1%)

32/265 (12.1%)

61/333 (18.3%)

1.000

Current Tobacco Use

74/280 (26.4%)

92/265 (34.7%)

94/333 (28.2%)

0.041

Current Alcohol Use

150/280 (53.6%)

141/265 (53.2%)

172/333 (51.7%)

1.000

Preoperative Work Status

188/280 (67.1%)

166/265 (62.6%)

217/333 (65.2%)

0.282

Duration of S ymptoms

> 6 mos.

173 (61.8%)

161 (60.8%)

212 (63.7%)

0.622

0.567

0.722

Male (%)

Caucasian
Black
Asian
Hispanic

Single
Married
Divorced
Separated

< High School
High School

Yes

Non-Narcotics
Weak Narcotics
Strong Narcotics

Arm and Neck Pain
Arm Pain Only

129 (46.1%)

271 (96.8%)

7 (2.5%)
0 (0.0%)
1 (0.4%)

40 (14.3%)

189 (67.5%)

42 (15.0%)

7 (2.5%)

15 (5.4%)

57 (20.5%)

3 (1.1%)

208/280 (74.3%)
133/279 (47.7%)

62/279 (22.2%)

255 (91.1%)

0 (0.0%)

122 (46.0%)

243 (91.7%)

13 (4.9%)

2 (0.8%)
6 (2.3%)

32 (12.1%)

204 (77.0%)

24 (9.1%)

3 (1.1%)

14 (5.3%)

77 (29.2%)

2 (0.8%)

187/263 (71.1%)
127/263 (48.3%)

58/264 (22.0%)

238 (90.2%)

0 (0.0%)

155 (46.5%)

320 (96.1%)

10 (3.0%)

1 (0.3%)
1 (0.3%)

47 (14.1%)

224 (67.3%)

51 (15.3%)

8 (2.4%)

17 (5.1%)

78 (23.6%)

3 (0.9%)

246/333 (73.9%)
152/332 (45.8%)

68/332 (20.5%)

299 (89.8%)

0 (0.0%)

1.000

0.043

0.096

0.062

1.000

0.441

0.931

1.000

0.769

< 6 wks.
6 wks. – 6 mos.

The mean baseline pre-operative assessments for the Prestige LP™ IDE/PAS Cohort, Control
Group, and Prestige LP™ Safety Cohort are presented in Table 5. There were no statistical
differences between the Prestige LP™ IDE/PAS Cohort and Control for NDI, SF-36 PCS, SF-36
MCS, neck pain, and arm pain. There were statistically significant differences in baseline motor
neurologic status (38.2% - Prestige LP™ IDE/PAS Cohort; 59.5% - Control) and mean cervical
range of motion (5.67º - Prestige LP™ IDE/PAS Cohort; 7.87º - Control). However, after

3

Arm pain is defined as a subject having an arm pain score ≥20 and neck pain is defined as a subject having a neck pain score

≥20. If a subject has both an arm pain score ≥20 and a neck pain score ≥20, then this subject is considered as having “Arm and
Neck Pain”; if a subject has a neck pain score ≥20 and an arm pain score < 20, then this subject is considered as having “Neck
Pain Only”; if a subject has an arm pain score ≥20 and a neck pain score < 20, then this subject is considered as having “Arm
Pain Only”. Since neck pain score ≥20 is an inclusion criteria, there are no subjects with “Arm Pain Only”.

Cervical Disc is indicated in skeletally mature patients for reconstruction of the disc at one level from C3-C7 following single­level discectomy for in tractable radiculopathy ( arm pain and/or a neurological deficit) with or without neck pain and is not
indicated for treatment of isolated neck pain. No patients were included into the study with neck pain without any other
symptoms.

Medtronic Page 16 of 103

22 (7.9%)

85 (30.4%)

15 (5.7%)

89 (33.6%)

24 (7.2%)

97 (29.1%)

0.494

The Prestige LP™

p-value (IDE/PAS

Control)

55.5 ± 14.7

Range: 30.0 – 98.0

56.4 ± 15.9

Range: 26.0 – 100.0

56.6 ± 15.0

Range: 30.0 – 98.0

32.2 ± 7.4

Range: 14.3 – 57.9

32.0 ± 7.5

Range: 7.9 – 56.0

32.3 ± 7.1

Range: 14.3 – 57.9

44.5 ± 11.5

Range: 16.5 – 68.3

42.7 ± 12.4

Range: 14.1 – 70.8

43.8 ± 11.9

Range: 16.5 – 68.3

67.0 ± 20.8

Range: 20.0 – 100.0

69.3 ± 21.5

Range: 20.0 – 100.0

68.0 ± 20.8

Range: 20.0 – 100.0

59.6 ± 26.3

Range: 0.0 – 100.0

62.4 ± 28.5

Range: 0.0 – 100.0

59.0 ± 27.1

Range: 0.0 – 100.0

• Overall4

64/280 (22.9%)

79/264 (29.9%)

73/333 (21.9%)

0.065

5.67 ± 3.69

Range: 0.27 – 18.10

7.87 ± 4.32

Range: 0.74 – 21.34

5.88 ± 3.78

Range: 0.27 – 19.47

0.26 ± 0.25

Range: 0.00 – 1.64

Posterior Mean and 95% BCI5 of the

(lower, upper)

Spinal Level Treated

C34 (%)

4 (1.4%)

10 (3.8%)

4 (1.2%)

N/A

C45 (%)

21 (7.5%)

15 (5.7%)

28 (8.4%)

N/A

C56 (%)

147 (52.5%)

149 (56.2%)

178 (53.5%)

N/A

C67 (%)

108 (38.6%)

91 (34.3%)

123 (36.9%)

N/A

Operative time (hrs)

1.5 ± 0.6

(n=280)

1.4 ± 0.5

(n=265)

1.4 ± 0.5

(n=333)

propensity score adjustments, the variables appeared balanced between groups. Thus, differences
in baseline symptoms were adjusted for in the analysis and are therefore unlikely to have led to
significant bias in the reported results.

Table 5: Preoperative Evaluation of Endpoints

Variables

NDI

SF-36 PCS

SF-36 MCS

Neck Pain Score

Arm Pain Score

Prestige LP™ IDE/PAS Cohort

(N=280)

ACDF Control

(N=265)

Prestige LP™ Safety Cohort

(N=333)

Cohort vs ACDF

0.498

0.777

0.079

0.191

0.236

Neurological Status (normal)

• Motor

• Sensory

• Reflexes

Baseline ROM angulation (º)

Baseline ROM translation (mm) N/A

107/280 (38.2%)
117/280 (41.8%)
186/280 (66.4%)

157/264 (59.5%)
134/264 (50.8%)
161/264 (61.0%)

135/333 (40.5%)
147/333 (44.1%)
200/333 (60.1%)

N/A N/A

< 0.001

0.039

0.212

< 0.001

Surgery and Hospitalization
Table 6 summarizes the information related to the surgical procedures and postoperative

hospitalizations of subjects. The most common treated surgical levels were C5-C6 and C6-C7.
The mean operative times for the IDE/PAS and control treatment groups were 1.5 hours and 1.4
hours, respectively, which is a mean difference of 0.1 hours, or 6 minutes and is unlikely to
represent any significant clinical difference. Additionally, investigational subjects were found to
have similar estimated blood loss to the control group subjects (50.5 ml for IDE/PAS cohort and

49.4 ml for Safety cohort versus 57.5 ml for control group). The median blood loss was 35 ml for
the IDE/PAS cohort versus 50 ml for both the Safety and control groups. The mean hospital
stays of subjects in all treatment groups were similar (1.0 days for all groups). Table 7
summarizes the Prestige LP™ device implanted by size and level.

Table 6: Surgical Data

Prestige LP™

IDE/PAS Cohort

(N=280)

ACDF Control

(N=265)

Prestige LP™ Safety

Cohort

(N=333)

Difference of Mean between IDE/PAS

Cohort and Control Group

4

If at least one of the three components (motor, sensory, reflexes) is not normal, then overall is defined as “not normal”, if all the

components are nor mal, then overall is defined as “normal”

5

BCI = Bayesian HPD Credible Interval

Medtronic Page 17 of 103

Range: 0.7 – 3.4

Range: 0.6 – 3.4

Range: 0.7 – 3.4

0.11 (0.02, 0. 22)

Blood Loss (m l)

50.5 ± 73.5

(n=278)

57.5 ± 68.1

(n=263)

49.4 ± 67.9

(n=333)

Hospitaliz ation (days)

1.0 ± 0.5

(n=280)

1.0 ± 0.5

(n=265)

1.0 ± 0.4

(n=333)

Median Return to Work
Time (days)

6mm x 12mm Disc (%)

6mm x 14mm Disc (%)

132

(39.6%)

6mm x 16mm Disc (%)

6mm x 18mm Disc (%)

7mm x 12mm Disc (%)6

7mm x 14mm Disc (%)

7mm x 16mm Disc (%)

7mm x 18mm Disc (%)

8mm x 12mm Disc (%)

8mm x 14mm Disc (%)

8mm x 16mm Disc (%)

8mm x 18mm Disc (%)

4

(1.4%)

21

(7.5%)

147

(52.5%

108

(38.6%)

280

(100.0%)

4

(1.2)

28

(8.4%)

178

(53.5%)

123

(36.9%)

333

(100.0%)

Range: 3.0 – 700.0

Median: 35.0

Range: 0.0 – 3.0

40 61 42 N/A

Range: 0.0 – 700.0

Median: 50.0

Range: 0.0 – 4.0

Range: 3.0 – 700.0

Median 50.0

Range: 0.0 – 3.0

-4.7 (-16.8, 7.9)

0.03 (-0.0 5, 0. 11)

Table 7: All Prestige LP™ Devices Implanted by Size and Level

Prestige LP™ IDE/PAS Cohort Prestige LP™ Safety Cohort
C3-C4 C4-C5 C5-C6 C6-C7 Total C3-C4 C4-C5 C5-C6 C6-C7 Total

1 4 15 11 31 (11.1%) 1 8 28 12 49(14.7%)
1 10 65 37 113 (40.4%) 1 13 76 42
2 1 35 23 61 (21.8%) 2 1 37 23 63 (18.9%)

0 0 0 0 0 (0.0%) 0 0 0 0 0 (0.0%)
0 0 1 1 2 (0.7%) 0 0 1 2 3 (0.9%)
0 2 5 8 15 (5.4%) 0 2 9 11 22 (6.6%)
0 4 16 9 29 (10.4%) 0 4 17 12 33 (9.9%)
0 0 9 11 20 (7.1%) 0 0 9 11 20 (6.0%)
0 0 0 0 0 (0.0%) 0 0 0 0 0 (0.0%)
0 0 0 3 3 (1.1%) 0 0 0 4 4 (1.2%)
0 0 1 4 5 (1.8%) 0 0 1 5 6 ( 1.8%)
0 0 0 1 1 (0.4%) 0 0 0 1 1 (0.3%)

Total (%)

SUMMARY OF THE IDE AND POST-APPROVAL STUDY (PAS) RESULTS

Final Safety Findings (Key Endpoints)

The analysis of safety was based on the as-treated cohort of 598 total patients with surgery (333
Prestige LP™ “Safety” subjects consisting of 280 Prestige LP™ IDE/PAS Cohort subjects, as
well as 54 subjects from the Continued Access (CA) and Metal Ion (MI) Cohorts7; and 265
ACDF control subjects). This was a non-randomized study and the ACDF group was a historical
control. A summary of the total number of adverse events (AE) is shown in Table 8. Adverse
events were classified by the independent Clinical Adjudication Committee (CAC) for severity
and relationship to the device and/or surgical procedure.

6

The 7mm x 12mm Prestige LP™ Cervical Disc was a part of the size offerings in the IDE/PAS study, but is not a part

of the size offerings available for market.

7

One Metal Ion Cohort subject was also an IDE Cohort s ubject.

Medtronic Page 18 of 103

Posterior

Control9

Patients (%)

257 (91.8%)

219 (82.6%)

307 (92.2%)

271 (96.8%)

232 (87.5%)

323 (97.0%)

275 (98.2%)

327 (98.2%)

Events
(Events/Patient)

Device or

Patients (%)

73 (26.1%)

69 (26.0%)

80 (24.0%)

75 (26.8%)

70 (26.4%)

83 (24.9%)

75 (26.8%)

83 (24.9%)

Table 8: Summary of Adverse Events Up to the 120 Month Time Interval

IDE 24 Month PAS 84 Month PAS 120 Month

Adverse Event

Type

All Adverse
Events (AEs)

Device/Surgical
Procedure Related
AEs

Surgical
Procedure Related
AEs Only

Severe Adverse
Events
(Grade 3 or 4)

Severe Device or
Device/Procedure

-Related AEs
(Grade 3 or 4)

Prestige

Measure

Patients (%) 34 (12.1%) 41 (15.5%) 41 (12.3%)

Events
(Events/Patient)

Events
(Events/Patient)

Patients (%) 126 (45.0%) 96 (36.2%) 157 (47.1%)
Events

(Events/Patient)
Patients (%) 13 (4.6%)

Events
(Events/Patient)

LP™

IDE Cohort

(N=280)

1581 (5.65) 1225 (4.62) 1901 (5.71) 2774 (9.91) 2236 (8.44) 3384 (10.16) 3523 (12.58) 4276 (12.84)

66 (0.24) 73 (0.28) 76 (0.23) 99 (0.35) 86 (0.32) 114 (0.34) 114 (0.41) 135 (0.41)

141 (0.50) 117 (0.44) 148 (0.44) 144 (0.51) 118 (0.45) 152 (0.46) 144 (0.51) 152 (0.46)

409 (1.46) 257 (0.97) 500 (1.50) 762 (2.72) 507 (1.91) 955 (2.87) 1025 (3.66) 1258 (3.78)

33 (0.12)

31 (0.12) 33 (0.10) 48 (0.17) 31 (0.12) 48 (0.14) 54 (0.19) 54 (0.16)

ACDF
Control
(N=265)

14 (5.3%) 13 (3 .9% ) 17 (6.1%) 14 (5.3%) 17 (5.1%)

Prestige

LP™

Safety

Cohort

(N=333)

Mean and

95% BCI8 of

the

Difference of

Event Rate

between IDE

Cohort and

ACDF

10.2%

(4.3%, 16.4%)

-3.0%

(-9.5%, 3.0%)

0.8%

(-7.6%, 8.3%)

10.6%

(1.4%, 19.4%)

Prestige

LP™

PAS Cohort

(N=280)

49 (17.5%) 44 (16.6%) 61 (18.3%)

174 (62.1%) 139 (52.5%) 215 (64.6%)

ACDF
Control
(N=265)

Prestige

LP™

Safety

Cohort

(N=333)

Posterior M ean

and 95% BCI10 of

the Difference of

Event Rate

between PAS

Cohort and ACDF

Control11

9.0%

(4.2%, 13.9%)

1.7%

(-5.3%, 8.8%)

0.9%

(-6.7%, 9.5%)

8.1%

(-1.3%, 16.9%)

0.9%

(-3.2%, 5.2%)

Prestige

LP™

PAS Cohort

(N=280)

56 (20.0%) 73 (21.9%)

191 (68.2%) 236 (70.9%)

21 (7.5%) 21 (6.3)

Prestige LP™
Safety Cohort

(N=333)

8

BCI = Bayesian HPD Credible Interval

9

95% BCI of the difference of the event rate between the investigational group and control group was only determined for the “All Adverse Events” category because the analysis

was pre-defined. All other analyses were not pre-defined.

10

BCI = Bayesian HPD Credible Interval

11

95% BCI of the difference of the event rate between the investigational group and control group was only determined for the “All Adverse Events” category because the anal ysis

was pre-defined. All other analyses were not pre-defined.

Medtronic Page 19 of 103

Level

(N=280)

(N=265)

(N=333)

Point Estimate

Cohort

(N=280)

(N=265)

(N=333)

Point Estimate

Cohort

4/4

(100%)

9/10

(90.0%)

4/4

(100.0%)

10.0%

(-19.9%, 39.9 % )

4/4

(100%)

9/10

(90.0%)

4/4

(100.0%)

10.0%

(-19.9%, 39.9 % )

20/21

(95.2%)

12/15

(80.0%)

27/28

(96.4%)

15.2%

(-5.6%, 36.1%)

21/21

(100%)

12/15

(80.0%)

28/28

(100.0%)

20.0%

(1.7%, 38.3%)

135/147
(91.8%)

124/149
(83.2%)

163/178
(91.6%)

8.6%

(1.1%, 16.2%)

142/147
(96.6%)

131/149
(87.9%)

172/178
(96.6%)

8.7%

(2.6%, 14.8%)

98/108

(90.7%)

74/91

(81.3%)

112/123
(91.1%)

9.4%

(-0.1%, 19.0%)

104/108
(96.3%)

80/91

(87.9%)

119/123
(96.7%)

8.4%

(1.0%, 15.7%)

Table 9 provides summary data on the number of adverse events in each treatment group by
treatment level, including post-hoc statistical analysis and comparison between the Prestige LP™
IDE/PAS Cohort and the ACDF control group through the 24- and 84- month time points using
Frequentist methods. The percentage of subjects with adverse events was not statistically
different between the two groups at 24 months for all levels except for C5-C6; however, this
difference was not clinically meaningful. The percentage of subjects with adverse events was
statistically different between the two groups at 84 months for all levels except for C3-C4.

Table 9: Summary of Total Adverse Events by Level Treated through Month 24 IDE and

84 PAS and Safety Population

IDE 24 Month PAS 84 Month

Treatment

C3-C4

C4-C5

C5-C6

C6-C7

Prestige

LP™

IDE

Cohort

ACDF

Control

Prestige

LP™

Safety

Cohort

and 95%

Confidence

Interval12 of
Difference of
Adverse Rate
between IDE

Cohort and

ACDF Control

Prestige

LP™

IDE Cohort

ACDF

Control

Prestige

LP™

Safety

Cohort

and 95%

Confidence

Interval13 of

Difference of

Adverse Rate

between IDE

Cohort and

ACDF Control

Tables 10a and 10b report adverse events from all patients to establish the safety profile of the

device. Tables 10c to 10e report adverse events classified as device related or device/surgical
procedure-related. Adverse events are listed in alphabetical order. Adverse event rates are based
on the number of patients having at least one occurrence of an adverse event, divided by the
number of patients in that treatment group. Subjects experiencing adverse events in more than
one category are represented in each category in which they experienced an adverse event.

24 Months The overall adverse event rate was higher for subjects treated with the Prestige LP™ device (IDE Cohort, 91.8%; Safety Cohort, 92.2%) compared to the Control (82.6%) through 24 months. At 24 months, the adverse event rate between the Prestige LP™ IDE Cohort and the Control was statistically different with the 95% BCI for the difference of adverse events rates between the Prestige LP™ IDE Cohort and the ACDF Control Cohort being (4.3%, 16.4%), excluding 0. However, when comparing device-related adverse events, the rates are comparable. Although the rate of Prestige LP™ IDE subjects having at least one adverse event was statistically higher than the control group rate, the difference in adverse event rates was not considered to be clinically meaningful and this finding may be attributable to the higher follow-up rates (and potentially, higher reporting of events) for investigational subjects as compared to the ACDF control subjects. Specifically, note that the 24-month follow-up rates are 97.8% and 96.6% respectively

12

The 95% CI was provided using Fr e que ntist Farringt on a nd Ma nning methods

13

The 95% CI was provided using Frequentist Farrington and Manning methods

Medtronic Page 20 of 103

for the Prestige LP™ IDE Cohort and ACDF Control Cohort. Table 11 lists the brief definitions
for all adverse events.

84 Months The overall adverse event rate was higher for subjects treated with the Prestige LP™ device (PAS Cohort, 96.8%; Safety Cohort, 97.0%) compared to the Control (87.5%) through 84 months. This included a higher cumulative rate for the categories of vascular AE (8.6% vs 3.0%) through 84 months. At 84 months, the adverse event rate between the Prestige LP™ PAS Cohort and the Control was statistically different with the 95% BCI for the difference of adverse events rates between the Prestige LP™ PAS Cohort and the ACDF Control Cohort being (4.2%,

13.9%), excluding 0. The conclusion of Bayesian analysis remains similar with the results of
time-to-event analyses.

120 Months The overall adverse event rate for subjects treated with the Prestige LP™ device was PAS Cohort, 98.2% and Safety Cohort, 98.2 through 120 months.

Regarding the vascular AE rates, more investigational subjects had Grade 3 or 4 vascular events
than control subjects (cumulative rate: 5.3% vs. 0.5%). However, none of these vascular events
was implant- or implant/surgical procedure-related according to the judgement determined by the
adjudication committee. Thirty-three vascular events were reported in the investigational group
for up to 120 months. Four of these events were surgical procedure-related and included bleeding
and excessive blood loss. These events are expected risks associated with any surgical procedure.
The remaining events were not related to the procedure nor the device. These events included
heterogenous pathologies such as occlusion, insufficiency, aneurysm, vascular leak, blood clots,
thrombosis, bleeding ulcer, vascular stenosis, and Raynaud’s disease. Case histories of those
events demonstrated various causes and/or risk factors such as trauma, hereditary disease,
hypertension, hypercholesterolemia, diabetes, gastrointestinal disorder, thyroid diseases,
arrhythmia, and cancer.

Prior to 24 months, two deaths occurred in the control group and none in the investigational
group. There were three deaths in the investigational group and five deaths in the control group
by 84 months. By 120 months, four deaths occurred in the investigational group. Deaths were
evaluated based upon available information and none of the deaths were believed to be in any
way related to the study treatment.

Medtronic Page 21 of 103

Mos)

Prestige LP™ Safety

Prestige LP™ Safety

ANATOMICAL/TECH
NICAL DIFFICULTY

2 (0.7) 2 0 (0.0) 0 2 (0.6)

2

2 (0.7) 2 0 (0.0) 0 2 (0.6)

2

0 (0.0) 0 0 (0.0) 0 0 (0.0)

0

3 (1.1) 5 2 (0.8) 2 5 (1.5)

7

15 (5.4)

22

18 (6.8)

20

26

0 (0.0) 0 3 (1.1) 3 0 (0.0)

0

DYSPHAGIA/
DYSPHONIA

26 (9.3)

31

22 (8.3)

24

29 (8.7)

35

21 (7.5)

23

22 (8.3)

24

23 (6.9)

26

8 (2.9) 8 0 (0.0) 0 9 (2.7)

9

33 (11.8)

55

39 (14.7)

69

42 (12.6)

69

HETEROTOPIC
OSSIFICATION

20 (7.1)

23

17 (6.4)

22

24 (7.2)

27

15 (5.4)

18

17 (6.4)

21

19 (5.7)

22

5 (1.8) 5 1 (0.4) 1 5 (1.5)

5

15 (5.4)

15

5 (1.9) 5 20 (6.0)

20

2 (0.7) 2 3 (1.1) 3 2 (0.6)

2

6 (2.1) 6 0 (0.0) 0 6 (1.8)

6

Displacement-

Subsidence

2 (0.7) 2 0 (0.0) 0 7 (2.1)

7

0 0 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0

0 (0.0)

2 (0.8)

0 (0.0)

Adverse Events

Total Adverse Events

Cervical-Study Surgery

Non-Cervical

CANCER
CARDIAC

DISORDERS
DEATH

Dysphagia

Dysphonia

GASTROINTESTINAL

Cervical

Non-Cervical

IMPLANT EVENTS

Breakage

Displacement

Loosening

14, 15

24 Months

(≥19 Mos- <30

ACDF Control

Prestige LP™ IDE Cohort

Surgery

Prestige LP™ IDE Cohort

Table 10a: Adverse Events in Pivotal Study Through 24 Months

Postoperative

(1 day - <4 Wks)

ACDF Control16

Prestige LP™ Safety Cohort

ACDF Control

Prestige LP™ IDE Cohort

6 Weeks

(≥4 Wks - <9 Wks)

Prestige LP™ IDE Cohort

Prestige LP™ Safety Cohort

3 Months

(≥9 Wks - <5 Mos)

Cohort

ACDF Control

ACDF Control

Prestige LP™ IDE Cohort

(≥5 Mos- <9 Mos)

Prestige LP™ Safety Cohort

6 Months

Prestige LP™ IDE Cohort

12 Months

(≥9 Mos- <19 Mos)

ACDF Control

Prestige LP™ Safety Cohort

ACDF Control

Prestige LP™ IDE Cohort

Prestige LP™ Safety Cohort

29 34 35 173 119 188 179 97 235 241 211 301 246 143 304 401 280 465 312 341 373

2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 1 1 1 0 0 0 0 0 0 1 0 1 3 0 3 0 1 2

0 0 0 2 2 2 2 1 4 0 2 0 2 3 2 5 3 6 11 9 12

0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 1 0 0 1 0
1 5 1 15 11 16 4 4 6 5 3 5 4 0 4 0 1 0 2 0 3

1 5 1 11 11 11 3 4 5 3 3 3 3 0 3 0 1 0 2 0 3

0 0 0 4 0 5 1 0 1 2 0 2 1 0 1 0 0 0 0 0 0

2 7 2 8 7 8 1 3 2 3 4 6 3 3 7 20 21 22 18 24 22
0 0 0 2 1 2 6 4 6 2 2 2 4 1 5 3 3 5 6 11 7

0 0 0 2 1 2 4 4 4 2 2 2 4 1 5 2 3 4 4 10 5

0 0 0 0 0 0 2 0 2 0 0 0 0 0 0 1 0 1 2 1 2

6 0 6 1 1 1 2 1 3 2 0 2 0 0 2 0 2 1 4 1 5
2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 1 0

0 0 0 1 0 1 1 0 1 2 0 2 0 0 0 0 0 0 2 0 2

0 0 0 0 0 0 1 0 2 0 0 0 0 0 2 0 0 1 1 0 2

Total (Up to 24 Mos)

# of Patients Reporting & Total

adverse events

Cohort

Total # Events

#Patients (% of 280)

Prestige LP™ IDE Cohort

257 (91.8)

1581

219 (82.6)

ACDF Control

1225

Total # Events

#Patients (% of 265)

#Patients (% of 333)

Prestige LP™ Safety Cohort

307 (92.2)

1901

18 (5.4)

Total # Events

14

Based on 24-month cohort.

15

Some adverse events may lead to additional surgeries or interventions. Refer to Table 4 for more information.

16

Control=Single-level anterior interbody fusion procedure with allograft and plate stabilization. Non-randomized control arm from IDE study of Prestige™ Cervical Disc.

Medtronic Page 22 of 103

0 2 0

5 (1.8) 5 0 (0.0) 0 5 (1.5)

5

0 (0.0) 0 0 (0.0) 0 0 (0.0)

0

33 (11.8)

52

27 (10.2)

37

39 (11.7)

59

Deep Surgical Site

(Below Fasciae)-Cervical

0 (0.0) 0 1 (0.4) 1 0 (0.0)

0

31 (11.1)

46

22 (8.3)

30

35 (10.5)

50

0 (0.0) 0 1 (0.4) 1 1 (0.3)

1

Superfical Surgical Site

Cervical

0 (0.0) 0 0 (0.0) 0 0 (0.0)

0

3 (1.1) 3 1 (0.4) 1 5 (1.5)

5

NECK AND/OR ARM
PAIN

158 (56.4)

339

125 (47.2)

226

197 (59.2)

425

83 (29.6)

112

71 (26.8)

84

101 (30.3)

141

47 (16.8)

71

26 (9.8)

29

58 (17.4)

89

100 (35.7)

151

76 (28.7)

109

126 (37.8)

189

Neck Pain

(Non-Cervical)

5 (1.8) 5 4 (1.5) 4 6 (1.8)

6

114 (40.7)

199

106 (40.0)

219

134 (40.2)

238

20 (7.1)

20

11 (4.2)

13

26 (7.8)

26

4 (1.4) 4 5 (1.9) 6 4 (1.2)

4

6 (2.1) 6 6 (2.3) 6 6 (1.8)

6

Lower Extremity-

Sensory

14 (5.0)

18

20 (7.5)

27

15 (4.5)

20

43 (15.4)

51

30 (11.3)

40

50 (15.0)

59

0 (0.0) 0 0 (0.0) 0 0 (0.0)

0

Upper And Lower

Extremity-Motor

2 (0.7) 2 2 (0.8) 2 2 (0.6)

2

Upper And Lower

Extremity-Sensory

6 (2.1) 6 8 (3.0)

10

7 (2.1)

7

8 (2.9) 8 9 (3.4) 9 10 (3.0)

11

Upper Extremity-

61 (21.8)

84

67 (25.3)

106

73 (21.9)

103

1 (0.4) 1 33 (12.5)

34

1 (0.3)

1

91 (32.5)

174

82 (30.9)

131

111 (33.3)

208

142 (50.7)

274

129 (48.7)

225

170 (51.1)

325

37 (13.2)

44

34 (12.8)

37

46 (13.8)

55

Malpositioning

Other

INFECTION

Other Infection

Other Wound

(Skin To Fasciae)-

Systemic Infection

Urinary Tract Infection

Arm Pain (Cervical)

Arm Pain (Non-Cervical)

Neck Pain (Cervical)

NEUROLOGICAL

Carpal Tunnel Syndrome

Gait Disturbance

Lower Extremity-Motor

Non-Specific Or Other

Spinal Cord Disturbance

Upper Extremity-Motor

Sensory

NON-UNION

OTHER

OTHER PAIN

Back Pain

4 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

1 2 1 5 3 5 5 5 6 6 2 10 10 1 11 14 10 14 11 14 12

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0

1 2 1 3 1 3 5 2 6 6 2 8 9 1 9 13 8 13 9 14 10
0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0

0 0 0 1 1 1 0 3 0 0 0 0 1 0 1 0 0 0 1 0 1

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 1 1 1 0 0 0 0 0 2 0 0 0 1 0 1 1 0 1
3 2 4 35 18 37 54 19 76 70 49 90 52 42 66 76 55 92 49 41 60

2 1 3 15 9 16 13 9 22 22 22 27 20 10 24 26 18 31 14 15 18

0 0 0 2 2 2 12 2 16 15 6 20 14 4 17 12 10 16 16 5 18

1 1 1 17 7 18 29 8 38 32 21 42 18 25 25 36 27 42 18 20 23
0 0 0 1 0 1 0 0 0 1 0 1 0 3 0 2 0 3 1 1 1

2 6 2 14 24 16 23 18 29 36 36 42 24 17 31 69 57 81 31 61 37

0 0 0 1 1 1 1 3 1 3 1 4 5 1 6 8 3 10 2 4 4
0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 3 4 3 1 0 1

0 0 0 1 0 1 0 0 0 0 0 0 2 2 2 3 1 3 0 3 0

1 0 1 3 2 4 1 1 1 1 10 2 3 1 3 5 4 5 4 9 4

1 2 1 4 6 4 6 7 7 3 5 5 6 4 8 22 7 24 9 9 10
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 2 0 1 0 1

0 0 0 0 0 0 1 1 1 1 5 1 0 1 0 3 2 3 1 1 2

0 2 0 0 2 0 1 0 2 4 0 4 1 1 1 1 3 3 1 1 1
0 2 0 5 13 6 13 6 17 23 15 25 7 5 11 24 31 30 12 34 14

0 0 0 0 0 0 0 3 0 0 4 0 1 9 1 0 9 0 0 9 0

4 3 7 19 14 22 14 13 15 23 17 27 29 10 39 56 20 62 29 54 36

4 6 4 19 19 20 33 10 38 48 44 64 53 28 65 69 58 77 48 60 57
0 1 0 0 1 0 7 1 9 11 11 16 12 8 13 10 6 13 4 9 4

3 (1.1)

3

4 (1.5)

4

3 (0.9)

3

Medtronic Page 23 of 103

53 (18.9)

65

36 (13.6)

40

66 (19.8)

80

10 (3.6)

10

7 (2.6) 7 12 (3.6)

12

102 (36.4)

155

92 (34.7)

141

121 (36.3)

178

24 (8.6)

34

17 (6.4)

23

27 (8.1)

39

93 (33.2)

195

58 (21.9)

114

119 (35.7)

240

Cervical-Non-Study

Surgery

44 (15.7)

71

31 (11.7)

58

57 (17.1)

93

27 (9.6)

36

12 (4.5)

15

33 (9.9)

42

45 (16.1)

88

27 (10.2)

41

54 (16.2)

105

65 (23.2)

76

35 (13.2)

44

75 (22.5)

88

26 (9.3)

40

9 (3.4)

11

32 (9.6)

46

12 (4.3)

13

3 (1.1) 3 13 (3.9)

14

3 (1.1) 3 1 (0.4) 1 4 (1.2)

4

9 (3.2)

10

2 (0.8) 2 9 (2.7)

10

WOUND (NON­INFECTIOUS)

21 (7.5)

31

13 (4.9)

13

22 (6.6)

32

1 (0.4) 1 1 (0.4) 1 1 (0.3)

1

5 (1.8) 5 1 (0.4) 1 5 (1.5)

5

6 (2.1) 6 3 (1.1) 3 6 (1.8)

6

12 (4.3)

19

8 (3.0) 8 13 (3.9)

20

Lower Extremity Pain

RESPIRATORY

SPINAL EVENT

Cervical-Study Surgery

Non-Cervical

TRAUMA

UROGENITAL

VASCULAR

Injury Intra-Operative

Dehiscence

Headache

Other

Other

Csf Leak

Hematoma

Other

1 2 1 5 3 5 12 3 14 11 7 13 8 2 12 18 11 22 10 12 13

0 0 0 1 0 1 1 1 1 0 2 1 2 1 3 4 0 4 2 3 2
3 3 3 13 15 14 13 5 14 26 24 34 31 17 37 37 41 38 32 36 38

0 0 0 8 4 8 0 4 1 1 1 1 11 5 11 1 1 4 13 8 14

0 0 0 22 8 26 25 6 38 26 30 32 26 15 32 52 22 61 44 33 51

0 0 0 10 3 11 13 3 20 11 12 14 9 7 14 13 11 18 15 22 16
0 0 0 9 2 9 9 1 10 3 6 4 5 0 5 5 1 6 5 5 8

0 0 0 3 3 6 3 2 8 12 12 14 12 8 13 34 10 37 24 6 27

0 0 0 6 2 8 5 4 6 13 12 14 12 5 13 20 9 23 20 12 24

1 0 1 1 0 1 2 0 2 1 1 1 8 3 8 11 5 12 16 2 21
3 1 4 1 0 1 1 0 1 1 1 1 2 0 2 0 1 0 5 0 5

3 1 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 1 0 1 1 0 1 1 1 1 2 0 2 0 1 0 5 0 5

0 2 1 14 4 14 2 2 2 4 2 4 4 1 4 2 2 2 5 0 5
0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 1

0 0 0 3 1 3 0 0 0 0 0 0 0 0 0 1 0 1 1 0 1

0 0 0 2 3 2 1 0 1 1 0 1 0 0 0 1 0 1 1 0 1
0 1 1 9 0 9 1 2 1 3 2 3 4 1 4 0 2 0 2 0 2

Medtronic Page 24 of 103

Prestige LP™

Total # Events

Prestige LP™ Safety C

ANATOMICAL/

DIFFICULTY

2 (0.7) 2 0 (0.0) 0 2 (0.6) 2 2 (0.7)

2

2 (0.6)

2

1 (0.4) 1 0 (0.0) 0 1 (0.3) 1 1 (0.4)

1

1 (0.3)

1

6 (2.1)

12

5 (1.9) 5 9 (2.7)

15

10 (3.6)

21

14 (4.2)

27

61

46

74

94

107

2 (0.7) 2 5 (1.9) 5 3 (0.9) 3 3 (1.1)

3

4 (1.2)

4

DYSPHAGIA/
DYSPHONIA

31 (11.1)

37

26 (9.8)

31

36 (10.8)

44

33 (11.8)

40

38 (11.4)

47

25 (8.9)

27

26 (9.8)

30

28 (8.4)

32

26 (9.3)

29

29 (8.7)

34

10 (3.6)

10

1 (0.4) 1 12 (3.6)

12

11 (3.9)

11

13 (3.9)

13

64 (22.9)

140

64 (24.2)

120

80 (24.0)

176

74 (26.4)

190

93 (27.9)

241

HETEROTOPIC

44 (15.7)

52

34 (12.8)

44

56 (16.8)

65

50 (17.9)

65

68 (20.4)

89

37 (13.2)

42

31 (11.7)

36

45 (13.5)

51

39 (13.9)

47

53 (15.9)

63

10 (3.6)

10

7 (2.6) 8 14 (4.2)

14

16 (5.7)

18

22 (6.6)

26

20 (7.1)

22

9 (3.4)

11

27 (8.1)

29

24 (8.6)

28

31 (9.3)

35

3 (1.1) 4 5 (1.9) 5 3 (0.9) 4 4 (1.4)

5

4 (1.2)

5

6 (2.1) 6 0 (0.0) 0 6 (1.8) 6 7 (2.5)

7

7 (2.1)

7

Displacement-

Subsidence

6 (2.1) 6 1 (0.4) 1 12 (3.6)

12

7 (2.5)

7

13 (3.9)

13

0 (0.0) 0 4 (1.5) 5 0 (0.0) 0 0 (0.0)

0

0 (0.0)

0

Adverse Events

Total Adverse Events

TECHNICAL

Cervical-Study Surgery

Non-Cervical

CANCER
CARDIAC

DISORDERS
DEATH

Dysphagia

Dysphonia

GASTROINTESTINAL

OSSIFICATION

Cervical

Non-Cervical

IMPLANT EVENTS

Breakage

Displacement

Loosening

Table 10b: Adverse Events in Pivotal Study Through 120 Months

36 Months

(≥30 Mos - < 42 Mos)

ACDF Control

Prestige LP™ PAS Cohort

Prestige LP™ Safety Cohort

328 235 396 218 256 298 300 251 355 222 153 269 125 116 165

0 0 0 0 0 0 1 0 1 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 1 0 1 0 0 0 0 0 0

4 1 4 0 0 0 2 1 2 0 1 1 1 0 1

6 7 9 8 5 13 11 5 11 8 6 8 6 3 7

0 0 0 0 2 0 2 0 2 0 0 1 0 0 0

5 0 5 1 3 2 0 4 0 0 0 0 0 0 2

3 0 3 1 2 1 0 4 0 0 0 0 0 0 2
2 0 2 0 1 1 0 0 0 0 0 0 0 0 0

19 8 25 19 16 24 23 12 28 20 9 23 4 6 7

5 3 7 5 8 6 6 5 10 5 3 5 8 3 10

4 2 4 5 5 6 4 4 6 5 1 5 6 3 8
1 1 3 0 3 0 2 1 4 0 2 0 2 0 2

1 1 2 1 0 1 4 4 5 0 1 0 1 0 1

0 1 0 1 0 1 1 1 1 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
1 0 2 0 0 0 2 1 2 0 0 0 1 0 1

0 0 0 0 0 0 0 2 0 0 1 0 0 0 0

48 Months

(≥42 Mos - < 54 Mos)

ACDF Control

Prestige LP™ PAS Cohort

(≥54 Mos - < 66 Mos)

Safety Cohort

Prestige LP™ PAS Cohort

60 Weeks

ACDF Control

(≥66 Mos - < 78 Mos)

Prestige LP™ Safety Cohort

72 Months

Prestige LP™ PAS Cohort

84 Months

(≥78 Mos - < 90 Mos)

ACDF Control

Prestige LP™ Safety Cohort

ACDF Control

Prestige LP™ PAS Cohort

Total (Up to 84 Months) # of Patients

Reporting & Total adverse events

Total # Events

ACDF Control

232 (87.5)

2236

0 (0.0)

37 (14.0)

Prestige LP™ Safety Cohort

#Patients (% of 280)

Prestige LP™ PAS Cohort

271 (96.8)

2774

3 (1.1)

3

39 (13.9)

#Patients (% of 265)

0

17, 18

Total # Events

#Patients (% of 333)

Prestige LP™ Safety Cohort

323 (97.0)

3384

3 (0.9)

3

47 (14.1)

Total (Up to 120 Months) # of Patients

Reporting & Total adverse events

Total # Events

#Patients (% of 280)

Prestige LP™ PAS Cohort

275 (98.2)

3523

3 (1.1)

3

Total # Events

ACDF Control

#Patients (% of 265)

-

-

-

-

-

49 (17.5)

-

-

-

-

-

-

-

-

-

-

-

-

-

-

ohort

#Patients (% of 333)

327 (98.2)

4276

3 (0.9)

3

57 (17.1)

Total # Events

17

Based on 24-month cohort.

18

Some adverse event s may lead to additional surgeries or interventions. Refer to Table 4 for more information.

Medtronic Page 25 of 103

6 (2.1) 6 0 (0.0) 0 6 (1.8) 6 6 (2.1)

7

6 (1.8)

7

0 (0.0) 0 0 (0.0) 0 1 (0.3) 1 2 (0.7)

2

3 (0.9)

3

61 (21.8)

117

49 (18.5)

78

72 (21.6)

141

75 (26.8)

156

89 (26.7)

193

Deep Surgical Site

Cervical

55 (19.6)

100

43 (16.2)

67

63 (18.9)

117

70 (25.0)

138

82 (24.6)

164

2 (0.7) 2 2 (0.8) 2 3 (0.9) 3 2 (0.7)

2

3 (0.9)

3

Superfical Surgical Site

Cervical

3 (1.1) 3 0 (0.0) 0 3 (0.9) 3 4 (1.4)

4

4 (1.2)

4

7 (2.5) 8 4 (1.5) 4 13 (3.9)

14

7 (2.5)

8

13 (3.9)

18

NECK AND/OR ARM
PAIN

186 (66.4)

483

156 (58.9)

342

231 (69.4)

598

195 (69.6)

548

241 (72.4)

678

109 (38.9)

162

88 (33.2)

122

136 (40.8)

205

115 (41.1)

173

144 (43.2)

220

Arm Pain (Non-

Cervical)

65 (23.2)

116

48 (18.1)

66

81 (24.3)

143

75 (26.8)

154

95 (28.5)

191

121 (43.2)

196

101 (38.1)

145

150 (45.0)

240

128 (45.7)

210

158 (47.4)

255

Neck Pain

(Non-Cervical)

8 (2.9) 9 9 (3.4) 9 9 (2.7)

10

9 (3.2)

11

10 (3.0)

12

147 (52.5)

290

144 (54.3)

348

172 (51.7)

346

164 (58.6)

352

191 (57.4)

414

27 (9.6)

28

18 (6.8)

20

34 (10.2)

35

32 (11.4)

36

39 (11.7)

43

4 (1.4) 4 6 (2.3) 7 4 (1.2) 4 5 (1.8)

5

5 (1.5)

5

9 (3.2)

9

13 (4.9)

13

10 (3.0)

10

10 (3.6)

12

12 (3.6)

14

Lower Extremity-

20 (7.1)

25

32 (12.1)

43

23 (6.9)

29

28 (10.0)

34

31 (9.3)

39

62 (22.1)

86

43 (16.2)

69

71 (21.3)

99

70 (25.0)

100

80 (24.0)

114

0 (0.0) 0 0 (0.0) 0 0 (0.0) 0 2 (0.7)

2

2 (0.6)

2

Upper And Lower

Extremity-Motor

2 (0.7) 2 2 (0.8) 2 2 (0.6) 2 2 (0.7)

2

2 (0.6)

2

Upper And Lower

Extremity-Sensory

9 (3.2)

9

11 (4.2)

13

11 (3.3)

11

9 (3.2)

9

12 (3.6)

12

12 (4.3)

12

14 (5.3)

14

15 (4.5)

16

14 (5.0)

14

17 (5.1)

18

Upper Extremity-

Sensory

79 (28.2)

115

95 (35.8)

167

94 (28.2)

140

88 (31.4)

138

104 (31.2)

165

2 (0.7)

3

35 (13.2)

38

2 (0.6) 3 6 (2.1)

7

6 (1.8)

7

142 (50.7)

367

123 (46.4)

275

174 (52.3)

440

160 (57.1)

510

195 (58.6)

604

181 (64.6)

486

167 (63.0)

418

221 (66.4)

596

196 (70.0)

609

237 (71.2)

742

61 (21.8)

73

54 (20.4)

62

75 (22.5)

91

73 (26.1)

88

89 (26.7)

108

Malpositioning

Other

INFECTION

(Below Fasciae)-

Other Infection

Other Wound

(Skin To Fasciae)-

Systemic Infection

Urinary Tract Infection

Arm Pain (Cervical)

Neck Pain (Cervical)

NEUROLOGICAL

Carpal Tunnel Syndrome

Gait Disturbance

Lower Extremity-Motor

Sensory

Non-Specific Or Other

Spinal Cord Disturbance

Upper Extremity-Motor

NON-UNION

OTHER

OTHER PAIN

Back Pain

0 0 0 0 0 0 1 0 1 0 0 0 0 0 0

0 0 0 0 0 0 0 0 1 0 0 0 0 0 0

18 10 23 6 6 13 23 4 23 9 10 14 9 11 9

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

13 10 17 5 4 10 20 4 20 9 10 13 7 9 7

2 0 2 0 0 0 0 0 0 0 0 0 0 1 0

0 0 0 1 0 1 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 2 0 2 0 0 0 1 0 1

3 0 4 0 2 2 1 0 1 0 0 1 1 1 1
39 28 46 25 36 34 37 23 42 29 5 31 14 24 20

18 7 20 8 8 14 10 6 10 8 2 9 6 15 11

10 8 13 9 14 11 12 12 15 11 1 11 3 2 4

11 11 13 7 11 8 12 5 14 10 2 11 5 7 5

0 2 0 1 3 1 3 0 3 0 0 0 0 0 0

25 42 30 15 28 19 20 30 22 23 11 26 8 18 11

4 2 4 1 2 1 1 1 1 2 1 3 0 1 0

0 1 0 0 0 0 0 0 0 0 0 0 0 0 0

2 1 2 1 2 2 0 2 0 0 0 0 0 2 0

2 10 2 1 3 2 3 3 4 0 0 0 1 0 1

8 13 9 6 9 7 10 2 11 10 4 11 1 1 2

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

1 0 1 1 2 1 0 1 0 1 0 2 0 0 0

1 2 1 0 1 0 1 0 1 1 1 1 1 1 2

7 13 11 5 9 6 5 21 5 9 5 9 5 13 6

0 1 0 1 0 1 1 2 1 0 0 0 0 1 0

40 26 45 38 31 48 45 43 54 45 31 53 25 13 32

64 49 80 50 45 66 52 50 65 25 30 29 21 19 31

9 6 11 8 8 9 5 5 7 2 2 3 5 4 6

0 (0.0)

0

4 (1.4)

4

1 (0.4)

1

4 (1.5)

4

0 (0.0)

0

4 (1.2)

4

0 (0.0)

0

4 (1.4)

4

-

-

-

0 (0.0)

-

0

-

-

4 (1.2)

-

4

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Medtronic Page 26 of 103

66 (23.6)

92

54 (20.4)

66

79 (23.7)

108

68 (24.3)

102

83 (24.9)

122

24 (8.6)

26

16 (6.0)

17

27 (8.1)

29

32 (11.4)

39

36 (10.8)

43

139 (49.6)

295

135 (50.9)

273

171 (51.4)

368

156 (55.7)

380

189 (56.8)

469

46 (16.4)

68

32 (12.1)

50

55 (16.5)

81

57 (20.4)

95

69 (20.7)

111

127 (45.4)

341

106 (40.0)

242

161 (48.3)

429

149 (53.2)

447

186 (55.9)

558

Cervical-Non-Study

Surgery

69 (24.6)

133

64 (24.2)

112

88 (26.4)

165

88 (31.4)

179

108 (32.4)

214

43 (15.4)

59

18 (6.8)

25

51 (15.3)

68

54 (19.3)

73

64 (19.2)

84

73 (26.1)

149

55 (20.8)

105

91 (27.3)

196

83 (29.6)

195

106 (31.8)

260

106 (37.9)

143

79 (29.8)

116

125 (37.5)

173

121 (43.2)

178

142 (42.6)

214

51 (18.2)

83

26 (9.8)

41

61 (18.3)

100

58 (20.7)

110

70 (21.0)

130

24 (8.6)

30

8 (3.0) 8 26 (7.8)

32

26 (9.3)

33

29 (8.7)

36

3 (1.1) 3 1 (0.4) 1 4 (1.2) 4 3 (1.1)

3

4 (1.2)

4

21 (7.5)

27

7 (2.6) 7 22 (6.6)

28

23 (8.2)

30

25 (7.5)

32

WOUND (NON­INFECTIOUS)

23 (8.2)

34

18 (6.8)

18

25 (7.5)

36

23 (8.2)

34

25 (7.5)

36

1 (0.4) 1 1 (0.4) 1 1 (0.3) 1 1 (0.4)

1

1 (0.3)

1

5 (1.8) 5 1 (0.4) 1 5 (1.5) 5 5 (1.8)

5

5 (1.5)

5

6 (2.1) 6 4 (1.5) 4 6 (1.8) 6 6 (2.1)

6

6 (1.8)

6

14 (5.0)

22

12 (4.5)

12

16 (4.8)

24

14 (5.0)

22

16 (4.8)

24

Lower Extremity Pain

RESPIRATORY

SPINAL EVENT

Cervical-Study Surgery

TRAUMA

UROGENITAL

VASCULAR

Injury Intra-Operative

Headache

Other

Non-Cervical

Other

Csf Leak

Dehiscence

Hematoma

Other

9 9 9 6 3 6 8 5 9 2 5 2 2 4 2

6 3 6 1 3 1 3 4 4 4 0 4 2 0 2
40 31 54 35 31 50 36 36 45 17 23 20 12 11 21

3 4 6 1 2 3 13 10 14 12 8 14 5 3 5

68 31 76 16 47 26 25 30 37 24 14 34 13 6 16

28 14 29 7 21 13 12 9 13 11 5 11 4 5 6

9 2 9 3 2 4 4 3 6 3 2 3 4 1 4

31 15 38 6 24 9 9 18 18 10 7 20 5 0 6

18 15 21 14 20 21 15 15 18 11 15 14 9 7 11

7 6 11 14 5 16 14 11 14 7 7 11 1 1 2

4 1 4 4 2 5 5 1 5 4 1 4 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

4 1 4 4 2 5 5 1 5 4 1 4 0 0 0

2 2 2 0 0 0 1 1 1 0 1 1 0 1 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 1 0

2 2 2 0 0 0 1 1 1 0 1 1 0 0 0

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

-

Medtronic Page 27 of 103

Prestige LP™ IDE Cohort

(N=280)

ACDF Control

(N=265)

Prestige LP™ Safety Cohort

(N=333)

Dysphagia / Dysphonia

0

0 (0.0)

1

1 (0.4)

0

0 (0.0)

Heterotopic Ossification

2

2 (0.7)

5

4 (1.5)

3

3 (0.9)

Implant Events

14

14 (5.0)

5

5 (1.9)

17

17 (5.1)

Neck and / or Arm Pain

1

1 (0.4)

0

0 (0.0)

1

1 (0.3)

Neurological

12

8 (2.9)

9

6 (2.3)

16

10 (3.0)

Non-Union

11

8 (2.9)

8

8 (3.0)

12

9 (2.7)

Other 1 1 (0.4)

28

28 (10.6)

1

1 (0.3)

Other Pain 0 0 (0.0)

1

1 (0.4)

0

0 (0.0)

Spinal Event

4

4 (1.4)

7

4 (1.5)

4

4 (1.2)

Trauma

20

14 (5.0)

8

5 (1.9)

21

15 (4.5)

Wound (Non-Infectious)

1

1 (0.4)

0

0 (0.0) 1 1 (0.3)

Any Adverse Event

0

0 (0.0) 1 1 (0.4)

0

0 (0.0)

Prestige LP™ PAS Cohort

(N=280)

ACDF Control

(N=265)

Prestige LP™ Safety Cohort

(N=333)

Dysphagia / Dysphonia

0

0 (0.0)

1

1 (0.4)

0

0 (0.0)

Heterotopic Ossification

13

12 (4.3)

5

4 (1.5)

18

17 (5.1)

Implant Events

19

19 (6.8)

10

8 (3.0)

23

23 (6.9)

Infection 1 1 (0.4)

0

0 (0.0)

1

1 (0.3)

Neck and / or Arm Pain

13

9 (3.2)

11

8 (3.0)

17

11 (3.3)

Neurological

11

8 (2.9)

8

8 (3.0)

12

9 (2.7)

Non-Union

1

1 (0.4)

32

30 (11.3)

1

1 (0.3)

Other 0 0 (0.0)

1

1 (0.4)

0

0 (0.0)

Other Pain 4 4 (1.4)

7

4 (1.5)

4

4 (1.2)

Spinal Event

36

20 (7.1)

9

6 (2.3)

37

21 (6.3)

Trauma 1 1 (0.4)

1

1 (0.4)

1

1 (0.3)

Wound (Non-Infectious)

0

0 (0.0)

1

1 (0.4)

0

0 (0.0)

Any Adverse Event

99

49 (17.5)

86

44 (16.6)

114

61 (18.3)

Table 10c: Adverse Events Classified as Device-Related or Device/Surgical Procedure-

Related According to the Clinical Adjudication Committee through Month 24 – Safety

Population

Device Relationship of
Adverse Event
Determined by CAC

Events

N

Patients

N (%)

Events

N

Patients

N (%)

Events

N

Patients

N (%)

Table 10d: Adverse Events Classified as Device-Related or Device/Surgical Procedure­Related According to the Clinical Adjudication Committee through Month 84 – Safety

Population

Device Relationship of
Adverse Event
Determined by CAC

Events

N

Patients

N (%)

Events

N

Patients

N (%)

Events

N

Patients

N (%)

Medtronic Page 28 of 103

Prestige LP™ PAS Cohort

(N=280)

ACDF Control

(N=265)

Prestige LP™ Safety Cohort

(N=333)

Dysphagia / Dysphonia

0

0 (0.0) - - 0 0 (0.0)

Heterotopic Ossification

15

14 (5.0) - -

24

23 (6.9)

Implant Events

23

21 (7.5) - -

27

25 (7.5)

Infection 1 1 (0.4) - -

1

1 (0.3)

Neck and / or Arm Pain

14

10 (3.6) - -

18

12 (3.6)

Neurological

12

9 (3.2) - -

13

10 (3.0)

Non-Union

1

1 (0.4) - -

1

1 (0.3)

Other 0 0 (0.0) - - 0 0 (0.0)

Other Pain 4 4 (1.4) - - 4 4 (1.2)

Spinal Event

43

26 (9.3) - -

46

29 (8.7)

Trauma 1 1 (0.4) - - 1 1 (0.3)

Wound (Non-Infectious)

0

0 (0.0) - - 0 0 (0.0)

Any Adverse Event

114

56 (20.1) - -

135

73 (21.9)

Adverse Event

Definition

Anatomical/Technical Difficulty

region other than the cervical spine

Cancer

A malignancy or malignant tumor/neoplasm

Cardiac Disorders

Any condition of the heart

Death

Termination of life due to any cause

Dysphagia/Dysphonia

• Dysphonia

• Difficulty in speaking

Gastrointestinal

Any conditi o n pe r taining to the stomach or intestines

Heterotopic Ossification

other region of the body

Implant Events

implant displa cement, implan t lo osening, or imp la nt br e a k i ng

Infection

Neck and/or Arm Pain

are such that ce rvical spine etiology cannot be ruled ou t

Table 10e: Adverse Events Classified as Device-Related or Device/Surgical Procedure-

Related According to the Clinical Adjudication Committee through Month 120 – Safety

Population

Device Relationship of
Adverse Event
Determined by CAC

Events

N

Patients

N (%)

Events

N

Patients

N (%)

Events

N

Patients

N (%)

Table 11: Adverse Event Categories

• Cer v ical Study Surgery

• Non-Cervical

• Dysphagia

• Heterotopic Ossification-Cervical

• Heterotopic Ossification-Non-Cervical

• Implant Events-Breakage

• Implant Events-Displacement

• Implant Events-Displace-Subsidence

• Implant Events-Loosening

• Implant Events-Malpositioning

• Implant Events-Other

• Deep Surgical Site (Below Fasciae)

Cervical

• Oth er Wound
Infection- Non-Surgical/Non-Study Site

• Superficial Surgical Site (skin to fascia)

Cervical

• Systemic

• Urinary Tract

• Other Infection

• Anatomical or tech nical difficulty encountered durin g the original im plantatio n of the

Prestige LP™ device or contr ol tr eatment device occurring at the level of t he s t udy surgery

• Anatomical or tech nical difficulty encountered durin g an additiona l s urgery that in v olved a

• Difficulty in swallowing

• Event involving heterotopic ossification at any region of the cervical spine

• Event involving heterotopic ossification at any region of the spine that is not cervical or any

• Breakage of any impl ant or implant com ponent

• Incomplete or partial dislocation of the impl ant

• Event associated with implant subsidence into the vertebral body when the reported term

includes “subsiden ce”

• Wear around the implant and/or loosening of the implant surface

• Poor or inappropria t e pl a cement of the im pl ant

• Event that is implant-rela ted, but does not meet th e def i n ition of malpos itioned imp lant,

• Infection below the fascia at the surgical incision

• Infection occurring in other surgical wound not involving the study

• Infection near the surface of the surgical incision

• Infection pertaining to the whole body

• Infection of any part of the urinary system

• Any infection not listed above

• Neck Pain (Cervical)

Medtronic Page 29 of 103

• Pain involving the neck region, which does not include neurological systems. The symptoms

• Neck Pain (Non-Cervical)

• Pain involving the neck which does not include neck neurological symptoms. Information is

available at the reported event time to reasonably ru le out cervic al spine etiology

Neurological

extremity and may be radiating, continuing, extending, or spreading to an adjacent anatomy

Non-Union

Failure of vertebral bodies to fuse

Other

Event not associated with any other categories (e.g., weight loss, tinnitus, substance abuse,
insomnia)

Other Pain

extremity pain (e.g., earache, fibromyalgia, non-cardiac chest pain , s ore throat, arthritis)

Respiratory

Ailments or symptoms associated with respiration or the respiratory system

Spinal Event

confirmed via radiologic findings

Trauma

Physical injury caused by a physical force or traumatic event (e.g., motor vehicle accident, fall,
etc.)

Urogenital

Any condition, relating to, affecting, treating, or being the organs or functions of excretion and
reproduction

Vascular

• Vascular-Other

• Disorder or condition in which the vascu lar system is affected

Wound (Non-Infectious)

oozing, scar tissue, incisional edemas, scratches to the skin surface)

• Arm Pain (Cervical)

• Arm Pain (Non-Cervical)

• Carpal Tunnel Syndrome

• Gait Disturbance

• Lower Extremity-Motor

• Lower Extremity-Sensory

• Non-Specific or Other

• Spine Cord Disturbance

• Upper Extremity-Motor

• Upper Extremity-Sensory

• Upper & Lower Extremity-Motor

• Upper & Lower Extremity-Sensory

availabl e at the reported event time to r easonably r ule out cervical spine etiology

• Pain involving the arm, which does not include neurological symptoms. These symptoms

are such that a cervical spine etiology cannot be ruled out

• Pain involving the arm which does not include neck neurological symptoms. Information is

• Event that is descri bes a s C ar pal Tunnel S yn drome or CTS

• Neurological condition in which the ga it is affected

• Event that involves a feeling or awareness of condition wit hin the body resulting fro m

stimulation of motor neur ons that ind uce movements, as nerves or m us cles. Such m o ve ments
would affect any part of the lower extremity including the hip, thigh, calf, foot, or toes and
may be muscular in na t ur e

• Event that involves a feeling or awareness of condition within the body resulting from

stimulation of sensory receptors. Such sensation would affect any part of the lower extremity
including t he h ip, thigh, calf , foot, or toes a nd may be radiating, continuing, extending, or
spreading to an adjacent anatomy

• Neurological even t n ot a ssociated with any other neurologic al categories or are neurol ogical

in nature but n ot specific eno u gh to fit into othe r s u bcategories

• Condition in which there is a dis ruption or dis t urbance to the s pi nal cord

• Event that involves stimulation of the motor neurons that induce movements, as nerves or

muscles. Such events would affect any part of the upper extremity including the shoulder,
brachium, elbow, forearm, hand, and fingers and may be muscular in nature

• Event that involves a feeling or awareness of condition within the body resulting from

stimulation of sensory receptors. Such sensation would affect any part of the upper extremity
including t he s h ou lder, brachium, elbow, forearm, hand, and fingers and may be radiating,
continuing, extending, or spreading to an adjacent anatomy

• Event that involves a feeling or awareness of condition within the body resulting from

stimulation of motor neur ons that ind uce movements , as ner v es or muscles. Such events
would affect any part of the upper or lower extremity and may be muscular in nature

• Event that involves a feeling or awareness of condition within the body resulting from

stimulation of sensory receptors. Such sensation would affect any part of the upper or lower

• Back Pain

• Headache

• Lower Extremity Pain

• Other

• Spinal Event-Cervical Study Surgery

• Spinal Event-Cervical Non-Study Surgery

• Spinal Event-Non-Cervical

• Vascular-Injury (intra-operative)

• Wound (Non-Infectious)- CSF Leak

• Wound (Non-Infectious)-Dehiscence

• Wound (Non-Infectious)-Hematoma

• Wound (Non-Infectious)-Other

Medtronic Page 30 of 103

• Pain (including stiffness, strain, tightness) in an area that is not of the cervical spine region,

occurring in th e back (e.g., low back pain, th or acic back pain , back pain)

• Pain occurring in the head (e.g., headache, migraine headache, head pain)

• Pain occurring in the lower extremity and using the term “pain” (e.g., leg pain, knee pain,

calf pain, foot pain)

• Pain occurring in parts of the body that ar e not cl as sif i ed as headache, back pain, or lower

• Event involving cervical spine diagnoses at the study treatment level; usually confirmed via

radiologic findings

• Event involving cervical spine diagno s es at on e or m ore cervical spine level ( s) , exce pt for th e

treated level; usually confirmed via radiographic findings

• Event involving diagnoses at one or more spine levels other than cervical spine; usually

• Injury to a vascular structure that is sustained during the course of the operative procedure;

initial study surgery only

• Compromise or tear of the dura mater resulting in leakage of cerebral spinal fluid, excluding

infection. Fluid is clear and free of microorganisms

• A bursting open or separation of a wound without the presence of microorganisms

• Swelling or mass of bl oo d (usually cl otted) confin ed to an organ, tis s u e , or s pace and cause d

by a break in a blo o d vessel. Wound is not limited to a specific anatomic region and there is
an absence of microorganisms

• Wound condition in which there is an absence of infection or other feature (e.g., wound

Posterior Mean and 95% BCI19 of

ACDF Control

IDE Cohort

ACDF Control

Safety Cohort

IDE Cohort

ACDF Control

IDE - ACDF

Anatomical /
Technical Difficulty

Cancer

3 (1.1%)

2 (0.8%)

5 (1.5%)

1.1 (0.1%, 2.3%)

0.6% (0.0%, 1.6%)

0.4% (-1.1%, 2.2%)

Cardiac Disorders

15 (5.4%)

18 (6.8%)

18 (5.4%)

5.1% (2.6%, 7.9%)

7.0% (4.0%, 10.3%)

-1.9% (-6.3%, 2.5 %)

Death

0 (0.0%)

3 (1.1%)

0 (0.0%)

0.0% (0.0%, 0.0%)

1.0% (0.0%, 2 . 3% )

-1.0% (-2.3%,0.0%)*

Dysphagia /
Dysphonia

Gastrointestinal

33 (11.8%)

39 (14.7%)

42 (12.6%)

12.2% (8.6%, 16.5%)

13.8% (9.4%, 18.1%)

-1.6% (-7.8%, 4.7 %)

Heterotopic
Ossification

Implant Events

15 (5.4%)

5 (1.9%)

20 (6.0%)

5.5% (2.9%, 8.4%)

1.7% (0.4%, 3.3%)

3.7% (0.4%, 7 . 1% ) *

Infection

33 (11.8%)

27 (10.2%)

39 (11.7%)

11.5% (7.7%, 15.5%)

10.4% (6.6%, 14.1%)

1.1% (-4.6%, 6.9%)

Neck and / or Arm
Pain

Neurological

114 (40.7%)

106 (40.0%)

134 (40.2%)

40.4% (34.3%, 46.3%)

40.4% (34.4%, 46.7%)

0.0% (-8.9%, 9.1%)

Non-Union

1 (0.4%)

33 (12.5%)

1 (0.3%)

0.3% (0.0%, 1.0%)

12.6% (8.4%, 16.8%)

-12.2% (-16.4%, -7.8%)*

Other

91 (32.5%)

82 (30.9%)

111 (33.3%)

32.9% (27.3%, 38.7%)

30.4% (24.8%, 36.5%)

2.5% (-5.8%, 11.1%)

Other Pain

142 (50.7%)

129 (48.7%)

170 (51.1%)

50.2% (44.1%, 56.3%)

49.2% (43.0%, 55.7%)

1.0% (-7.8%, 10.2%)

Respiratory

24 (8.6%)

17 (6.4%)

27 (8.1%)

8.4% (5.0%, 11.7%)

6.4% (3.6%, 9.6%)

2.0% (-2.6%, 6.9%)

Spinal Event

93 (33.2%)

58 (21.9%)

119 (35.7%)

34.8% (28.9%, 40.5%)

20.4% (15.5%, 25.4%)

14.5% (6.5%, 22.9%)*

Trauma

65 (23.2%)

35 (13.2%)

75 (22.5%)

22.8% (17.6%, 27.9%)

13.4% (9.3%, 17.7%)

9.3% (2.3%, 1 6 .2%)*

Urogenital

26 (9.3%)

9 (3.4%)

32 (9.6%)

8.7% (5.2%, 12.2%)

3.5% (1.5%, 5.9%)

5.2% (1.0%, 9 . 7% ) *

Vascular

12 (4.3%)

3 (1.1%)

13 (3.9%)

4.5% (2.2%, 7.1%)

1.0% (0.1%, 2.1%)

3.5% (0.8%, 6 . 4% ) *

Wound (Non­Infectious)

Any adverse Event

257 (91.8%)

219 (82.6%)

307 (92.2%)

92.2% (89.0%, 95.2%)

82.1% (77.0%, 86.7%)

10.2% (4.3%, 16.4%)*

Bayesian analyses were conducted on all adverse events using non-informative priors. The
results are presented in Tables 12a and 12b with 95% Bayesian Credible Intervals (BCI) for the
difference in adverse event rates (Prestige LP™ IDE/PAS – ACDF). BCIs that exclude zero
indicate statistical differences in the adverse event rates between the Prestige LP™ IDE/PAS
cohort and the ACDF Control group while the BCIs that include zero fail to conclude that this is
a statistical difference in the adverse event rates between the two groups. At 24 months based on
the BCIs, statistical differences were noted between groups for the adverse event rates in the
following categories: death, implant events, neck and arm pain, non-union, spinal events, trauma,
urogenital and vascular. All are statistically higher for the Prestige LP™ IDE Cohort except for
death and non-union which was statistically higher for the control group. At 84 months based on
the BCIs, statistical differences were noted between groups for the adverse event rates in the
following categories: implant events, neurological, non-union, urogenital and vascular. All are
statistically higher for the Prestige LP™ IDE Cohort except for non-union which was statistically
higher for the control group.

Table 12a: Bayesian Comparison of Posterior Probabilities of Ad vers e E ven ts at 24 months

Adverse Event

*Asterisk deno te s s ta t is t i cal difference.

Patients Experiencing Adverse Events (%)

2 (0.7%) 0 (0.0%) 2 (0.6%) 0.5% (0.0%, 1.4%) 0.0% (0.0%, 0.1%) 0.5% (0.0%, 1.5%)

26 (9.3%) 22 (8.3%) 29 (8.7%) 9.3% (5.9%, 13.0%) 8.2% (5.0%, 11.7%) 1.1% (-4.0%, 6.3%)

20 (7.1%) 17 (6.4%) 24 (7.2%) 7.7% (4.5%, 11.0%) 5.4% (2.8%, 8.3%) 2.3% (-2.0%, 6.8%)

158 (56.4%) 125 (47.2%) 197 ( 59.2%) 56.3% (50.4%, 62.5%) 47.2% (41.0%, 53.6%) 9.2% (-0.3%, 18.7%)*

21 (7.5%) 13 (4.9%) 22 (6.6%) 8.2% (4.9%, 11.7%) 3.9% (1.8%, 6.3%) 4.2% (-0.1%, 8.5%)

Posterior Mean and 95% HPD of Adverse Event

Rate

Difference of Adverse Event Rate

between LP IDE Cohort and

19

BCI = Bayesian HPD (Highest Posterior Density) Credible Interval

Medtronic Page 31 of 103

Posterior Mean and 95% BCI20

and ACDF Control

ACDF

Control

Anatomical /
Technical Difficulty

0.6% (0.0%, 1 . 6% )

Cancer

6 (2.1%)

5 (1.9%)

9 (2.7%)

2.3% (0.7% , 4 . 2% )

1.4% (0.3%, 2 . 9% )

0.8% (-1.5%, 3.3%)

Cardiac Disorders

39 (13.9%)

37 (14.0%)

47 (14.1%)

12.7% (8.8%, 16.8%)

14.9% (10.7%, 19.7%)

-2.2% (-8.4%, 4.0 %)

Death

2 (0.7%)

5 (1.9%)

3 (0.9%)

0.6% (0.0%, 1 . 5% )

1.9% (0.5%, 3 . 7% )

-1.3% (-3.5%, 0.5%)

Dysphagia /
Dysphonia

Gastrointestinal

64 (22.9%)

64 (24.2%)

80 (24.0%)

22.8% (17.8%, 28.2%)

24.2% (18.8%, 29.6%)

-1.4% (-8.9%, 6.7 %)

Heterotopic
Ossification

Implant Events

20 (7.1%)

9 (3.4%)

27 (8.1%)

7.4% (4.1%, 1 0 .6%)

3.1% (1.1%, 5 . 1% )

4.4% (0.3%, 8 . 4% ) *

Infection

61 (21.8%)

49 (18.5%)

72 (21.6%)

21.9% (17.0%, 27.1%)

18.2% (13.4%, 23.2%)

3.7% (-3.4%, 11.3%)

Neck and / or Arm
Pain

Neurological

147 (52.5%)

172 (51.7%)

52.7% (46.3%, 58.7%)

54.2% (47.7%, 60.1%)

-1.5% (-10.6%, 7.9%)*

Non-Union

2 (0.7%)

35 (13.2%)

2 (0.6%)

0.7% (0.0%, 1 . 7% )

13.3% (9.2%, 17.9%)

-12.6% (-17.4%, -8.3%)*

Other

142 (50.7%)

123 (46.4%)

174 (52.3%)

49.8% (43.8%, 55.9%)

47.4% (41.0%, 53.6%)

2.4% (-6.5%, 11.5%)

Other Pain

181 (64.6%)

167 (63.0%)

221 (66.4%)

63.7% (57.7%, 69.3%)

64.2% (58.1%, 70.2%)

-0.5% (-9.3%, 8.2 %)

Respiratory

46 (16.4%)

32 (12.1%)

55 (16.5%)

15.6% (11.3%, 20.1%)

12.6% (8.5%, 16.7%)

3.0% (-3.3%, 9.4%)

Spinal Event

127 (45.4%)

106 (40.0%)

161 (48.3%)

46.3% (40.3%, 52.5%)

39.0% (33.1%, 45.3%)

7.3% (-1.4%, 16.6%)

Trauma

106 (37.9%)

79 (29.8%)

125 (37.5%)

37.1% (31.1%, 43.0%)

30.5% (25.0%, 36.6%)

6.6% (-2.1%, 15.1%)

Urogenital

51 (18.2%)

26 (9.8%)

61 (18.3%)

17.3% (12.7%, 21.9%)

10.2% (6.5%, 14.1%)

7.0% (1.0%, 1 3 .5%)*

Vascular

24 (8.6%)

8 (3.0%)

26 (7.8%)

8.4% (5.1%, 1 1 .9%)

3.0% (1.1%, 5 . 2% )

5.4% (1.5%, 9 . 8% ) *

Wound (Non­Infectious)

Any adverse Event

271 (96.8%)

232 (87.5%)

323 (97.0%)

96.8% (94.7%, 98.7%)

87.7% (83.4%, 91.9%)

9.0% (4.2%, 1 3 .9%)*

Table 12b: Bayesian Comparison of Posterior Probabilities of A dv erse E ven ts at 84 months

Adverse Event

Patients Experiencing Adverse Events (%) Posterior Mean and 95% HPD of Adverse Eve nt Rate

PAS Cohort

3 (1.1%) 0 (0.0%) 3 (0.9%)

31 (11.1%) 26 (9.8%) 36 (10.8%) 10.9% (7.2%, 14.9%) 9.9% (6.3%, 13.7%) 1.0% (-4.6%, 6.7%)

44 (15.7%) 34 (12.8%) 56 ( 16.8%) 16.3% (11.8%, 20.9%) 12.2% (8.1%, 16.3%) 4.1% (-2.3%, 10.3%)

186 (66.4%) 156 (58.9%) 231 (69.4%) 65.7% (59.9%, 71.2%) 59.6% (53.2%, 65.7%) 6.1% (-2.5%, 15.0%)

23 (8.2%) 18 (6.8%) 25 (7.5%) 8.9% (5. 7% , 12 . 6 % ) 5.7% ( 3.0%, 8.6%) 3.3% (-1.4%, 7.8%)

Safety Cohort PAS Cohort ACDF Control PAS - ACDF

0.0% (0.0%, 0 . 1% ) 0.6% (0.0% , 1.7%)

of Difference of Adverse Event
Rate between LP PAS Cohort

*Asterisk deno te s s ta t is t i cal difference.

Tables 13a and 13b summarize the secondary interventions in the Prestige LP™ device and
control treatment groups that occurred at or before the 24- and 84-month post-operative interval,
respectively. Revisions, removals, and supplemental fixations were considered second surgery
failures in the clinical study. Reoperations were not considered second surgery failures in the
study. Tables 13a and 13b also presents the Bayesian statistical comparison of secondary
surgeries between the Prestige LP™ IDE device and control treatment groups.

Up to 24 months, there were a greater number of subjects undergoing secondary surgical
procedures at the index level in the ACDF control group [19 (7.2 %)] compared to the Prestige
LP™ IDE [14 (5.0%)] and Safety Cohorts [15 (4.5%)]. Bayesian statistical comparison of
secondary surgeries between the Prestige LP™ IDE Cohort and ACDF control treatment groups
were performed (if zero is excluded from the 95% BCI of the difference of the event rates, the
event rates are considered to be statistically different between the two groups).

Up to 84 months, 18 investigational subjects and 29 control subjects had secondary surgical
procedures at the index level. The cumulative rate of secondary surgeries at the index level was

6.6% in the investigational group and 13.6% in the control group. After adjusting for the
propensity score, there was no statistical difference between the two groups in the cumulative
rate of secondary surgeries at the index level. Based on the clinical study data at 7 years, Prestige

20

BCI = Bayesian HPD Credible Interval

Medtronic Page 32 of 103

LP™ patients are trending to be less likely to get a secondary surgery as compared to the ACDF
patents, but not statistically.

Medtronic Page 33 of 103

Postoperative

Posterior Mean and

IDE
Safety Cohort

IDE
Control

Safety Cohort

IDE
Control

Safety Cohort

IDE
Control

Safety Cohort

IDE
Control

Safety Cohort

IDE
Control

Safety Cohort

IDE
Control

Safety Cohort

(% of 280)

Events

Control

(% of 265)

Control

Events
(% of 333

Safety Cohort

Total # Events

–

Revisions22

Removals23

Supplemental
Fixations24

Reoperations

25

Total

0 0 0 1 1 1 2 1 2 1 4 1 4 2 4 5 10 6 3 3 3

14 (5.0)

16

19 (7.2)

21

15 (4.5)

17

5.3% (2.6%, 8.0%)

6.4% (3.5%, 9.5%)

-1.1% (-5.5%, 3.1%)

External bone

stimulator26

Table 13a. Secondary Interventions and Surgical Procedures Up to the 24-Month Visit

95% BCI21 of

Difference of

Secondary Surgery

Cohort

and ACDF Control

restige LP™ IDE

ACDF Control

Complication

growth

Surgery

6 Wks 3 Mos 6 Mos 12 Mos 24 Mos

Control

IDE # Pati ents

0 0 0 0 1 0 1 0 1 0 3 0 0 0 0 0 0 0 0 0 0 1 (0.4) 1 4 (1.5) 4 1 (0.3) 1 0.4% (0.0%, 1.1%) 1.2% (0.1%, 2.6%) -0.8% (-2.5%, 0.7%)

0 0 0 1 0 1 1 0 1 1 1 1 3 2 3 3 7 4 1 2 1

0 0 0 0 0 0 0 0 0 0 0 0 1 0 1 1 2 1 0 1 0 2 (0.7) 2 3 (1.1) 3 2 (0.6) 2 0.5% (0.0%, 1.2%) 1.1% (0.1%, 2.4%) -0.6% (-2.3%, -0.7%)

0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1 1 1 2 0 2 3 (1.1) 3 2 (0.8) 2 3 (0.9) 3 1.1% (0.1%, 2.3%) 0.6% (0.0%, 1.6%) 0.4% (-1.2%, 2.1%)

0 0 0 0 3 3 0 6 (2.3) 6 2.2% (0.5%,4.1%) -2.2% (-4.1%, -0.5%)

10

(3.6)

Total 24 Month

# of Patients Reporting &

Total adverse events

Total #

)

# Patients

# Patients

IDE Total #

10 12 (4.5) 12 11 (3.3) 11 3.7% (1.6%, 6.0%) 4.2% (1.9%, 6.8%) -0.5% (-4.2%, 2.9%)

Posterior Mean and

95% HPD of Secondary

Surgery Rate

Prestige LP™

IDE Cohort

ACDF

Control

21

BCI = Bayesian HPD Credible Interval

22

A procedure that adjusts or in any way modifies the original implant configuration (e.g., adjusting position of the original configuration, removal with replacement with the same

type of study implant).

23

A procedure that removes one or more components of the original implant configuration without replacement with the same type of trial implant. Removals include elective

removals.

24

A procedure at the involved level in which additional spinal devices not approved as part of the protocol are placed. The supplemental fixations do not include external bone

stimulators.

25

A procedure that involves any surgical procedure at the involved level that does not remove, modify, or add any components and that is not considered a Removal. Revision, or

Supplemental Fixation.

26

There were a total of six (6) external bone growth stimulators used in the ACDF Control group upto 24 months. Three (3) occurred at six (6) months, and three (3) occurred at 12

months. No external bone growth stimulators were used in the PAS or Safety Cohorts. Please note that since this additional device was used, these patients were considered
failures in the Primary Endpoint.

Medtronic Page 34 of 103

Posterio r Mean and 95%

Secondary Surg ery Rat e

between LP

PAS
Safety Cohort

PAS
Control

Safety Cohort

PAS
Control

Safety Cohort

PAS
Control

Safety Cohort

PAS
Control

Safety Cohort

(% of 280)

PAS Total # Events

Control Total # Event
Safety Cohort

(% of 333)

Prestige LP™

Prestige™ LP

ACDF Control

(% of 280)

Total # Events

(% of 265)

Control Total # Events

Safety Cohort

(% of 333)

Revisions28

1

(0.4)

5

(1.9)

1

(0.3)

0.4%

(0.0%, 1.1%)

1.6%

(0.2%, 3.2%)

-1.2%

(-3.1%, 0.5%)

1

(0.3)

Removals29

14

(5.0)

21

(7.9)

15

(4.5)

5.0%

(2.5%, 7.7%)

7.7%

(4.4%, 11.0%)

-2.7%

(-7.2%, 1.7%)

19

(5.7)

Supplemental

Reoperations31
Total

18

(6.4)

29

(10.9)

19

(5.7)

6.6%

(3.7%, 9.6%)

10.4%

(6.6%, 14.2%)

-3.7%

(-8.8%, 1.3%)

28

(8.4)

External bone

Table 13b. Secondary Interventions and Surgical Procedures Up to the 84-Month and 120-Month Visits

36 Mos 48 Mos 60 Mos 72 Mos 84 Mos

Complication

Fixations30

growth
stimulator

32

Control

0 1 0 0 0 0 0 0 0 0 0 0 0 0 0

1 1 1 1 2 1 1 4 1 0 1 0 1 1 1

0 2 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 2 0

1 4 1 1 2 1 1 4 1 0 1 0 1 3 1

0 1 0 0 0

# of Patients Reporting &

PAS # Patients

1

14

2

2

(0.7)

3

3

(1.1)

20

Total 84 Month

Total adverse events

(% of 265)

Control # Patients

5

21

5

5

(1.9)

4

(1.5)

7

(2.6)

(0.6)

4

(0.9)

35

7

# Patients

2

3

Posterio r Mean and

95% HPD of Secondary

Surgery Rate

Safety Cohort

Total # Events

1

15

0.5%

2

(0.0%, 1.2%)

1.1%

3

(0.1%, 2.3%)

21

PAS Cohort

ACDF

Control

1.9%

(0.5%, 3.7%)

1.1%

(0.1%,2.4%)

2.7%

(0.8%, 4.7%)

BCI27 of Difference of

PAS Cohort

and ACDF Control

PAS –

-1.4%

(-3.4%, 0.3%)

0.0%

(-1.8%, 1.9%)

-2.7

(-4.7%, 0.8%)

Total 120 Month

# of Patients Reporting &

Total adverse events

PAS # Patients

1 (0.4) 1 - -

18 (6.4) 18 - -

5 (1.8) 5 - -

5 (1.8) 5 - -

27 (9.6) 29 - -

# Patients

Control # Patients

PAS

5

(1.5)

5

(1.5)

Safety Cohort

1

19

5

5

30

27

BCI = Bayesian HPD Credible Interval

28

A procedure that adjusts or in any way modifies the original implant configuration (e.g., adjusting position of the original configuration, removal with replacement with the same

type of study implant).

29

A procedure that removes one or more components of the original implant configuration without replacement with the same type of trial implant. Removals include elective

removals.

30

A procedure at the involved level in which additional spinal devices not approved as part of the protocol are placed. The supplemental fixations do not include external bone

stimulators.

31

A procedure that involves any surgical procedure at the involved level that does not remove, modify, or add any components and that is not considered a Removal. Revision, or

Supplemental Fixation.

32

There was only one external bone stimulator used in ACDF control group from 36 months to 84 month, occurred at 48 months. There were total of 7 external bon stimulator used

in ACDF control group out 84 months. No external bone growth stimulators were used in the PAS or Safety Cohorts. Please note that since this additional device w as used, these
patients were considered failures in the Primary Endpoint.

Total # Events

Medtronic Page 35 of 103

Secondary Surgical

Intervention Category

Time to Index
Level Surg ery

Safety Cohort

C4-C5 displace d device with

scan was positive for osteopenia

C4-C5 explant of Prestige LP™

cervical fusion

Removal

01 Day- <4 Weeks

Safety Cohort

C4-C5 Prestige LP™ artificial disc

secondary to a fall

C4-C5 explant of Prestige LP™

Removal

06 Weeks

Safety Cohort

C5-C6 device extrusion

C5-C6 explant of Prestige LP™

size

Revision

06 Weeks

Safety Cohort

C6-C7 large recurrent disc herniation

stenosis

C6-C7 explant of Prestige LP™

discectomy and fusion

Removal

03 Months

Safety Cohort

Severe neck pain

C5-C6 explant of Prestige LP™

cervical fusion

Removal

06 Months

Safety Cohort

C6-C7 cervical radiculopathy with

C6-C7 explant Prestige LP™ artificial

discectomy and fusion

Removal

06 Months

Safety Cohort

C5-C6 artificia l disc dislodging

C5-C6 explant of Prestige LP™

cervical fusion

Removal

06 Months

Safety Cohort

C3-C4 foraminal stenosis; possible

disc protrusio n

C3-C4 posterior cervical fusion

Supplementa l Fixation

06 Months

Safety Cohort

C5-C6 herniated disc with right

C6-C7 explant Prestige LP™ artificial

discectomy and fusion

Removal

12 Months

Safety Cohort

Radiating paracer vi cal pai n an d rig ht

C4-C5 explant of Prestige LP™

cervical fusion

Removal

12 Months

Safety Cohort

IDE

Neck pain radiating to shoulders

C6-C7 explant of Prestige LP™

artificial disc; anterior ce r v ical fusion

Removal

12 Months
(518 days)

Safety Cohort

IDE

C3-C4, C5-C6 foraminal stenosis

C3-C4, C5-C6 left posterior

laminectomy

Reoperation

12 Months
(528 days)

Safety Cohort

C7 subsidence into the vertebral

traumati c event

C6-C7 explant of Prestige LP™

and fusion

Removal

12 Months

Safety Cohort

C6-C7 cervical radiculopathy with

above.

C5-C7 posterior cervical fusion; C6-C7

Supplementa l Fixation

12 Months

Safety Cohort

C4-C5, C5-C6 left-sided neural

fall

C4-C5, C5-C6 left posteri or

Reoperation

24 Months

Safety Cohort

PAS

Fall; Neural foraminal narrowing at

C4-C5 & C5-C6

Left posterior C5-C6 foraminotomy

Reoperation

24 Months
(708 days)

Safety Cohort

C6-C7 disc herniation; C5-C6

C5-C6 explant of Prestige LP™

discectomy and fusion

Removal

24 Months

Safety Cohort

IDE

C5-C6 radiculopathy

C5-C6 left foraminotomy

Reoperation

24 Months
(743 days)

Safety Cohort

Lifting injury; C5-C6 changes (not

neck pain

C5-C6 explant of Prestige LP™

Removal

36 Months

Safety Cohort

Subsidence into C6, C4-C5 facet

C6-C7 herniated nucleus pulposus

C5-C6 explant of Prestige LP™

Removal

48 Months

Table 14: Secondary Surgical Interventions at the Index Level– Procedure Details

Group Cause/Adverse Even t Action

IDE

IDE

IDE

IDE

IDE

IDE

IDE

IDE

IDE

IDE

fractured vertebrae; subject's bone

compresse d into the verte br al body

and rotated within the disc space

with cord compression and severe

cervical stenosis

posteriorly

C4 impingement; C4-C5 foraminal

upper extremity radiculopathy

shoulder pain

artificial disc followed by anterior

artificial disc followed by anterior

cervical fusion

artificial disc and replacement with new

Prestige LP™ artificial disc; different

artificial disc with an teri or cervical

artificial disc followed by anterior

disc, C5-C7 anterior cervical

artificial disc followed by anterior

disc, C5-C7 anterior cervical

artificial disc, followed by anterior

(01 day)

(49 days)

(56 days)

(150 days)

(159 days)

(215 days)

(259 days)

(262 days)

(423 days)

(469 days)

Continued Access

IDE

IDE

IDE

PAS

PAS

body and lucency as a result of

cervical stenosis. Additionally, the

patient had re moval due to t he s am e

diagnosis at 215 days as referenced

foraminal na r r owing as a result of a

osteophyte

specified, pre-existing) bilateral

upper extremity radiculopathy; axial

arthropathy, C4-C6 osteophytic

spurring an d s tenosis,

artificial disc, anterior microdiscectomy

posterior ce rvical foram inotomy

foraminotomy

artificial disc; C5-C7 partial

vertebrectomy and an terior cervical

artificial disc with fusion, C6-C7

artificial disc replacement

artificial disc; C4-C7 anter ior cervical

discectomy and fusion

(546 days)

(568 days)

(708 days)

(732 days)

(1161 days)

(1394 days)

Medtronic Page 36 of 103

Safety Cohort

C5-C6 Severe cervica lg ia an d

C5-C6 explant of Prestige LP™

fusion

Removal

Reported during

(1518 days)

Safety Cohort

C4-C6 foraminal stenosis

C6-C7 explant Prestige LP™ artificial

discectomy and fusion

Removal

60 Months

Safety Cohort

Study device fusing to bone above it

C5-C6 explant of Prestige LP™

Removal

Reported during

(1897 days)

Safety Cohort

Shortened m us cle syndrom e

C6-C7 explant of Prestige LP™

fusion

Removal

84 Months

Safety Cohort

C4-C7 Cervical spondylosi s, and

osteophytic spu rr ing

C4-C7 Posterolateral fusion with

Supplementa l Fixation

Reported during

months (2499 days)

Safety Cohort

Cervical stenosis, instability, and

C3-C6 Posterior fusion with a llograft,

facetectomy and foraminotomy

Supplementa l Fixation

Reported during

months (2602 days)

Safety Cohort

Cervical Radiculo pathy

C4-C7 Posterior cervical fusion with

Supplementa l Fixation

Reported during

(2645 days)

Safety Cohort

C6-C7 cervical spondylosi s ,

C6-C7 explant of Prestige LP™

decompression

Removal

96 Months

Safety Cohort

Severe Dysphagia; very large

symptoms

Partial C4 an d C5 corpectom y to

Reoperation

96 Months

Safety Cohort

PAS

C5-C6 Foraminal stenosis; right

cervical radiculopathy

C5-C6 Foraminotomy

Reoperation

108 Months
(3128 days)

Safety Cohort

PAS

Removal of Prestige disc

C5-C6 explant of Prestige LP™

artificial disc

Removal

108 Months
(3158 days)

Control

C5-C6 residual foram inal stenosis;

hematoma

C5-C6 left foraminotomy and

hematoma removal

Revision

01 Day- <4 Weeks

(02 days)

Control

C5 small piece of disc material or

weakness

C5-C6 posterior micr o-foraminotomy

Reoperation

06 Weeks

Control

Esophageal perfor at io n/fistula,

C5-C6 removal of the cerv ic al p lat e a nd

esophageal fistula

Removal

03 Months

Control

C5-C6 herniated nucleus pulposus

C5-C7

anterior cervical discectomy and fusion

Revision

03 Months

(88 days)

Control

C7 distribution pain and nu mbness

C5-C7 fusion

Revision

03 Months

(98 days)

Control

C6-C7 disc herniation

C5-C6 Removal of cervical plate,

anterior cervical dis ce ct omy and fusion

Revision

03 Months

Control

C5-C6 Delayed nonunion

C5-C6 bone growth stimulator

Supplementa l Fixation-

Stimulator

06 Months

Control

C5-C6 nonunion

C5-C6 bone growth stimulator

Supplementa l Fixation-

Stimulator

06 Months

Control

C6-C7 pseudarthrosis

C6-C7 bone growth stimulator

Supplementa l Fixation-

Stimulator

06 Months

PAS

PAS

PAS

IDE

PAS

PAS

PAS

PAS

segmental cervical instability and

C6-C7 degenerati ve dis c dis ease

resulting in s houlder and ar m pain

aggravated by altercation at work

bilateral fora minal stenosis an d C 5-

C7 disc bulging and bony

myelopathy

foraminal stenosis, and spurring; C5-

C6 osteophyte complex, stenosis;

C7-T1 bulge

artificial disc, hemi corpectomy, and

strut fusion with instrumentation; C6-

C7 anterior cervical discectomy and

disc, C4-C6 anterior cervical

artificial disc

artificial disc, C5-C6 anterior

decompression; C5-C7 an terior cervical

instrumenta ti o n, la minectomies ,

autograft, and allograft

autograft, and bon e mor phogenic
protein and C3-C5 laminectom y,

instrumentation and C5-C6

foraminotomy and facetectomy

artificial disc; C6-C7 anterior cer vi ca l

discectomy and fusion with

ATLANTIS™ plate, al lo gr aft,

demineralized bone extender;

corpectomy, and foraminal

PAS but Occurred

before or at 84

months

(1646 days)

PAS but Occurred

before or at 84

months

(2431 days)

PAS but Occurred

before or at 84

PAS but Occurred

before or at 84

PAS but Occurred

before or at 84

months

(2907 days)

PAS

osteophyte at C4-C5; worsen ing of

hematoma per MRI, deltoid

abscess

decompress the esophagus

(C5)

allograft; explo ration and debridement

of an esophageal abscess , repair of an

explorati on of fusion at C5 -C6; C6-C7

External Bone Growth

External Bone Growth

External Bone Growth

(3038 days)

(43 days)

(63 days)

(140 days)

(183 days)

(185 days)

(207 days)

Medtronic Page 37 of 103

Control

C5-C6 nonunion, failed fusion with

C5-C6 removal of the cerv ic al p lat e a nd

anterior cervical fusion

Removal

06 Months

Control

Posterior cervical region and

arm pain

C5-C6 removal of the cerv ic al p lat e a nd

bilateral foraminotomies

Removal

06 Months

Control

C5-C6, C6-C7

C5-C7 bone growth stimulator

Supplementa l Fixation-

Stimulator

12 Months

Control

C5-C6 nonunion

C5-C6 removal of the cerv ic al p lat e a nd

microdissection, and fusion

Removal

12 Months

Control

C5-C6 pseudarthrosis

C5-C6 removal of the cerv ic al p lat e a nd

allograft; allograft and plate replaced

Removal

12 Months
(293 days)

Control

C5-C6, C6-C7 nonunion; wound

infection

C5-C7 removal of the cerv ic al p lat e a nd

allograft; revision anterior arthrodesis

Removal

12 Months
(326 days)

Control

C5-C6 pseudarthrosis

C5-C6 external bone growt h s timulator

Supplementa l Fixation-

Stimulator

12 Months

Control

C6-C7 nonunion

C6-C7 bone growth stimulator

Supplementa l Fixation-

Stimulator

12 Months

Control

C5-C6 possible facet dis ease; neck

pain

C6-C7 removal of the cerv ic al p lat e t o

discectomy and fusion

Elective Removal

12 Months

Control

C6-C7 non-union with motion

C6-C7 removal of the cerv ic al p lat e a nd

fusion

Removal

12 Months

Control

Shoulder pain and numbness in

C5-C6 removal of the cerv ic al p lat e t o

and fusion

Elective Removal

12 Months

Control

Neck and arm pa in; possible
recurrent nerve compression

C5-C6 posterior cervical fusion

Supplementa l Fixation

12 Months
(474 days)

Control

Involuntary movements thumb; gait

down; urinary incontinence

C4, C5, C6, C7, T1 laminectomies

Reoperation

12 Months

Control

Cervical spondylosis, neck pain,

C5-C6 removal of the cerv ic al p lat e t o

discectomy and fusion

Elective Removal

12 Months

Control

C5-C6, C6-C7

nonunion

C5-C7 posterior fusion

Supplementa l Fixation

12 Months
(535 days)

Control

C5-C6 pseudarthrosis

C5-C6 posterolateral cervical fusion

Supplementa l Fixation

24 Months
(613 days)

Control

C5-C6 discogenic pain confirmed via

C6-C7 removal of the cerv ic al p lat e t o

discectomy and fusion

Elective Removal

24 Months

Control

C5-C6 lucency

C5-C6 removal of the cerv ic al p lat e a nd

marrow aspiration (left anterior ilium)

Removal

24 Months

Control

C5-C6, C6-C7 lateral stenos is

C5-C6, C6-C7 right foraminotomies

with C6-C7 nerve root decompression

Revision

36 Months

(1050 days)

Control

C6-C7 delayed fusion; possibly work

related

C6-C7 posterior fusion

Supplementa l Fixation

36 Months

(1094 days)

Control

C6-C7 osteophytes, cord edema,

vehicle accident

C5-C6 removal of the cerv ic al p lat e t o

Elective Removal

36 Months

Control

C6-C7 pseudarthrosis; resorption of

graft

C6-C7 posterior fusion

Supplementa l Fixation

36 Months

(1259 days)

Control

C6-C7 pseudoarthrosis; resorption of

Supplementa l Fixation-C6-C7 bone

Supplemental Fixation-

Stimulator

48 Months

Control

C6-C7 herniation, foramen

C5-C6 removal of the cerv ic al p lat e t o

interbody fusion

Elective Removal

48 Months

motion pres ent

trapezius pain, spasms, and bilateral

nonunion

pain with right posterior scapular

present, ne ck and shoulder pain

fingers

allograft; partial corpectomy C5 with

allograft; anterior cervica l fusion;

allograft; partial corpectomy at C6,

facilitate C5-C6 anterior cervical

allograft; C4-C7 anterior cervical

facilitate C6-C7 cervi cal discectomy

External Bone Growth

External Bone Growth

External Bone Growth

(241 days)

(272 days)

(278 days)

(284 days)

(352 days)

(372 days)

(385 days)

(399 days)

(407 days)

abnormalities; upper and lower

extremity de f icits and findings

suggestiv e of upper motor neuron

lesion; body "jumps" when lays

glenohumeral joint

discogram

herniated n ucleus pulposus, spinal

stenosis, rad i a t i ng neck pain, motor

graft

facilitate C6-C7 anterior cervical

facilitate C5-C6 anterior cervical

allograft; anterior cervica l fusion with

autologous stem cells, and bone

facilitate C6-C7 anterior cervical

discectomy and fusion

growth stim u lator

External Bone Grown

(506 days)

(513 days)

(756 days)

(840 days)

(1211 days)

(1391 days)

Medtronic Page 38 of 103

impingement, osteophyte

compression

facilitate C6-C7 anterior discectomy

and osteophytectomy with anterior

(1512 days)

Control

Neck and left arm pain

C5-C6 removal of the cerv ic al p lat e t o

arthrodesis

Elective Removal

48 Months

Control

C3-C4 severe spondylitic changes

changes

C5-C6 removal of the cerv ic al p lat e t o

Elective Removal

60 Months

Control

C5-C6 herniation, C4-C6 foraminal

C6-C7 removal of the cervical plat e t o

anterior plate

Elective Removal

60 Months

Control

C5-C6 degenerati ve chan g es

osteophytes

C6-C7 removal of the cerv ic al p lat e t o

discectomy and fusion

Elective Removal

60 Months

Control

C3-C4 protrusion, hypertrophy; C5-

segment degenerat io n

C4-C5 removal of the cervical plate to

cervical discectomy and fusion

Elective Removal

60 Months

Control

C6-C7 spondylosis, disc b ulge

C5-C6 removal of the cerv ic al p lat e t o

replacement

Elective Removal

72 Months

Control

C5-C6 osteophytosis and arthropathy

C6-C7 removal of the cerv ic al p lat e t o

discectomy and fusion

Elective Removal

84 Months

Control

C6 right radiculopathy,

C6-C7 foraminal narrowing

C5-C6 right anterolateral for aminotomy

Reoperation

84 Months

(2486 days)

Control

C5-C6 epidural abscess

C5-C6 laminectomy with evacuation of

epidural abscess

Reoperation

84 Months

(2514 days)

Time Point

Variable

Prestige LP™

Success (%)

ACDF Control

Success (%)

Prestige LP™

Success (%)

6 Weeks

Overall

Improved

187 (67.3%)

144 (56.7%)

229 (69.2%)

Stable

65 (23.4%)

78 (30.7%)

74 (22.4%)

with bilateral spurring, lef t

paracentral disc osteo p hy t e c omplex,

bilateral foraminal encroachment,

and C4-C5 severe spondylitic

stenosis

possible small disc protrusion,

C6 mild stenosis, protrusion,

facilitate C6-C7 foraminotomy with

facilitate C3-C5 anterior cervical

discectomy and fusion

facilitate C5-C6 discectomy with

facilitate C5-C6 anterior cervical

facilitate C3-C4, C5-C6 anterior

facilitate C6-C7 art if icial disc

facilitate C5-C6 anterior cervical

(1560 days)

(1665 days)

(1679 days)

(1729 days)

(1806 days)

(2242 days)

(2425 days)

Neurological status was evaluated by assessment of motor function, sensory function, and
reflexes.

Overall neurological status at 6 weeks, 3 months, 6 months, 12 months, 24 months, 36 months,
60 months and 84 months is provided for the Prestige LP™ and Control subjects. Neurological
status at 120 months is provided for Prestige LP™ cohorts only in Table 15 below.

Neurologic success was defined as maintenance or improvement in neurologic status at 24
months and 84 months compared to baseline. The success rates at 24 months postoperative were

93.3%, 94.1% and 83.6% for the Prestige LP™ IDE Cohort, Prestige LP™ Safety Cohort and
Control group, respectively. The success rates at 84 months postoperative were 92.7%, 92.5%
and 79.7% for the Prestige LP™ IDE Cohort, Prestige LP™ Safety Cohort and Control group,
respectively.

As shown in Table 16, at 24 months, the neurological success rate in the Prestige LP™ IDE
Cohort is statistically superior to that of the ACDF Control group with the posterior probability
of superiority being 99.9%. At 84 months, both non-inferiority and superiority of the
investigational treatment to the control treatment was established in neurological maintenance or
improvement with the posterior probability of non-inferiority and superiority both being
essentially 100.0%.

Table 15: Neurological Success

Medtronic Page 39 of 103

IDE/PAS Cohort (N=280)

(N=265)

Safety Cohort (N=333)

Time Point

Variable

Prestige LP™

Success (%)

ACDF Control

Success (%)

Prestige LP™

Success (%)

Deteriorated

26 (9.4%)

32 (12.6%)

28 (8.5%)

3 Months

Overall

Improved

194 (70.3%)

136 (56.4%)

238 (72.3%)

Stable

63 (22.8%)

74 (30.7%)

72 (21.9%)

Deteriorated

19 (6.9%)

31 (12.9%)

19 (5.8%)

6 Months

Overall

Improved

195 (72.2%)

141 (61.8%)

239 (74.0%)

Stable

59 (21.9%)

64 (28.1%)

68 (21.1%)

Deteriorated

16 (5.9%)

23 (10.1%)

16 (5.0%)

12 Months

Overall

Improved

198 (72.8%)

133 (58.8%)

242 (74.5%)

Stable

59 (21.7%)

61 (27.0%)

68 (20.9%)

Deteriorated

15 (5.5%)

32 (14.2%)

15 (4.6%)

24 Months

Overall

Improved

196 (72.6%)

123 (55.9%)

239 (74.2%)

Stable

56 (20.7%)

61 (27.7%)

64 (19.9%)

Deteriorated

18 (6.7%)

36 (16.4%)

19 (5.9%)

36 Months

Overall

Improved

176 (73.9%)

86 (53.4%)

217 (75.1%)

Stable

53 (22.3%)

48 (29.8%)

62 (21.5%)

Deteriorated

9 (3.8%)

27 (16.8%)

10 (3.5%)

60 Months

Overall

Improved

138 (70.4%)

110 (58.2%)

177 (72.2%)

Stable

48 (24.5%)

52 (27.5%)

57 (23.3%)

Deteriorated

10 (5.1%)

27 (14.3%)

11 (4.5%)

84 Months

Overall

Improved

147 (71.0%)

99 (54.4%)

182 (71.9%)

Stable

45 (21.7%)

46 (25.3%)

52 (20.6%)

Deteriorated

15 (7.2%)

37 (20.3%)

19 (7.5%)

120 Months

Overall

Improved

160 (71.4%)

-

197 (73.2%)

Stable

47 (21.0%)

-

54 (20.1%)

Deteriorated

17 (7.6%)

-

18 (6.7%)

IDE/PAS Cohort (N=280)

(N=265)

Safety Cohort (N=333)

Final Effectiveness Findings (Key Endpoints)
Primary Effectiveness Analysis

The effectiveness variables represent those measurements that describe the clinical outcomes of
the study subjects. The primary endpoint is a composite endpoint that takes into account the
success of NDI, Neurological Status, FSU height and the absence of serious implant related
adverse events or secondary surgeries. Additional secondary endpoints include radiographic
success, indicators of pain relief, general health status, and doctor and subject perceptions of
outcomes. Please note that this was a non-randomized study with a historical control.

Study success was expressed as the number of individual subjects categorized as a success
divided by the total number of subjects evaluated. Table 16 describes the observed success rates
and Bayesian analyses for individual outcome parameters and overall success.

At 24 months, the observed success rates are the outcomes of the clinical trial. Posterior means
for each group can be interpreted as the average chance of success at 24 months, and the
posterior mean of the difference can be interpreted as the average difference in the chance of
success at 24 months. When a patient receives the Prestige LP™ device, the average chance of
overall success (without FSU) as defined in the clinical study at 24 months is 78.9%. Given the

Medtronic Page 40 of 103

results of the trial, there is a 95% probability that the chance of success ranges from 74.1% to

84.0%. When a patient receives the control treatment, the average chance of overall success
(without FSU) at 24 months is 67.8%. Given the results of the trial, there is a 95% probability
that the chance of success ranges from 61.2% to 74.0%. The average difference in the change of
success (without FSU) between the IDE cohort and the ACDF control is 11.1% with 95%
probability that this difference will fall in range of 2.7% to 19.6%. Overall success (without
FSU) the posterior probability of non-inferiority of the IDE cohort to the ACDF control group is
essentially 100%, reaching the primary objective.

At 84 months, the observed success rates are the outcomes of the clinical trial. Posterior means
for each group can be interpreted as the average chance of success at 84 months, and the
posterior mean of the difference can be interpreted as the average difference in the chance of
success at 84 months. When a patient receives the Prestige LP™ device, the average chance of
overall success (without FSU) as defined in the clinical study at 84 months is 74.6%. Given the
results of the trial, there is a 95% probability that the chance of success ranges from 68.7% to

80.6%. When a patient receives the control treatment, the average chance of overall success
(without FSU) at 84 months is 63.7%. Given the results of the trial, there is a 95% probability
that the chance of success ranges from 56.3% to 70.9%. The average difference in the change of
success (without FSU) between the PAS cohort and the ACDF control is 10.9% with 95%
probability that this difference will fall in range of 0.8% to 20.5%. Both non-inferiority and
superiority of the investigational treatment over the control treatment group were established for
overall success (without FSU) with the posterior probability of non-inferiority and superiority,
respectively, being essentially 100.0% and 98.5%.

At 120 months, the observed overall success rate (without FSU) was 74.3%.

All success probabilities were for the 24 and 84 months outcomes, and posterior probabilities of
success were calculated using Bayesian statistical methods and are presented in Table 16.

Medtronic Page 41 of 103

24-Month Observed

Success Rate

24-Month Pos t erior Probabilities

(IDE vs Control)

IDE

Cohort

ACDF

Control

IDE Cohort

ACDF Control

IDE Cohort –

ACDF Control

Non-Inferiority

Superiority

237/270
(87.8%)

177/219
(80.8%)

87.2%

(83.1%, 91. 2% )

82.4%

(77.0%, 87.5%)

4.8%

(-2.0%, 11.8%)

Neurological

252/270

184/220

93.4%

83.6%

9.9%

Overall Success
(without FSU)33

215/271
(79.3%)

147/220
(66.8%)

78.9%

(74.1%, 84. 0% )

67.8%

(61.2%, 74. 0% )

11.1%

(2.7%, 19.6%)

Overall Success
(with FSU)34

159/226
(70.4%)

108/171
(63.2%)

68.9%

(62.7, 75.1%)

65.7%

(58.3%, 73. 4% )

3.2%

(-7.0%, 13.4%)

84-Month Observed

Success Rate

84-Month Pos t erior Probabilities

(PAS vs Control)

PAS

Cohort

ACDF

Control

PAS Cohort

ACDF Control

PAS Cohort –

ACDF Control

Non-Inferiority

Superiority

179/208
(86.1%)

145/181
(80.1%)

86.2%

(81.3%, 90.8%)

80.1%

(73.7%, 86.0%)

6.1%

(-1.7%, 14.6%)

Neurological
Status

192/207
(92.8%)

145/182
(79.7%)

92.7%

(88.8%, 96.0%)

80.0%

(73.8%, 86.0%)

12.7%

(5.3%, 19.9%)

134/160
(83.8%)

123/127
(96.9%)

82.8%

(76.4%, 88.8%)

97.3%

(94.5%, 99.5%)

-14.5%

(-21.7%, 7.5%)

Overall Success
(without FSU)35

158/211
(74.9%)

115/182
(63.2%)

74.6%

(68.7%, 80.6%)

63.7%

(56.3%, 70.9%)

10.9%

(0.8%, 20.5%)

Overall Success

103/166

81/135

61.2%

61.2%

0.1%

120-Month Observed

Success Rate

120-Month Posterior

Probabilities (PAS vs Control)

PAS

Cohort

ACDF

Control

PAS Cohort

ACDF Control

PAS Cohort –

ACDF Control

Non-Inferiority

Superiority

197/224

(87.9%)

Status

(92.4%)

124/164

(75.6%)

Overall Success
(with FSU)38

94/176

(53.4%)

Table 16: Observed Success Rates and Posterior Probabilities of Success at 24 Months

Primary

Outcome

Variable

24-Month Posterior Mean (95% HPD Credible Interval)

NDI

Status
FSU

Primary

Outcome

Variable

NDI

FSU

(with FSU)36

Primary

Outcome

Variable

NDI
Neurological

(93.3%)
205/224

(91.5%)

(62.0%)

207/224

~100.0% 91.2%

(83.6%)
156/164

(95.1%)

(60.0%)

- - - - - -

- - - - - -

(90.3%, 96.2%)

91.7%

(87.8%, 95. 2% )

84-Month Posterior Mean (95% HPD Credible Interval)

(53.5%, 68.8%)

120-Month Posterior Mean (95% HPD Credible Interval)

(78.2%, 88. 5% )

95.1%

(91.6%, 98.3%)

(52.6%, 69.9%)

(3.8%, 16.1%)

-3.4%

(-8.5%, 2.1%)

(12.4%, 12. 2% )

~100.0% 99.9%

99.2% 9.7%

~100.0% 99.5%

99.5% 73.6%

~100.0% 92.6%

~100.0% ~100.0%

9.6% 0.000%

~100.0% 98.5%

94.5% 50.6%

FSU
Overall Success

(without FSU)

37

171/230

(74.3%)

- - - - - -

- - - - - -

- - - - - -

At 24 months, statistical superiority of the Prestige LP™ Cervical Disc group was demonstrated
for overall success (when not including FSU data) and the neurological component for the
population studied in the clinical trial postoperatively since the posterior probability of
superiority for both endpoints are over 99.0%, exceeding the threshold of 95.0%. With FSU data

33

A success is a patient who had successes in NDI and neurological status and had no additional surgery classifi ed as ‘failure’

and no serious device o r device/surgery associated ad verse event.

34

A success is a patient who had successes in NDI, neurological status, and FSU and had no additional surgery classified as

‘failure’ and no serious device or device/surgery associated adverse event.

35

A success is a patient who had successes in NDI and neurological status and had no additional surgery classified as ‘failure’

and no serious device o r device/surgery associated ad verse event.

36

A success is a patient who had successes in NDI, neu ro logical status, and FSU and had no additional surgery classified as

‘failure’ and no serious device or device/surgery associated adverse event.

37

A success is a patient who had successes in NDI and neurological status and had no additional surgery classifi ed as ‘failure’

and no serious device o r device/surgery associated ad verse event.

38

A success is a patient who had successes in NDI, neurological status, and FSU and had no additional surgery classified as

‘failure’ and no serious device or device/surgery associated adverse event.

Medtronic Page 42 of 103

included, the average chance of overall success, as defined in the clinical study is 68.9%. These
results are lower than when excluding FSU data. Given the results of the trial, there is a 95%
probability that the chance of success ranges from 62.7% to 75.1%. However, the average chance
of success for the control group (with FSU) is also lower, at 65.7%, with a 95% probability that
the chance of success ranges from 58.3% to 73.4%. The average difference in the chance of
success between the IDE cohort and the ACDF control group is 3.2% with 95% probability that
this difference will fall in range of -7.0% to 13.4%. Thus, while the rates of success were lower
for the investigational device when including FSU data, the success rates were also lower for the
control group, and the probability of non-inferiority for the investigational device was
statistically achieved. Thus, it can be stated that the investigational device is statistically non­inferior to the control procedure as the posterior probability of non-inferiority is 99.5%.

The NDI, FSU, and overall success (with FSU) variables were found to be statistically non­inferior at 24 months postoperatively.

At 84 months, statistical superiority of the Prestige LP™ Cervical Disc group was demonstrated
for overall success (when not including FSU data) and the neurological component for the
population studied in the clinical trial postoperatively since the posterior probability of
superiority for both endpoints are over 98.0%, exceeding the threshold of 95.0%. With FSU data
included, the average chance of overall success, as defined in the clinical study is 61.2%. These
results are lower than when excluding FSU data. Given the results of the trial, there is a 95%
probability that the chance of success ranges from 53.5% to 68.8%. However, the average chance
of success for the control group (with FSU) is also lower, at 61.2%, with a 95% probability that
the chance of success ranges from 52.6% to 69.9%. The average difference in the chance of
success between the PAS cohort and the ACDF control group is 0.1% with 95% probability that
this difference will fall in range of 12.4% to 12.2%. Non-inferiority of the investigational
treatment over the control treatment could not be claimed for overall success (with FSU) at 84
months with the posterior probability of non-inferiority being 94.5%, missing the non-inferiority
criteria by only 0.5%. However, it was established for overall success (with FSU) at 36 and 60
months.

FSU success rate was above 90% for both treatment groups at all follow-ups, except at 84 and
120 months for the investigational group. The FSU success rate in the investigational group was

83.8% at 84 months and 75.6% at 120 months; A success or failure determination of FSU could
not be made for 42.9% of the investigational group at 84 months and 41.4% at 120 months due to
both the lost-to-follow-ups and the visualization challenges inherent even in this measurement.
FSU non-inferiority in the investigational group was missed at the 84 months. However, this is a
numerical finding that doesn’t have a clinically meaningful impact on the overall performance of
the Prestige LP™ device.
At 120 months, as there was no control at this time point no statistical comparisons were made.

The time course of overall success for each treatment group is shown in Table 17.

Medtronic Page 43 of 103

3-Month Observed

Success Rate

6-Month Observed

Success Rate

12-Month Observed

Success Rate

24-Month Observed

Success Rate

IDE

Cohort

ACDF

Control

IDE

Cohort

ACDF

Control

IDE

Cohort

ACDF

Control

IDE

Cohort

ACDF

Control

257/276
(93.1%)

210/241

(87.1%)

254/270
(94.1%)

205/228
(89.9%)

257/272
(94.5%)

194/226
(85.8%)

252/270
(93.3%)

184/220
(83.6%)

Overall Success
(without FSU)

223/277
(80.5%)

154/239

(64.4%)

223/271
(82.3%)

158/224
(70.5%)

226/274
(82.5%)

150/223
(67.3%)

215/271
(79.3 %)

147/220
(66.8%)

36-Month Observed

Success Rate

60-Month Observed

Success Rate

84-Month Observed

Success Rate

120-Month Observed

Success Rate

PAS

Cohort

ACDF

Control

PAS

Cohort

ACDF

Control

PAS

Cohort

ACDF

Control

PAS

Cohort

ACDF

Control

Table 17: Time Course of Observed Success Rates

Primary Out come

Variable

NDI

Neurological Status

FSU

39

Overall Success
(with FSU)

Primary Out come

NDI

Neurological Status

FSU

Overall Success
(without FSU)

Overall Success
(with FSU)

40

Variable

42

41

241/276
(87.3%)

229/235
(97.4%)

187/238
(78.6%)

216/239
(90.4%)

229/238
(96.2%)

178/195
(91.3%)

200/241
(83.0%)

149/200
(74.5%)

174/235
(74.0%)

182/182

(100%)

113/181
(62.4%)

127/159
(79.9%)

134/161
(83.2%)

118/120
(98.3%)

103/160
(64.4%)

81/126

(64.3%)

241/271
(88.9%)

227/230
(98.7%)

188/233
(80.7%)

168/197
(85.3%)

186/196
(94.9%)

147/162
(90.7%)

153/199
(76.9%)

118/167
(70.7%)

173/224
(77.2%)

174/175
(99.4%)

119/174
(68.4%)

156/187
(83.4%)

162/189
(85.7%)

128/134
(95.5%)

133/188
(70.7%)

90/141

(63.8%)

241/272
(88.6%)

225/233
(96.6%)

186/234
(79.5%)

179/208
(86.1%)

192/207
(92.8%)

134/160
(83.8%)

158/211
(74.9%)

103/166
(62.0%)

176/222
(79.3%)

164/172
(95.3%)

110/173
(63.6%)

145/181
(80.1%)

145/182
(79.7%)

123/127
(96.9%)

115/182
(63.2%)

81/135

(60.0%)

237/270
(87.8%)

205/224
(91.5%)

159/226
(70.4 %)

197/224
(87.9%)

207/224
(92.4%)

124/164
(75.6%)

171/230
(74.3%)

94/176

(53.4%)

177/219
(80.8%)

156/164
(95.1%)

108/171

(63.2 %)

-

-

-

-

-

Table 18 provides overall success data for each treatment group stratified by the treated level
including post-hoc statistical analysis and comparisons between the Prestige LP™ IDE/PAS
Cohort and the ACDF Control group through the 24- and 84-month time points using Frequentist
methods. At 24 months, overall success rates (without FSU) were not significantly different
between the Prestige LP™ IDE Cohort and ACDF Control group at any treatment level except
for at the C6-C7 level, in which the IDE cohort had a significantly higher success rate compared
to the control group. Overall success rates (with FSU) at 24 months were not significantly
different between the IDE cohort and control group at any treatment level.

At 84 months, overall success rates (without FSU) were not significantly different between the
Prestige LP™ IDE Cohort and ACDF Control group at any treatment level except for at the C5­C6 level, in which the IDE cohort had a significantly higher success rate compared to the control
group at 84 months. Overall success rates (with FSU) at 84 months were not significantly
different between the IDE cohort and control group at any treatment level.

39

A success is a patient who had successes in NDI and neurological status and had no additional surgery classified as ‘failure’

and no severe device or device/surgery associated adverse event.

40

A success is a patient who had successes in NDI, neu ro logical status, and FSU and had no additional surgery classified as

‘failure’ and no severe device or device/surgery associated adverse event.

41

A success is a patient who had successes in NDI and neurological status and had no additional surgery classified as ‘failure’

and no severe device or device/surgery associated adverse event.

42

A success is a patient who had successes in NDI, neurological status, and FSU and had no additional surgery classified as

‘failure’ and no severe device or device/surgery associated adverse event.

Medtronic Page 44 of 103

IDE 24-Month

PAS 84-Month

(N = 280)

(N = 265)

Point Estimate and 95%

ACDF Control Cohort

(N = 280)

(N = 265)

Point Estimate and 95%

ACDF Control Cohort

Overall Success

C6-C7

Overall Success

C6-C7

IDE 24-Month

PAS 84-Month

Prestige LP™

IDE Cohort

Prestige LP™
Safety Cohort

Prestige LP™

PAS Cohort

Prestige LP™
Safety Cohort

Non-

(N = 9)

Non-

(N = 22)

Non-

(N = 13)

Non-

(N = 9)

Non-

(N = 22)

Non-

(N = 13)

Overall

FSU)

Overall

FSU)

Table 18: Overall Success by Level Treated at 24 Months and 84 Months

(without FSU)

• C3-C4

• C4-C5

• C5-C6

•

(with FSU)

• C3-C4

• C4-C5

• C5-C6

•

46

Prestige LP™

IDE Cohort

45

• 3/4 (75.0% )

• 16/20 (80.0%)

• 106/140 (7 5. 7%)

• 90/107 (84.1%)

• 2/3 (66.7% )

• 12/19 (63.2%)

• 93/133 (69.9%)

• 52/71 (73.2%)

ACDF Control

• 4/8 (50.0% )

• 6/11 (54.5% )

• 84/125 (67.2%)

• 53/76 (69.7%)

• 4/5 (80.0% )

• 5/10 (50.0% )

• 72/115 (62.6%)

• 27/41 (65.9%)

Confidence Interval43 of

Difference of Success Rate

between IDE Cohort an d

• 25. 0% (-34.2 %, 84. 2%)

• 25. 5% (-7.9 %, 58. 9%)

• 8. 5% (-2.4%, 19.4% )

• 14. 4% (2.2%, 26. 5% )

• -13.3% ( -75.3%, 48. 6%)

• 13. 2% (-24.6 %, 50. 9%)

• 7.3% (-4.5%, 19.1%)

• 7.4% (-10.1%, 24.9%)

Prestige LP™

PAS Cohort

• 2/3 (66.7% )

• 9/15 (60.0% )

• 79/104 (76.0%)

• 68/89 (76.4%)

• 2/3 (66.7% )

• 7/14 (50.0% )

• 62/91 (68.1%)

• 32/58 (55.2%)

ACDF Control

• 3/8 (37.5% )

• 6/10 (60.0% )

• 61/105 (58.1%)

• 45/59 (76.3%)

• 3/6 (50.0% )

• 3/7 (42.9% )

• 49/89 (55.1%)

• 26/33 (78.8%)

Confidence Interval44 of

Difference of Success Rate

between PAS Cohort and

• 29.2% (-36.9%, 95.2%)

• 0. 0% (-39.2 %, 39. 2%)

• 17.9% (5.1%, 30.6%)

• 0. 1% (-13.8 %, 14. 1%)

• 16. 7% (-52.2 %, 85. 5%)

• 7. 1% (-38.2 %, 52. 5%)

• 13. 1% (-1.1 %, 27. 3%)

• -23.6% ( -44.2%, 3. 1%)

Overall success data stratified by patient race at the 24- and 84-month time points are also
provided in Table 19. Due to the relatively small numbers of non-Caucasians treated in the IDE,
statistical conclusion for outcomes based on race cannot be reliably made and will be evaluated
further as part of an Enhanced Surveillance Study Medtronic Sofamor Danek will conduct for 10
years postmarket.

Table 19: Overall Success by Patient Race

Overall
Success

Caucasian
(N = 271)

Caucasian

ACDF Control

Caucasian

(N = 243)

Caucasian

Caucasian

(N = 320)

Caucasian

Caucasian
(N = 271)

Caucasian

ACDF Control

Caucasian
(N = 243)

Caucasian

Caucasian

(N = 320)

Caucasian

Success
(without

Success
(with

209/263
(79.5%)

47

155/219
(70.8%)

48

6/8

(75.0%)

4/7

(57.1%)

140/205
(68.3%)

103/159
(64.8%)

7/15

(46.7%)

5/12

(41.7%)

248/311
(79.7%)

190/262
(72.5%)

10/12

(83.3%)

8/11

(72.7%)

155/206

(75.2%)

102/162

(63.0%)

3/5

(60.0%)

1/4

(25.0%)

109/168
(64.9%)

76/126

(60.3%)

6/14

(42.9%)

5/9

(55.6%)

190/249
(76.3%)

128/199
(64.3%)

Secondary Effectiveness Analysis
Table 20 describes the results of the secondary effectiveness endpoints at 24 and 84 months.

At 84 months, non-inferiority of the investigational treatment compared to the control treatment
was established in NDI success, neck pain success, arm pain success, SF-36 PCS and MCS
successes at 84 months following surgery with posterior probability of non-inferiority being
essentially 100.0% for all these endpoints. In addition, superiority was established for SF-36
MCS success at 84 months with posterior probability of superiority being 96.9%. NDI success

43

The 95% CI was provided using Frequentist Farrington and Manning methods

44

The 95% CI was provided using Frequentist Farrington and Manning methods

45

A success is a patient who had successes in NDI and neurological status and had no additional surgery classified as ‘failure’

and no severe device or device/surgery associated adverse event.

46

A success is a patient who had successes in NDI, neurological status, and FSU and had no additional surgery classified as

‘failure’ and no severe device or device/surgery associated adverse event.

47

A success is a patient who had successes in NDI and neurological status and had no additional surgery classifi ed as ‘failure’

and no severe device or device/surgery associated adverse event.

48

A success is a patient who had successes in NDI, neu ro logical status, and FSU and had no additional surgery classified as

‘failure’ and no severe device or device/surgery associated adverse event.

6/8

(75.0%)

2/7

(28.6%)

Medtronic Page 45 of 103

rates following surgery were 86.1% in the investigational group and 80.1% in the control group.
Neck pain success rates were 94.7% in the investigational group and 95.6% in the control group
and arm pain success rates were 94.2% in the investigational group and 92.8% in the control
group. The success rates of SF-36 PCS in the investigational and control groups were 85.3% and

79.2% and success rates for SF-36 MCS in the investigational and control groups were 77.0%
and 70.2% at 84 months, respectively.

At 120 months, in the investigational group, the success rate of NDI was 87.9%, neck pain
success rate was 97.3%, arm pain success rate was 94.7%. The success rates of SF-36 PCS and
MCS were 82.3% and 77.7% respectively. Statistical improvements (p<0.001) in NDI, neck/arm
pain scores were achieved at 6 weeks and maintained up to 84 months in control group and
through 120 months in the investigational group, and SF-36 PCS/MCS scores were improved
significantly from 6 months up to 84 months in control group and up to 120 months in the
investigational group (note: SF-36 PCS/MCS scores weren't assessed at postoperative until 6
months).

Medtronic Page 46 of 103

120-Month

Rate

Prestige

Cohort

IDE

Control

Prestige

Cohort

(3.7%)

(2.7%)

(3.7%)

(5.0%)

(16.3%)

(13.9%)

(22.3%)

(30.6%)

Patient

improved

Good

(22.9%)

(31.4%)

(0.7%)

(0.5%)

Work

work

Table 20: Secondary Endpoints and Other Measurements49

IDE PAS

Variable

Neck pain

Success
Failure

Arm pa in

Success
Failure

SF-36 PCS

Success
Failure

SF-36
MCS

Success
Failure

Perceived
Effect

Complete
recovery
Much

24-Month
Observed

Success Rate

LP™

IDE

260

(96.3%)

10

258

(96.3%)

10

221

(83.7%)

43

205

(77.7%)

59

127

(47.0%)

107

(39.6%)

ACDF

Control

213

(97.3%)

6

208

(95.0%)

11

186

(86.1%)

30

150

(69.4%)

66

88

(40.2%)

89

(40.6%)

24-Month Posterior Mean

(95% HPD Credible Interval)

IDE

Cohort

96.4%

(94.0%,

98.4%)

96.7%

(94.4%,

98.6%)

82.8%

(78.0%,

87.4%)

78.7%

(73.5%,

83.6%)

Not

Available

ACDF

Control

97.3%

(95.1%,

99.2%)

94.7%

(91.6%,

97.5%)

87.6%

(82.7%,

91.8%)

68.2%

(61.7%,

74.7%)

Not

Available

Cohort –

ACDF

-1.0%

(-4.3%,

2.3%)

1.9%

(-1.8%,

5.8%)

-4.7%

(-11.3%,

2.1%)

10.5%

(2.0%,

19.0%)

Not

Available

84-Month

Observed

Success Rate

LP™

PAS

196

(94.7%)

11

(5.3%)

195

(94.2%)

12

(5.8%)

174

(85.3%)

30

(14.7%)

157

(77.0)

47

(23.0)

121

(58.2%)

58

(27.9%)

ACDF

Control

172

(95.6%)

8

(4.4%)

167

(92.8%)

13

(7.2%)

141

(79.2%)

37

(20.8%)

125

(70.2%)

53

(29.8%)

71

(39.2%)

69

(38.1%)

84-Month Posterior Mean (95% HPD

Credible Interval)

PAS Cohort ACDF Control

94.5%

(91.1%,

97.4%)

94.5%

(91.3%,

97.5%)

85.0%

(80.1%,

90.0%)

78.1%

(72.1%,

83.7%)

Not Available Not Available Not Available

96.1%

(93.1%, 98.6%)

92.6%

(88.3%, 96.2%)

79.8%

(73.5%, 85.9%)

69.0%

(61.5%, 76.1%)

PAS Cohort –

ACDF

Control

-1.6%

(-6.0%, 2.9%)

1.9%

(-3.3%, 7.2%)

5.2%

(-3.4%,

13.2%)

9.1%

(-0.6%,

18.7%)

Observed

Success

Prestige

LP™ PAS

Cohort

219

(97.3%)

6

(2.7%)

213

(94.7%)

12

(5.3%)

181

(82.3%)

39

(17.7%)

171

(77.7%)

49

(22.3%)

138

(61.6%)

67

(29.9%)

Doctor
Perception

Excellent

Gait

Success
Failure

194

(71.6%)

62

268

(99.3%)

2

125

(56.8%)

69

219

(99.5%)

1

Not

Available

Not

Available

Not

Available

Not

Available

Not

Available

Not

Available

139

(66.8%)

53

(25.5%)

203

(98.5%)

3

(1.5%)

109

(59.9%)

42

(23.1%)

179

(98.4%)

3

(1.6%)

Not Available Not Available Not Available

Not Available Not Available Not Available

Status

Median
days until

40 61

Not

Available

Not

Available

Not

Available

NA NA Not Available Not Availa ble Not Av aila ble NA

return to

For patients receiving the Prestige LP™ Cervical Disc device, the mean angular motion values at
12, 24 and 84 months postoperative, respectively, were 7.85° (n=266), 7.51° (n=264) and 6.77°
(n=208) as compared to a preoperative value of 5.67° (n=260). The range of motion values
measured from flexion/extension radiographs at 24 and 84 months for the Prestige LP™ Cervical
Disc patients are presented in the histograms below. This histogram uses values obtained by
rounding the recorded range of motion for each subject to the nearest integer. The angular
motion mean was maintained in the investigational group from preoperative (5.67°) through 120
months (6.85°). In the control group, the angular motion was 7.87° at preoperative. The
postoperative angular motion, ranging from 0.31º to 0.53º, decreased significantly (p<0.001)

144

(64.0%)

67

(29.8%)

221

(98.7%)

3

(1.3%)

49

Patient accounting in this table is affected by subjects lost to follow up and/or missing data.

Medtronic Page 47 of 103

from preoperative, which indicated loss of motion for the cervical disc at the index level due to
fusion. The mean translatory motion was consistent throughout the postoperative course at the
index level for both treatment groups. The angular motion was higher in the investigational
group only at superior (but not inferior) adjacent level.

Figure 2: Histogram of Prestige LP™ Cervical Disc Angular Range of Motion at 24

Months

Figure 3: Histogram of Prestige LP™ Cervical Disc Angular Range of Motion at 84

Months

Table 21 presents data on change in range of motion from the preoperative baseline for each

time point by treatment group.

Medtronic Page 48 of 103

Prestige LP™ IDE

(N = 280)

Control

(N = 265)

Prestige LP™ PAS

(N = 280)

Control

(N = 265)

(96.6%)

(95.3%)

(83.8%)

(96.9%)

IDE

PAS

Time Point

Prestige LP™

(N =280)

Control

Time Point

Prestige LP™

(N =280)

Control

Increased (≥2º)

6 Weeks

120 (48.0%)

2 (1.4%)

36 Months

103 (48.4%)

1 (0.9%)

No Change (-2º to 2º)

70 (28.0%)

5 (3.4%)

66 (31.0%)

5 (4.7%)

Decreased ≤-2º)

60 (24.0%)

138 (95.2%)

44 (20.7%)

100 (94.3%)

Increased (≥2º)

3 Months

128 (51.0%)

0 (0.0%)

60 Months

87 (48.3%)

0 (0.0%)

No Change (-2º to 2º)

71 (28.3%)

10 (6.4%)

53 (29.4%)

7 (5.7%)

Decreased ≤-2º)

52 (20.7%)

146 (93.6%)

40 (22.2%)

116 (94.3%)

Increased (≥2º)

6 Months

119 (49.2%)

0 (0.0%)

84 Months

84 (44.0%)

0 (0.0%)

No Change (-2º to 2º)

72 (29.8%)

8 (5.3%)

60 (31.4%)

6 (5.1%)

Decreased ≤-2º)

51 (21.1%)

144 (94.7%)

47 (24.6%)

112 (94.9%)

Increased (≥2º)

12 Months

131 (52.4%)

0 (0.0%)

120 Months

94 (45.6%)

-

No Change (-2º to 2º)

71 (28.4%)

5 (3.5%)

49 (23.8%)

-

Decreased ≤-2º)

48 (19.2%)

138 (96.5%)

63 (30.6%)

-

Increased (≥2º)

24 Months

118 (48.2%)

0 (0.0%)

No Change (-2º to 2º)

68 (27.8%)

7 (5.0%)

Decreased ≤-2º)

59 (24.1%)

134 (95.0%)

Table 21: Time Course of Radiographic Change in Range of Motion

Change in Angular

Range of Mot ion

IDE

(N=265)

PAS

(N=265)

Table 22 presents radiographic disc height success at each time point for each treatment group.

Disc height (FSU) success is achieved when the change in the six-week post-operative height is
greater than or equals -2mm in either the anterior or posterior measurements. Disc height success
was similar between the two treatment groups of the patients in both groups achieving success at
each time point. Both treatment groups achieved greater than 90% success until 84 months. At
84 and 120 months, the FSU height success was 83.8% and 75.6%.

Table 22: Time Course of Radiographic Disc Height Success50

IDE PAS

Time Point

3 Months

6 Months

12 Months

229/235
(97.4%)

227/230
(98.7%)

225/233

182/182

(100.0%)

174/175
(99.4%)

164/172

Time Point

36 Months

60 Months

84 Months

178/195
(91.3%)

147/162
(90.7%)

134/160

118/120
(98.3%)

128/134
(95.5%)

123/127

24 Months

205/224
(91.5%)

156/164
(95.1%)

120 Months

124/164
(75.6%)

-

Available radiographs for the Prestige LP™ study patients were assessed for bridging bone
(Criteria was comparable to Class IV assessment on the McAfee and Mehren classification
system for Heterotopic Ossification) between the vertebral bodies of the implanted motion
segment. Bridging was defined as evidence of a continuous bony connection from the superior
vertebral body to the inferior vertebral body laterally, anteriorly, and/or posteriorly. The
radiographic results are shown in Table 23. More than 90% of the Prestige LP™ IDE patients
displayed no signs of bridging bone at each time point until 36 months, with 94.1% of the

50

Disc height success is defined as Postoperative Height minus Six-Week Postoperative Height ≥ -2mm either at the anterior or

posterior measurements

Medtronic Page 49 of 103

IDE

PAS

36 Months

Yes

0 (0%)

Yes

22 (9.5%)

No

274 (99.6%)

60 Months

No

177 (89.8%)

Yes

1 (0.4%)

Yes

20 (10.2%)

Yes

2 (0.7%)

Yes

27 (13.0%)

No

269 (98.2%)

120 Months

No

192 (85.7%)

No

253 (94.1%)

Prestige LP™ IDE Cohort

Prestige LP™ Safety Cohort

Prestige LP™ PAS Cohort

Prestige LP™ Safety Cohort

24-Month

84-Month

No

(N=253)

No

(N=303)

No

(N=181)

No

(N=226)

Patients w/

20º

% Patients

ROM ≤ 4º

67/248

(27.0%)

14/16

(87.5%)

81/264

(30.7%)

77/298

(25.8%)

15/18

(83.3%)

92/316

(29.1%)

44/180

(24.4%)

26/27

(96.3%)

70/207

(33.8%)

60/225

(26.7%)

27/28

(96.4%)

87/253

(34.4%)

% Patients

ROM > 20º

2/248

(0.8%)

0/16

(0.0%)

2/264

(0.8%)

2/298

(0.7%)

0/18

(0.0%)

2/316

(0.6%)

1/180

(0.6%)

0/27

(0.0%)

1/207

(0.5%)

1/225

(0.4%)

0/28

(0.0%)

1/253

(0.4%)

No

(N=192)

No

(N=235)

138/190
(72.6%)

0/30

(0.0%)

138/220
(62.7%)

172/233
(73.8%)

1/32

(3.1%)

173/265
(65.3%)

51//190

(26.8%)

30/30

(100.0%)

81/220

(36.8%)

59/233

(25.3%)

31/32

(96.9%)

90/265

(34.0%)

1/190

(0.5%)

0/30

(0.0%)

1/220

(0.5%)

2/233

(0.9%)

0/32

(0.0%)

2/265

(0.8%)

patients exhibiting no bridging bone at 24 months, 87.0% at 84 months and 85.7% at 120
months.

Table 23: Time Course of Bridging Bone

Bridging Bone

6 Weeks

Prestige LP™ IDE

(N = 280)

No 278 (100.0%)

Bridging

Bone

Prestige LP™ PAS

(N = 280)

No 210 (90.5%)

3 Months

6 Months

12 Months

24 Months

No 268 (99.3%) 84 Months No 181 (87.0%)

Yes 5 (1.8%) Yes 32 (14.3%)

Yes 16 (5.9%)

The percentage of Prestige LP™ patients with range of motion >4º and ≤ 20º for patients with
and without bridging bone at 24, 84, and 120 months is described in Table 24.

Table 24: Range of Motion (ROM) by Patients with Bridging Bone

4º < ROM ≤

Bridging

Bone

179/248
(72.2%)

Bridging

Bone

(N=16)

2/16

(12.5%)

Total

(N=269)

181/264
(68.6%)

Bridging

219/298
(73.5%)

Bone

Bridging

Bone

(N=18)

3/18

(16.7%)

Total

(N=321)

222/316
(70.3%)

Bridging

Bone

135/180

(75.0)

Bridging

Bone

(N=27)

1/27

(3.7%)

Total

(N=208)

136/207
(65.7%)

Bridging

Bone

164/225
(72.9%)

Bridging

Bone

(N=28)

1/28

(3.6%)

165/253
(65.2%)

Total

(N=254)

An analysis of the correlation between the degree of segmental motion, NDI, neck and arm pain
scores was also performed, and statistically significant correlations were noted, but the magnitudes
of the correlations were small.

Study Strength and Limitations

The following are important study design strengths of the IDE study as well as the post-approval
study:

▪ The PAS provided extended term profile of safety and effectiveness as well as functional data

established on a multicenter, controlled clinical trial.

▪ The consistency of data gathering approaches and endpoints was maintained through both the

Medtronic Page 50 of 103

120-Month

Bridging

Bone

Bridging

Bone

(N=32)

Total

(N=224)

Bridging

Bone

Bridging

Bone

(N=34)

Total

(N=269)

IDE and the PAS studies.

▪ The strength and reliability of the final IDE and PAS conclusions were confirmed by several

sensitivity analyses.

▪ The study design minimized potential biases by integrating a wide variety of assessments

including subjective data, physician-judged and core laboratory-assessed evaluations.

The following potential study design limitations should also be considered when interpreting the
results of the IDE study as well as the post-approval study:
▪ The study was not a randomized study as a historical control was utilized. However, even
though this study used a historical control, propensity score methods were used to adjust the
difference in the baseline variables.
▪ Although overall success (without FSU) data was available for 81.3% of all subjects at 24
months, due to the long-term nature of the IDE and the post-approval studies, progressive lower
follow-up rates at each subsequent follow-up visit through 84 months were anticipated, which
may affect interpretation of long-term study results.

▪ Several of the primary and secondary study endpoints are subjective (e.g., NDI, pain scores,

SF-36), and this subjectivity may present biases.

▪ The capability to evaluate device performance for individual segments of the subject population

is limited. This limitation is mainly because the study was not designed to assess performance
among subgroups. Any subgroup analyses should be evaluated with caution.

Conclusions Drawn from the Study Data

The clinical results from the use of the investigational device, the Prestige LP™ Cervical Disc,
were shown to be statistically non-inferior to the control group results. The scientific evidence
that has been presented here supports the safety and effectiveness of the Prestige LP™ Cervical
Disc in the treatment of intractable radiculopathy and/or myelopathy at a single-level from C3 to
C7. The study demonstrated that the treatment of intractable radiculopathy and/or myelopathy
with the Prestige LP™ Cervical Disc was as effective as the control treatment (fusion with bone
graft and plate stabilization). The results for the primary effectiveness outcome parameters for
the investigational group were non-inferior to the control group. The investigational group
demonstrated superiority to the control group for the neurological component and overall success
(without FSU) at both 24 and 84 months. Non-inferiority and superiority of the investigational
group over the control group cannot be claimed for overall success (with FSU). However, these
were established for overall success (with FSU) at 36 and 60 months. Therefore, the primary
clinical study objective was met, indicating that the Prestige LP™ Cervical Disc is as safe and
effective in the long term as the current standard of care for treating symptomatic cervical
degenerative disc disease. The Prestige LP™ Cervical Disc was able to achieve comparable or
better clinical performance while maintaining motion at the involved cervical level.

Compared to controls, the investigational group preoperatively had less subjects with abnormal
Gait (Nurick’s Classification, Grade 0-5) and positive Foraminal Compression test, but more
subjects with abnormal Motor function. As this study used historical control, propensity score
method was used to adjust the difference in the baseline variables. Hence even though there are
differences in these baseline variables, these differences do not impact the conclusion of the

study.

Medtronic Page 51 of 103

SUMMARY OF THE TWO-LEVEL IDE AND POST-APPROVAL STUDY (PAS)
METHOD

The clinical investigation of the Prestige LP™ Cervical Disc for use at two contiguous levels
was conducted under an approved IDE #G050202. The study was a prospective, multi-center,
randomized (1:1), unmasked, concurrently controlled, non-inferiority clinical trial conducted in
the United States to compare the safety and effectiveness of the 2-level Prestige LP™ Cervical
Disc to the standard of care, 2-level anterior cervical discectomy and fusion (ACDF) using
structural allograft and stabilization with an Atlantis™ Anterior Cervical Plate.

The study included a total of 397 subjects (209 investigational subjects and 188 control group
subjects) at 30 investigational sites in the United States.

Study Objectives
IDE Study

The primary objective of the IDE study was to demonstrate that the overall success rate
associated with the use of the investigational Prestige LP™ Cervical Disc is statistically non­inferior to (i.e., no worse than by a prespecified margin [10%]) the rate for the control treatment
at 24 months following surgery. Overall success was the primary endpoint for the clinical trial.

Secondary objectives were to compare the success rates of the individual effectiveness endpoints
and neurological status. The comparisons were made to determine if the investigational treatment
was statistical non-inferiority to the control treatment for each of the individual endpoints. If the
investigational treatment was found to be statistically non-inferior to the control treatment,
statistical superiority of the investigational treatment to the control treatment was also evaluated
for the individual endpoints. In addition, superiority test was performed for the overall success if
non-inferiority has been demonstrated. Statistical comparisons of operative measurements and
safety measurements was also performed.

PAS Study

The purpose of the post-approval study (PAS) was to assess long-term performance of the
Prestige LP Cervical Disc in treatment of patients with intractable cervical radiculopathy and/or
myelopathy. The primary objective was to show the overall success rate in the investigational
group is non-inferior to the success rate in the control group at 10 years after surgery.

If non-inferiority in overall success was established, superiority was evaluated as one of
secondary objectives. Other secondary objectives were to compare the success rates of the
individual efficacy endpoints and neurological success. Comparisons were made to determine if
the investigational treatment was statistical non-inferior to the control treatment for each of the
individual endpoints. If the investigational treatment was found to be statistically non-inferior to
the control treatment, statistical superiority of the investigational treatment to the control
treatment was also to be evaluated for the individual endpoints.

Study Designs
IDE Study

The IDE study was a prospective, multi-center, randomized (1:1), unmasked, concurrently
controlled, non-inferiority clinical trial conducted in the United States comparing the

Medtronic Page 52 of 103

investigational Prestige LP™ Cervical Disc treatment to the control treatment. Data were
collected at pre-operative, discharge, 6 weeks, 3 months, 6 months, 12 months (1 year) and at 24
months (2 years).

PAS Study

The post-approval study was a prospective study to continue follow-up on the subjects who
participated in the IDE study. Data were collected at 36 months (3 years), 60 months (5 years),
84 months (7 years) and 120 months (10 years) postoperative to determine the long-term safety
and effectiveness of the device.

Clinical Incl us io n and Exclusion Cr ite r ia

To qualify for enrollment in the study, subjects had to meet all of the following inclusion criteria
and none of the following exclusion criteria.

Clinical Inclusion Criteria

Enrollment in the 2-level Prestige LP™ Cervical Disc study was limited to subjects who
met the following inclusion criteria:

• Cervical degenerative disc disease at two (2) adjacent cervical levels (from C3-

C7) requiring surgical treatment and involving intractable radiculopathy,
myelopathy, or both;

• Herniated disc and/or osteophyte formation at each level to be treated that is

producing symptomatic nerve root and/or spinal cord compression. The condition
is documented by patient history (e.g., neck and/or arm pain, functional deficit
and/or neurological deficit), and the requirement for surgical treatment is
evidenced by radiographic studies (e.g., CT, MRI, x-rays, etc.);

• Unresponsive to non-operative treatment for approximately six weeks or has the

presence of progressive symptoms or signs of nerve root/spinal cord compression
in the face of continued non-operative management;

• No previous surgical intervention at the involved level or any subsequent,

planned/staged surgical procedure at the involved or adjacent level(s);

• At least 18 years of age and be skeletally mature at the time of the surgery;

• Pre-operative Neck Disability Index (NDI) score ≥ 30;

• Pre-operative neck pain score ≥ 8 on Preoperative Neck and Arm Pain

Questionnaire;

• If a female of child-bearing potential, subject is non-pregnant, non-nursing, and

agrees not to become pregnant during the study period;

• Willing to comply with the study plan and sign the Patient Informed Consent

Form.

Clinical Exclusion Criteria

Subjects were not permitted to enroll in the 2-level Prestige LP™ Cervical Disc study if
they met any of the following exclusion criteria:

• A cervical spinal condition other than symptomatic cervical disc disease requiring

surgical treatment at the involved levels;

Medtronic Page 53 of 103

• Documented or diagnosed cervical instability relative to adjacent segments at

either level, defined by dynamic (flexion/extension) radiographs showing sagittal
plane translation > 3.5 mm or sagittal plane angulation > 20°;

• More than two cervical levels requiring surgical treatment;

• A fused level adjacent to the level to be treated;

• Severe pathology of the facet joints of the involved vertebral bodies;

• Previous surgical intervention at either one or both of the involved levels or at

adjacent levels;

• Previously diagnosed with osteopenia or osteomalacia;

• Any of the following that may be associated with a diagnosis of osteoporosis (if

“Yes” to any of the below risk factors, a DEXA Scan will be required to
determine eligibility):

o Postmenopausal non-Black female over 60 years of age who weighs less

than 140 pounds.

o Postmenopausal female that has sustained a non-traumatic hip, spine, or

wrist fracture.

o Male over the age of 70;
o Male over the age of 60 that has sustained a non-traumatic hip or spine

fracture;

If the level of bone mineral density (BMD) was a T score of -3.5 or lower (i.e., -

3.6, -3.7, etc.) or a T score of -2.5 or lower (i.e., -2.6, -2.7, etc.) with vertebral
crush fracture, then the subject was excluded from the study;

• Presence of spinal metastases;

• Overt or active bacterial infection, either local or systemic;

• Insulin dependent diabetes;

• A tobacco user who does not agree to suspend smoking prior to surgery;

• Chronic or acute renal failure or prior history of renal disease;

• A documented allergy or intolerance to stainless steel, titanium, or a titanium

alloy;

• Mentally incompetent (If questionable, obtain psychiatric consult);

• A prisoner;

• Pregnant;

• An alcohol and/or drug abuser currently undergoing treatment for alcohol and/or

drug abuse;

• Involved with current or pending litigation regarding a spinal condition;

• Received drugs which may interfere with bone metabolism within two weeks

prior to the planned date of spinal surgery (e.g. steroids or methotrexate)
excluding routine perioperative anti-inflammatory drugs;

• A history of an endocrine or metabolic disorder known to affect osteogenesis

(e.g., Paget’s Disease, renal osteodystrophy, Ehlers-Danlos Syndrome, or
osteogenesis imperfecta);

• A condition that requires postoperative medications that interfere with the

stability of the implant, such as steroids. (This does not include low dose aspirin
for prophylactic anticoagulation and routine perioperative anti-inflammatory
drugs);

Medtronic Page 54 of 103

Pre-/Peri-operative

Post-operative

Pre-op

Surgery/

6 wks

3 mos

6 mos

12 mos,

(±2 mos)

60 mos, 84

(±3 mos)

Clinical Evalu at i on s :

Inclusion/Exclu sion Determination

X

Osteoporosis/Osteopenia Screen

X

Informed Consent and HIPAA
Authorization

X

Baseline Medical History/Physical
Exam

X

Surgery and Hospital Discharge
Data

X
Neck Disability Inde x (NDI)

X X X X X X

Neck and Arm Pain Questionnaire

X X X X X X

Health Status Questionnaire (SF-36)

X X X X

Neurological Status

X X X X X X

• Received treatment with an investigational therapy within 28 days prior to

implantation surgery or such treatment is planned during the 16 weeks following
implantation with the Prestige LP™ device.

Study Population

The study included a total of 397 subjects (209 investigational subjects and 188 control group
subjects).

Post-operative Care

The recommended post-operative care included avoidance of overhead lifting, heavy lifting,
repetitive neck bending, and high-impact exercise or athletic activity for 60 days post­operatively. Avoidance of prolonged (beyond 2 weeks post-op) non-steroidal anti-inflammatory
drug (NSAID) use was specified, although the use of NSAIDs was recommended for the first
two weeks post-operatively in the 2-level Prestige LP™ Cervical Disc group. Post-operative
bracing requirements were left to the discretion of the investigators and included the option for
use of a soft collar as needed. Subjects who smoked were encouraged to discontinue smoking.
The use of electrical/external bone growth stimulators was not recommended during the 24­month follow-up period. However, in the few control group cases where an electric al/external
bone growth stimulator was used, the subjects were deemed treatment failures.

Study Visits and Length of Follow-Up

For the IDE study, patients were evaluated pre-operatively (within 6 months of surgery), intra­operatively, immediately post-operatively (prior to discharge) and then at 6 weeks, 3, 6, 12, 24
months, and annually thereafter until the last subject enrolled in the study had been seen for their
24-month evaluation. For the PAS, patients were evaluated at 36, 60, 84 and 120 months.
Effectiveness parameters assessed during follow-up included pain and function measured by the
Neck Disability Index (NDI), neck pain, arm pain, and quality of life as measured by the Medical
Outcomes Study 36-Item Short Form Health Survey (SF-36). Other parameters assessed during
follow-up included neurological assessment and radiologic outcomes. The length of follow-up
for individual subjects was up to 120 months (10 years). Complications and adverse events,
device-related or not, were evaluated over the course of the study. Evaluations were done
according to the visit schedule below:

Table 25: Schedule of Study Assessments

Procedure

Medtronic Page 55 of 103

Hospital
Discharge

(±2 wks)

(±2 wks)

(±1 mo)

24 mos
36 mos,

mos, 120
mos

Pre-/Peri-operative

Post-operative

Pre-op

Surgery/

6 wks

3 mos

6 mos

12 mos,

(±2 mos)

60 mos, 84

(±3 mos)

Preoperative Gait Assessment and
Foraminal Compressi on Test

X X X X X X
Medication Use

X X X X X X

Work Status

X X X X X X

Satisfaction and Perceived Effect
(subject & physician)

X X X X X X
Radiologic Review

X X X X X X X

Adverse Events

X X X X X X

Subject Disposition*

X X X X X X X

Radiographic Proc ed u res

Anterior/Posteri or an d Lat er a l
Neutral X-rays

X X X X X X X
Lateral Flexi o n/Extension X-rays

X X X X X X

CT and/or MRI

X

DEXA Scan **

X

Procedure

* While the Subject Disposition CRF could be filled out at any time, it was only filled out once for each subject.
** A DEXA Scan was only required if the subject had a risk factor that may be associated with a diagnosis of osteoporosis as outlined in the
clinical proto co l.

Hospital
Discharge

(±2 wks)

(±2 wks)

(±1 mo)

24 mos
36 mos,

mos, 120
mos

Data Source

New data collection

IDE and PAS Key Study Endpoints

The safety of the 2-level Prestige LP™ Cervical Disc was assessed by comparing the nature and
frequency of adverse events (overall and in terms of seriousness and relationship to the device
and/or procedure) and subsequent surgical procedures as well as maintenance or improvement in
neurological status to the 2-level ACDF control group.

The effectiveness of the 2-level Prestige LP™ Cervical Disc was assessed by evaluating
improvement in NDI score, improvement in neck and arm pain measured at rest using a neck and
arm pain questionnaire, improvement in quality of life measured using the Short-Form 36 (SF-

36) questionnaire, subject satisfaction, medication usage, and work status compared to the 2­level ACDF control group.

In addition, several radiographic endpoints were considered in evaluating both safety and
effectiveness including range of motion, functional spinal unit (FSU) height maintenance,
implant condition, and heterotopic ossification.

Per the IDE and PAS protocol, an individual subject in either treatment group was considered an
overall success if the following criteria were met at 24 months for IDE and 120 months for the
PAS post-operative.

1. Improvement (reduction) of at least 15 points in NDI score compared to pre-operative

baseline;

2. Maintenance or improvement in neurological status compared to pre-operative baseline

as measured based on motor function, sensory function, and reflexes;

3. No serious adverse event classified as implant associated, or implant/surgical procedure

associated; and

4. No additional surgical procedure classified as a “failure.”

Medtronic Page 56 of 103

Note that because the additional surgical procedure component of the primary endpoint did not
consider all subsequent surgeries at the index level as failures, FDA requested an additional
analysis of overall success in which all subsequent surgeries at the index level and all intra­operative treatment conversions were considered failures.

Overall study success criteria were based on a comparison of individual subject success rates,
such that the subject success rate for the 2-level Prestige LP™ group was required to be non­inferior to that of the 2-level ACDF control group. The study was designed as a non-inferiority
study with a margin (delta) of 10%. For the analysis of overall success at 24 months, individual
effectiveness endpoints at 24 months and neurological success at 24 months, a Bayesian analysis
model incorporated data from both the 12-month and 24-month follow-up visits, including data
from the 12- only or 24-month only visits, to statistically compare the outcomes at the 24-month
visit between the two treatment groups. The study hypothesis was that the success rate of the 2­level Prestige LP™ group was statistically non-inferior to the success rate in the 2-level ACDF
control group by a margin of 10%. Non-inferiority was to be claimed if the posterior probability
that the success rate in the 2-level Prestige LP™ group was not lower than the success rate in the
2-level ACDF control group by more than 10% was greater than 95%. For comparison of
adverse events and subsequent surgical procedures, a beta-binomial model was used.

Secondary effectiveness endpoints, measured in both treatment groups at 24 months, included
neck pain success, arm pain success, quality of life (SF-36 Physical Component Score [PCS]
success and Mental Component Score [MCS] success), gait assessment (Nurick’s classification)
success and Functional Spinal Unit (FSU) height success were compared using the Bayesian
model described above. Additional measurements included subject satisfaction, subject
perceived effect, physician perception of results, radiographic success (defined differently in the
two treatment groups), range of motion, implant condition, heterotopic ossification, and return to
work were summarized by group.

For the PAS study (post 24 months to 120 months), overall success, individual effectiveness
endpoints and neurological success at 36, 60, 84 and 120 months were compared using a
Bayesian beta-binomial model. For safety endpoints, including adverse events and secondary
surgeries up to 120 months, a Bayesian Cox proportional hazard model was used to compare the
rates of AEs and the secondary surgeries at index and adjacent levels between the investigational
group and the control group. The cumulative rates were derived using life-table method.

In addition, for the PAS study, continuous effective scores, including improvement of NDI, neck
pain, arm pain, SF-36 PCS and SF-36 MCS score from baseline at 36 months, 60 months, 84
months and 120 months were compared using a Bayesian normal model.

Multiple comparisons were carried out without adjusting for multiplicity.

Total number of Enrolled Study Sites and Subjects, Follow-up Rate

A total of 81 investigators and sub-investigators participated at 30 investigational sites in the
United States. A total of 397 subjects (209 2-level Prestige LP™, 188 2-level ACDF control)
enrolled in the study. At the time of database lock, of the 397 subjects enrolled in the study,
complete 24-month overall success (primary endpoint) data was available for 199 2-level
Prestige LP™ subjects (95.2%) and 160 2-level ACDF control subjects (88.9%). In addition,

Medtronic Page 57 of 103

12 Months

24 Months

36 Months

60 Months

84 Months

120 Months

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

Enrolled and treated

209

188

209

188

209

188

209

188

209

188

209

188

Deaths (cumulative)

0 0 0 0 0 1 1 1 2 2 2

3

Subject Absence Due to

at 120 Months

Theoretica l F ollow-up1

209

188

209

188

209

188

209

188

209

188

181

160

Withdrawn
(cumulative)

Expected

2

209

184

209

180

209

177

203

175

201

172

172

139

Actual, primary

follow-up)

Actual, primary

window (% follow-up)4

Actual, any data (%
follow-up)

204

(97.6%)

168

(91.3%)

199

(95.2%)

164

(91.1%)

187

(89.5%)

153

(86.4%)

167

(82.3%)

140

(80.0%)

154

(76.6%)

127

(73.8%)

148

(86.0%)

118

(84.9%)

complete 120-month overall success (primary endpoint for PAS study) data was available for
147 2-level Prestige LP™ subjects (85.5%) and 118 2-level ACDF control subjects (84.9%). A
summary of subject accountability data (includes subjects evaluated and percent follow-up rate)
are presented in Table 26.

Table 26: Subject Accountability

Sites Not Participating

endpoint data (%

endpoint data in

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF contro l (N=188)

1

Theoretical Follow-up = Enrolled and Treated – Subject Absence Due to Sites Not Participating at 120 Months

2

Expected = Theoretical – Cumulative Deaths – Cumulative Withdrawal

3

Subjects with complete data for the primary endpoint (overall success), regardless of in-window status.

4

Subjects with complete data for the primary endpoint (overall success), evaluated in-window. Actual, primary endpoint data in window /

Enrolled & Treated = % follo w

5

Subjects with any follow-up data revie w ed or evaluated.

3

5

0 0 0 0 0 0 0 0 0 0 28 28

0 4 0 8 0 10 5 12 6 14 7 18

202

(96.7%)

191

(94.6%)

166

(90.2%)

162

(97.6%)

199

(95.2%)

181

(91.0%)

160

(88.9%)

140

(87.5%)

185

(88.5%)

148

(80.0%)

150

(84.7%)

124

(82.7%)

167

(82.3%)

119

(71.3%)

139

(79.4%)

97

(69.8%)

154

(76.6%)

136

(88.3%)

127

(73.8%)

116

(91.3%)

147

(85.5%)

103

(69.6%)

118

(84.9%)

86

(72.3%)

In addition to the study subjects described above, there were an additional 59 subjects (17 2-level
Prestige LP™ subjects and 42 2-level ACDF control subjects) who were con sen ted and
randomized but declined participation in the study prior to receiving the assigned treatment. The
demographic and preoperative characteristics of the subjects who declined to participate in this
study were comparable to the characteristics of the subjects who participated in the study.

Throughout this summary, the primary analysis dataset (209 2-level Prestige LP™ subjects, 188
2-level ACDF control subjects) includes all subjects who completed the surgical procedure and
received a study device in either treatment group classified according to the treatment received
(as-treated). Subjects who had subsequent surgical procedures classified as “failures” were
deemed “failures” for overall success, and since these subsequent surgical procedures had the
potential to alter the original study treatment’s outcomes, for all neurological status and all
individual effectiveness variables, the last observation obtained before the subsequent surgery
occurred was carried forward. Primary statistical comparisons were based on the observed data,
and missing data due to lost-to-follow-ups were not imputed. Therefore, the denominators varied
for the primary study endpoint (overall success) and individual effectiveness variables such as
NDI and neurological status.

Study Population Demographics and Baseline Parameters
Table 27 presents the summary statistics for demographic and baseline characteristics for the 2-

level Prestige LP™ group and the 2-level ACDF control group. The demographics of the study

Medtronic Page 58 of 103

INV

(N=209)

CTR

(N=188)

p-value

(INV - CTR)

Age (years; mean ± standard deviation)

47.1 ± 8.3

Range: 22 – 75

47.3 ± 7.7

Range: 25 – 69

0.844

Gender (n(%))

Female

117 (56.0%)

98 (52.1%)

0.480

Race (n(%))

Other

1 (0.5%)

1 (0.5%)

0.879

BMI (kg/m2; mean ± standard deviation)

28.2 ± 5.6

Range: 16.4 – 46.1

28.6 ± 4.9

Range: 18 – 43.4

0.481

Marital Status (n(%))

Widowed

2 (1.0%)

1 (0.5%)

0.698

Education Level (n( %))

> High School

125 (59.8%)

104 (55.3%)

0.652

Previous Neck Surgery (n(%))

No

209 (100.0%)

186 (98.9%)

0.224

Pre-operative Medicati o n Use

Muscle Relaxants

75/208 (36.1%)

73/188 (38.8%)

0.604

Pre-operative Pain Status1

Neck Pain Only

29 (13.9%)

15 (8.0%)

0.078

Pre-operative Diagnosis (n(%))

Myelopathy only

5 (2.4%)

6 (3.2%)

0.837

Duration of S ymptoms

> 6 mos.

148 (70.8%)

122 (64.9%)

0.340

Pre-operative Work Status

146 (69.9%)

113 (60.1%)

0.045

Worker’s Compensation

26 (12.4%)

19 (10.1%)

0.527

Unresolved Spinal Litigation

0 (0.0%)

1 (0.5%)

0.474

Smoking Status

Not provided. Protocol excluded tobacco use r s wh o did not agree to

stop smoking prior to surgery.

Current Alcohol Use

116 (55.5%)

88 (46.8%)

0.088

population are consistent with the demographics reported for prior cervical artificial disc studies
conducted in the U.S.

The investigational and control treatment groups were similar demographically. Although p­values were obtained without any adjustment for multiplicity, there were no statistically
significant differences (p<0.05) for any of the variables except for preoperative work status
(69.9% working pre-operatively in the 2-level Prestige LP™ group as compared to 60.1% in the
2-level ACDF control group).

Table 27: Study Population Demographics and Baseline Characteristics

Demographic Measure/ Baseline Characteristic

Male

Caucasian
Black
Asian
Hispanic

Single
Married
Divorced
Separated

< High School
High School

Yes

Non-Narcotics
Weak Narcotics
Strong Narcotics

Arm and Neck Pain
Arm Pain Only

92 (44.0%)

195 (93.3%)

8 (3.8%)
1 (0.5%)
4 (1.9%)

25 (12.0%)

146 (69.9%)

32 (15.3%)

4 (1.9%)

21 (10.0%)
63 (30.1%)

0 (0.0%)

138/208 (66.3%)

83/208 (39.9%)
52/207 (25.1%)

180 (86.1%)

0 (0.0%)

90 (47.9%)

172 (91.5%)

8 (4.3%)
3 (1.6%)
4 (2.1%)

29 (15.4%)

133 (70.7%)

23 (12.2%)

2 (1.1%)

20 (10.6%)
64 (34.0%)

2 (1.1%)

133/185 (71.9%)

78/186 (41.9%)
44/188 (23.4%)

173 (92.0%)

0 (0.0%)

0.275

0.758

0.725

Radiculopathy and myelopathy
Radiculopathy only

< 6 wks.
6 wks. – 6 mos.

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

1

Pre-operative arm and neck pain defined as both arm and neck pain scores ≥ 8/10; pre-operative neck pain only defined as neck pain
score ≥ 8/10 and arm pain score < 8/10. There were no subjects with only arm pain because neck pain score ≥ 8/10 was a study
inclusion criterion.

Medtronic Page 59 of 103

54 (25.8%)

150 (71.8%)

5 (2.4%)

56 (26.8%)

45 (23.9%)

137 (72.9%)

8 (4.3%)

58 (30.9%)

Variable

INV

(N=209)

CTR

(N=188)

p-value

(INV - CTR)

NDI; mean ± standard dev ia ti on

52.1 ± 13.4

Range: 30 – 84

53.2 ± 14.8

Range: 30 – 94

0.441

SF-36 PCS; mean ± standard de viation

31.8 ± 7.8

Range: 11.7 – 55.5

30.8 ± 7.4

Range: 11.1 – 51.1

0.189

SF-36 MCS; mean ± st andard deviation

43.9 ± 11.8

Range: 16.7 – 70.6

43.8 ± 12.2

Range: 15.9 – 67.1

0.930

Neck Pain Score; mean ± standard deviation

16.2 ± 2.9

Range: 8 – 20

16.3 ± 2.6

Range: 8 – 20

0.720

Arm Pain Score; mean ± standard deviation

13.8 ± 5.6

Range: 0 – 20

14.4 ± 4.3

Range: 0 – 20

0.208

Neurological Status Normal (n(%))

Overall1

42 (20.1%)

31 (16.5%)

0.367

ROM flexion/extension angulation (º) Superior

mean ± standard deviation

Range: 0.08 – 18.15

Range: 0.45 – 19.72

0.387

ROM flexion/extension angulation (º) Inferior

mean ± standard deviation

Range: 0.37 – 18.20

Range: 0.37 – 18.51

0.637

ROM flexion/extension translation (mm) Superior

mean ± standard deviation

Range: 0.13 – 9.17

Range: 0.03 – 8.96

0.446

ROM flexion/extension translation (mm) Inferior

mean ± standard deviation

Range: 0.06 – 3.42

Range: 0.00 – 6.60

0.267

Baseline radiographic findings – superior target

Both

98 (46.9%)

102 (54.3%)

0.240

Baseline radiographic findings – inferior target

Both

100 (47.8%)

97 (51.6%)

0.480

The mean baseline pre-operative assessments for the 2-level Prestige LP™ group and the 2-level
ACDF control group are presented in Table 28. Although p-values were obtained without any
adjustment for multiplicity, there were no statistical differences between the 2-level Prestige
LP™ group and the 2-level ACDF control group for any of the variables identified in the table.

Table 28: Preoperative Evaluation of Clinical Endpoints

Motor
Sensory
Reflexes

Target Level;

Target Level;

Target Level;

Target Level;

level (n(%))

Herniated disc
Osteophyte format ion

level (n(%))

Herniated disc
Osteophyte format ion

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

1

If at least one of the three components (motor, sensory, reflexes) is not normal, then overall is defined as not normal. If all

components are normal, then overall is defined as normal.

97 (46.4%)
85 (40.7%)
90 (43.1%)

6.75 ± 4.16

5.56 ± 3.89

1.48 ± 1.08

1.04 ± 0.74

63 (30.1%)
48 (23.0%)

67 (32.1%)
42 (20.1%)

88 (46.8%)
66 (35.1%)
75 (39.9%)

7.12 ± 4.14

5.37 ± 3.26

1.57 ± 1.14

1.14 ± 0.93

54 (28.7%)
32 (17.0%)

62 (33.0%)
29 (15.4%)

1.000

0.257

0.542

Surgery and Hospitalization Data
Table 29 summarizes the information related to the surgical procedures and postoperative

hospitalizations of subjects. The most common treated surgical levels were the C5-C6 and C6-C7
levels. The mean operative times for the 2-level Prestige LP™ and 2-level ACDF control groups
were 2.1 hours and 1.7 hours, respectively, which is a mean difference of 0.4 hours (24 minutes)
when not adjusting for multiplicity. Additionally, 2-level Prestige LP™ subjects were found to
have more estimated blood loss compared to the 2-level ACDF control group subjects (67.2 ml
for 2-level Prestige LP™ group versus 55.7 ml for 2-level ACDF control group) when not
adjusting for multiplicity. The mean hospital stays for subjects in both treatment groups were
similar (1.2 days versus 1.3 days for the 2-level Prestige LP™ and 2-level ACDF control groups,

Medtronic Page 60 of 103

Procedural Characteristic

INV

CTR

Posterior Mean and 95% BCI of the

CTR (lower, upper)

Treated Level (n(%))

C5-C6 and C6-C7

163 (78.0%)

141 (75.0%)

N/A

Operative time (hrs);
mean ± standard deviation

2.1 ± 0.8

Range: 0.8 – 5.0

1.7 ± 0.7

Range: 0.7 – 4.9

0.4 (0.25, 0.55)

Blood Loss (m l) ;

67.2 ± 64.1

(n=208)

55.7 ± 46.3

11.5 (0.56, 2 2.44)
Hospitaliz ation (days);
mean ± standard deviation

1.2 ± 0.5

Range: 0.0 – 4.0

1.3 ± 1.0

Range: 0.0 – 8.0

-0.1 (-0.26, 0.06)

Median Return to Work Time (days)

49

55

N/A

Superior Level

Prestige LP™ Size

Inferior Level

Prestige LP™ Size

C3-C4,

C4-C5

C4-C5,

C5-C6

C5-C6,

C6-C7

Total

(N=209)

5mm x 12mm

5mm x 12mm

0 1 0

1 (0.5%)

5mm x 12mm

5mm x 14mm

0 0 1

1 (0.5%)

5mm x 12mm

6mm x 14mm

0 1 0

1 (0.5%)

5mm x 14mm

5mm x 14mm

1 5 13

19 (9.1%)

5mm x 14mm

5mm x 16mm

0 0 3

3 (1.4%)

5mm x 14mm

6mm x 12mm

0 1 0

1 (0.5%)

5mm x 14mm

6mm x 14mm

0 1 9

10 (4.8%)

5mm x 14mm

6mm x 16mm

0 0 2

2 (1.0%)

5mm x 14mm

8mm x 14mm

0 0 1

1 (0.5%)

5mm x 16mm

5mm x 14mm

0 2 0

2 (1.0%)

5mm x 16mm

5mm x 16mm

2 6 15

23 (11.0%)

5mm x 16mm

6mm x 16mm

0 2 10

12 (5.7%)

6mm x 12mm

5mm x 14mm

0 1 0

1 (0.5%)

6mm x 12mm

6mm x 12mm

0 0 3

3 (1.4%)

6mm x 12mm

6mm x 14mm

0 1 0

1 (0.5%)

6mm x 12mm

7mm x 12mm

0 0 3

3 (1.4%)

6mm x 14mm

5mm x 14mm

0 0 2

2 (1.0%)

6mm x 14mm

5mm x 16mm

0 1 0

1 (0.5%)

6mm x 14mm

6mm x 12mm

0 0 1

1 (0.5%)

6mm x 14mm

6mm x 14mm

0 6 23

29 (13.9%)

6mm x 14mm

6mm x 16mm

0 1 8

9 (4.3%)

6mm x 14mm

7mm x 16mm

0 0 2

2 (1.0%)

6mm x 14mm

8mm x 14mm

0 0 1

1 (0.5%)

6mm x 14mm

8mm x 16mm

0 0 1

1 (0.5%)

6mm x 16mm

5mm x 16mm

0 1 1

2 (1.0%)

6mm x 16mm

6mm x 14mm

0 0 1

1 (0.5%)

6mm x 16mm

6mm x 16mm

0 6 25

31 (14.8%)

6mm x 16mm

7mm x 16mm

0 0 4

4 (1.9%)

6mm x 16mm

7mm x 18mm

0 0 2

2 (1.0%)

7mm x 12mm

6mm x 12mm

0 0 2

2 (1.0%)

7mm x 14mm

5mm x 14mm

0 0 1

1 (0.5%)

7mm x 14mm

6mm x 14mm

0 2 0

2 (1.0%)

7mm x 14mm

6mm x 16mm

0 0 1

1 (0.5%)

7mm x 14mm

7mm x 14mm

0 1 0

1 (0.5%)

respectively). Data regarding the amount/type of decompression and handling of the posterior
longitudinal ligament for each procedure was not systematically collected.

Table 30 summarizes the Prestige LP™ devices implanted during the 2-level clinical study by
size and treatment level.

Table 29: Surgical Data

Difference of Mean between INV and

C3-C4 and C4-C5
C4-C5 and C5-C6

mean ± standard deviation

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
BCI = Bayesian HPD Credible Interval

Table 30: Prestige LP™ Devices Implanted by Size and Treatment Level

3 (1.4%)

43 (20.6%)

Range: 0.0 – 600

3 (1.6%)

44 (23.4%)

Range: 0.0 – 250.0

Medtronic Page 61 of 103

7mm x 14mm

7mm x 16mm

0 0 1

1 (0.5%)

7mm x 16mm

5mm x 16mm

0 1 0

1 (0.5%)

7mm x 16mm

6mm x 16mm

0 0 7

7 (3.3%)

7mm x 16mm

7mm x 16mm

0 2 5

7 (3.3%)

7mm x 16mm

7mm x 18mm

0 0 1

1 (0.5%)

7mm x 18mm

7mm x 16mm

0 0 1

1 (0.5%)

7mm x 18mm

7mm x 18mm

0 1 12

13 (6.2%)

7mm x 18mm

8mm x 18mm

0 0 1

1 (0.5%)

Total (%)

3 (1.4%)

43 (20.6%)

163 (78.0%)

209 (100%)

SUMMARY OF THE IDE AND POST APPROVAL STUDY (PAS) RESULTS

Final Safety Findings (Key Endpoints)

The analysis of safety was based on the as-treated cohort of 397 total subjects which included all
subjects who completed the surgical procedure and received a study device in either treatment
group classified according to the treatment received (209 2-level Prestige LP™ subjects and 188
2-level ACDF control subjects).

Summary of Adverse Event Data:
A summary of the adverse event data is presented in Table 31. Adverse events were classified by
an independent Clinical Adjudication Committee (CAC) for severity and relationship to the
device and/or surgical procedure.

The severity of an AE was assessed as mild (grade 1), moderate (grade 2), severe (grade 3), or
life-threatening (grade 4) according to the World Health Organization (WHO) Recommendations
for Grading of Acute and Subacute Toxic Effects.

The relationship between an AE and the device/surgical procedure was assessed based on the
following definitions:

• Implant Associated: AE for which there is a reasonable possibility that the AE may have

been caused primarily by the device;

• Implant/Surgical Procedure Associated AE: AE for which there is a reasonable possibility

that the AE may have been caused both by the device and the surgical procedure;

• Surgical Procedure Associated AE: AE for which there is a reasonable possibility that the AE

may have been caused primarily by the surgical procedure;

• Undetermined: AE for which sufficient information is not available at the time of the AE to

determine its causality;

• Not Related: AE for which sufficient information exists to indicate that the etiology is

unrelated to the device or surgical procedure.

24 Months
The overall AE rates were similar in the 2-level Prestige LP™ group (93.3%) and in the 2-level
ACDF control group (92.0%) through 24 months. The 2-level Prestige LP™ group had fewer
serious (Grade 3 or 4) adverse events (34.9% versus 48.4%, posterior mean (95% Bayesian
credible interval (BCI)) of the difference of event rate: -13.4% (-22.9%, -3.7%). The 2-level
Prestige LP™ group also had statistically fewer secondary surgical interventions at the index

Medtronic Page 62 of 103

levels (2.4%) than the ACDF group (8.0%), posterior mean (95% Bayesian credible interval
(BCI)) of the difference of event rate: -5.6% (-10.2%, -1.1%).

120 Months
There is no statistical difference of adverse event rates between the two groups (98.6% versus

95.2%, posterior mean (95% Bayesian credible interval (BCI)) of log hazard ratio (LHR): 0.02 (-

0.18, 0.23)). The 2-level Prestige LP™ group had fewer serious (Grade 3 or 4) adverse events
(66.7% versus 70.9%, posterior mean (95% Bayesian credible interval (BCI)) of log hazard ratio
(LHR): -0.31 (-0.57, -0.06)) and fewer serious (Grade 3 or 4) implant- or implant/surgical
procedure-related adverse events (3.8% vs 8.1%, posterior mean (95% Bayesian credible interval
(BCI)) of log hazard ratio (LHR): -0.92 (-1.88, -0.01)) as compared to the 2-level ACDF control
group. The 2-level Prestige LP™ group also had statistically fewer secondary surgical
interventions at the index levels (4.7%) than the ACDF group (17.6%) (LHR (95% BCI): -1.39 (-

2.15, -0.61)) as well as at adjacent levels (9.0% versus 17.9%) (LHR (95% BCI): -0.66 (-1.29, -

0.01)). The posterior probability of superiority of 2-level Prestige LP™ group over 2-level
ACDF control group is almost 100% for the secondary surgeries at the index levels and 98.0%
for the secondary surgeries at adjacent levels.

Medtronic Page 63 of 103

Subsequent

Level

Subsequent

Adjacent Level

Device/Surgical

AEs

Device or

AEs

Severe Device or

AEs (Grade 3 or 4)

Table 31: Summary of Adverse Events (AEs) Up to the 120-Month Time Interval

IDE 24 Month PAS 120 Month

INV (N=209) CT R (N= 188)

Adverse Event

Type

Events

All Adverse Events 1485 195 (93.3%) 1603

Surgeries at Index

6 5 (2.4%) 17

Subjects

(n (%))

Events

Subjects

(n (%))

173

(92.0%)

15

(8.0%)

Posterior M ean

and 95% BCI* of

the Difference of

Event Rate

between INV and

CTR

1.3%

(-3.9%, 6.6%)

-5.6%

(-10.2%, -1.1%)

Events

2675 206 (98.6%) 206 (99.1%) 2669 179 (95.2%) 179 (97.3%)

11 9 (4.3%) 9 (4.7%) 33 27 (14.4%) 27 (17.6%)

INV (N=209) CTR (N=188)

Subjects

(n (cumulative

rate %))

Subjects

(n (cumulative

rate %))
life table

Events

Subjects

(n

(cumulative

rate %))

Subjects

(n

(cumulative

rate %))
life table

Posterior

Mean of log

Hazard

Ratio (95%

BCI*)

0.02

(-0.18, 0.23)

-1.39

(-2.15, -0.61)

Surgeries at

Device Related

AEs

Procedure Related

Device/Surgical

Procedure Related

Surgical Procedure

Related AEs

Severe AEs (Grade

3 or 4)

Device/Surgical

Procedure Related

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
* BCI = Bayesian HPD Credible Interval

5 5 (2.4%) 8

44 17 (8.1%) 29

61 20 (9.6%) 67

105 35 (16.7%) 96

127 60 (28.7%) 101

304 73 (34.9%) 437

15 5 (2.4%) 29

6

(3.2%)

14

(7.4%)

26

(13.8%)

37

(19.7%)

44

(23.4%)

91

(48.4%)

12

(6.4%)

-0.8%

(-4.4%, 2.6%)

0.6%

(-4.8%, 6.0%)

-4.3%

(-10.7%, 2.1%)

-2.9%

(-10.6%, 4.6%)

5.2%

(-3.3%, 13.8%)

-13.4%

(-22.9%, -3.7%)

-4.0%

(-8.4%, 0.1%)

16 16 (7.7%) 16 (9.0%) 34 24 (12.8%) 24 (17.9%)

70 36 (17.2%) 36 (23.2%) 34 18 (9.6%) 18 (10.5%)

75 25 (12.0%) 25 (12.7%) 89 32 (17.0%) 32 (18.4%)

145 55 (26.3%) 55 (31.7%) 123 44 (23.4%) 44 (25.0%)

127 60 (28.7%) 60 (28.7%) 102 44 (23.4%) 44 (23.4%)

630 124 (59.3%) 124 (66.7%) 748 120 (63.8%) 120 (70.9%)

18 7 (3.3%) 7 (3.8%) 46 14 (7 .4% ) 14 (8.1%)

-0.66

(-1.29, -0.01)

0.53

(-0.04, 1.10)

-0.41

(-0.93, 0.13)

0.04

(-0.35, 0.45)

0.23

(-0.16, 0.62)

-0.31

(-0.57, -0.06)

-0.92

(-1.88, -0.01)

Medtronic Page 64 of 103

Superior C3-C4

Inferior C4-C5

Superior C4-C5

Inferior C5-C6

Superior C5-C6

Inferior C6-C7

Superior C3-C4

Inferior C4-C5

Superior C4-C5

Inferior C5-C6

Superior C5-C6

Inferior C6-C7

Device or

Related AEs

Surgical

Related AEs

Severe Device

(Grade 3 or 4)

Adverse Event Data by Treatment Level: Table 32 provides summary adverse event data in each treatment group by treatment level, including post-hoc statistical analysis and comparison between the 2-level Prestige LP™ group and the 2-level ACDF control group through the 24-month and 120-month time point, respectively, using Frequentist methods.

Table 32: Summary of Total Adverse Events by Level Treated Through 120 Months

INV CTR INV CTR INV CTR INV CTR INV CTR INV CTR

All Adverse
Events

Statistics*

3/3

(100%)

(-26.3%, 93.0 % )

2/3

(66.7%)

33.3%

IDE 24 Month PAS 120 Month

41/43

(95.3%)

(-6.2%, 15.1%)

4.4%

40/44

(90.9%)

151/163
(92.6%)

-0.3%

(-6.1%, 5.6%)

131/141
(92.9%)

3/3

(100%)

(-26.3%, 93.0%)

(66.7%)

33.3%

2/3

43/43

(100%)

4.5%

(-1.8%, 10.8%)

42/44

(95.5%)

160/163
(98.2%)

2.4%

(-1.4%, 6.2%)

135/141
(95.7%)

Device/Surgical
Procedure

Procedure

Severe AEs
(Grade 3 or 4)

or
Device/Surgical
Procedure
Related AEs

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
* Point Esti mate and 95% Co nfidence Inte rval of Differ ence of Adverse Rate between INV and CTR . T h e 9 5 % CI was provide d using
Frequentist Farrington and Ma nning methods.

Timecourse of All Adverse Events:
The timecourse of adverse events reported in the clinical study from all 397 total subjects (209 2­level Prestige LP™ subjects and 188 2-level ACDF control subjects) through all available
follow-up are shown in Table 33a and 33b. This table includes adverse events from all subjects
to establish the safety profile of the device. Adverse events are listed in alphabetical order by
main category with clinically relevant subcategories also detailed. Definitions of the adverse
event categories and subcategories are provided in Table 34. Subject adverse event rates are
based on the number of subjects having at least one occurrence of an adverse event, divided by
the number of subjects in that treatment group. Subjects experiencing adverse events in more
than one category are represented in each category in which they experienced an adverse event.

Through 24 Months, the percentage of subjects who experienced at least one adverse event is
similar in the 2-level Prestige LP™ group (93.3%) and the 2-level ACDF control group (92.0%).
Some of the more commonly reported clinically relevant adverse events through all available
follow-up were neck and/or arm pain (in 60.8% of 2-level Prestige LP™ subjects and 61.2% of
2-level ACDF control subjects), neurological adverse events (in 43.1% of 2-level Prestige LP™
subjects and 45.7% of 2-level ACDF control subjects), cervical study surgery spinal events (in

13.9% of 2-level Prestige LP™ subjects and 9.0% of 2-level ACDF control subjects), cervical

0/3

(0.0%)

0/3

(0.0%)

2/3

(66.7%)

0/3

(0.0%)

0/3

(0.0%)

1/3

(33.3%)

0/3

(0.0%)

0/3

(0.0%)

9/43

(20.9%)

13/43

(30.2%)

17/43

(39.5%)

1/43

(2.3%)

10/44

(22.7%)

9/44

(20.5%)

20/44

(45.5%)

3/44

(6.8%)

26/163

(16.0%)

47/163

(28.8%)

54/163

(33.1%)

4/163

(2.5%)

27/141

(19.1%)

34/141

(24.1%)

71/141

(50.4%)

9/141

(6.4%)

0/3

(0.0%)

0/3

(0.0%)

2/3

(66.7%)

0/3

(0.0%)

0/3

(0.0%)

1/3

(33.3%)

0/3

(0.0%)

0/3

(0.0%)

14/43

(32.6%)

13/43

(30.2%)

24/43

(55.8%)

1/43

(2.3%)

10/44

(22.7%)

9/44

(20.5%)

27/44

(61.4%)

3/44

(6.8%)

41/163

(25.2%)

47/163

(28.8%)

98/163

(60.1%)

6/163

(3.7%)

34/141

(24.1%)

34/141

(24.1%)

93/141

(66.0%)

11/141

(7.8%)

Medtronic Page 65 of 103

Heterotopic Ossification (in 10.0% of 2-level Prestige LP™ subjects and 7.4% of 2-level ACDF
control subjects), dysphagia/dysphonia (in 6.7% of 2-level Prestige LP™ subjects and 11.2% of
2-level ACDF control subjects), non-infectious wound adverse events (in 7.2% of 2-level
Prestige LP™ subjects and 5.9% of 2-level ACDF control subjects), and implant adverse events
(in 6.2% of 2-level Prestige LP™ subjects and 5.3% of 2-level ACDF control subjects).

Through 120 Months, the percentage of subjects who experienced at least one adverse event is
similar in the 2-level Prestige LP™ group (98.6%) and the 2-level ACDF control group (95.2%).
Some of the more commonly reported clinically relevant adverse events through all available
follow-up were neck and/or arm pain (in 74.2% of 2-level Prestige LP™ subjects and 76.1% of
2-level ACDF control subjects), neurological adverse events (in 56.5% of 2-level Prestige LP™
subjects and 59.6% of 2-level ACDF control subjects), cervical study surgery spinal events (in

20.6% of 2-level Prestige LP™ subjects and 12.2% of 2-level ACDF control subjects), cervical
Heterotopic Ossification (in 16.7% of 2-level Prestige LP™ subjects and 16.0% of 2-level ACDF
control subjects), dysphagia/dysphonia (in 8.6% of 2-level Prestige LP™ subjects and 12.8% of
2-level ACDF control subjects), non-infectious wound adverse events (in 8.6% of 2-level
Prestige LP™ subjects and 6.9% of 2-level ACDF control subjects), and implant adverse events
(in 7.7% of 2-level Prestige LP™ subjects and 9.0% of 2-level ACDF control subjects).

Medtronic Page 66 of 103

# of Patients Reporting & Total adverse events

(≤ 24 Months)

INV

INV

INV

INV

INV

INV

INV

TOTAL ADVERSE EVENTS

55

38

166

222

116

119

229

267

246

241

373

397

300

319

195 (93.3%)

1485

173 (92.0%)

1603

CANCER 0 0 0 0 0 1 0 0 0 0 0 1 0 1

0 (0.0%)

0

3 (1.6%)

3

CARDIAC DISORDERS

2 3 2 0 3 0 1 1 8 3 8 9 4 3 18 (8.6%)

28

17 (9.0%)

19

DEATH 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 (0.0%)

0

1 (0.5%)

1

DYSPHAGIA/DYSPHONIA

1 2 5

11 2 4 1 5 0 0 4 3 1 2

14 (6.7%)

14

21 (11.2%)

27

Dysphagia

1 1 4 9 1 3 0 4 0 0 3 3 1 2 10 (4.8%)

10

20 (10.6%)

22

Dysphonia

0 1 1 2 1 1 1 1 0 0 1 0 0 0 4 (1.9%)

4

5 (2.7%)

5

GASTROINTESTINAL

5 2 13

16 0 3

12 7 16 6 38

28

17

17

43 (20.6%)

101

38 (20.2%)

79

HETROTOPIC OSSIFICATION

0 0 1 2 0 2 3 5 3 5 9 3 11 7 22 (10.5%)

27

21 (11.2%)

24

Cervical

0 0 1 2 0 2 3 4 3 3 8 2 11 2 21 (10.0%)

26

14 (7.4%)

15

Non-Cervical

0 0 0 0 0 0 0 1 0 2 1 1 0 5 1 (0.5%)

1

8 (4.3%)

9

IMPLANT EVENTS

4 0 2 2 1 2 0

2

3

2 0 4 5 0

13 (6.2%)

15

10 (5.3%)

12

Breakage

1 0 0 1 0 0 0 1 0 0 0 0 0 0 1 (0.5%)

1

2 (1.1%)

2

Displacement

1 0 0 0 1 0 0 0 1 0 0 1 3 0 6 (2.9%)

6

1 (0.5%) 1 Displacement -Subsidence

0 0 0 0 0 2 0 0 2 2 0 2 1 0 2 (1.0%)

3

6 (3.2%)

6

Loosening

0 0 0 1 0 0 0 1 0 0 0 1 0 0 0 (0.0%)

0

3 (1.6%)

3

Malpositioning

2 0 1 0 0 0 0 0 0 0 0 0 0 0 3 (1.4%)

3

0 (0.0%)

0

Other

0 0 1 0 0 0 0 0 0 0 0 0 1 0 2 (1.0%)

2

0 (0.0%)

0

INFECTION*

0 1 5 7 3 3 3 7 8 3 20

11 9 9

36 (17.2%)

48

32 (17.0%)

41

NECK AND/OR ARM PAIN

13 2 38

53

36

28

60

56

44

50

52

59

53

46

127 (60.8%)

296

115 (61.2%)

294

Neck Pain (Cervical)

6 1 16

23

13

14

25

19

17

22

25

21

22

23

83 (39.7%)

124

80 (42.6%)

123

Neck Pain (Non-Cervical)

0 0 0 0 2 1 2 1 1 1 0 0 1 0 6 (2.9%)

6

3 (1.6%)

3

Arm Pain (Cervical

7 1 21

27

15

10

25

22

16

19

19

27

22

16

77 (36.8%)

125

77 (41.0%)

122

Arm Pain (Non-Cervical)

0 0 1 3 6 3 8

14

10 8 8

11 8 7

30 (14.4%)

41

33 (17.6%)

46

NEUROLOGICAL

7 8 23

25

21

23

45

41

39

22

33

45

33

28

90 (43.1%)

201

86 (45.7%)

192

Carpel Tunnel Syndrome

1 0 2 2 2 0 5 2 2 1 0 6 2 4 13 (6.2%)

14

14 (7.4%)

15

Gait Disturbance

0 0 0 1 0 1 0 1 1 0 1 1 0 1 2 (1.0%)

2

5 (2.7%)

5

Lower Extremity-Motor

0 3 0 3 0 1 0 2 2 0 1 3 1 1 4 (1.9%)

4

10 (5.3%)

11

Lower Extremity-Sensory

0 0 2 3 2 2 2 5 3 5 3 8 2 5 13 (6.2%)

14

21 (11.2%)

28

Non-Specific or Other

1 3 3 0 3 2 12

11 7 6 6 4 5 4

31 (14.8%)

37

20 (10.6%)

30

Spinal Cord Disturbance

0 0 0 0 0 1 1 0 0 0 0 1 0 0 1 (0.5%)

1

2 (1.1%)

2

Upper Extremity- Motor

0 1 2 0 3 4 2 7 3 4 4 1 4 1 15 (7.2%)

18

13 (6.9%)

18

Upper Extremity- Sensory

5 3 14

16

10

11

23

13

20 6 17

19

19

12

60 (28.7%)

108

51 (27.1%)

80

Upper and Lower Extremity-Motor

0 0 0 0 0 1 0 0 1 0 1 2 0 0 2 (1.0%)

2

3 (1.6%)

3

Upper and Lower Extremity-Sensory

0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 (0.5%)

1

0 (0.0%)

0

NON-UNION

0 0 0 1 0 1 0 7 0 6 0 2 0 1 0 (0.0%)

0

18 (9.6%)

18

OTHER 8 6

27

24

13 9 20

27

34

22

52

70

42

57

98 (46.9%)

196

87 (46.3%)

215

OTHER PAIN**

5 6 26

36

23

21

45

40

43

58

68

78

50

61

125 (59.8%)

260

114 (60.6%)

300

RESPIRATORY

4 5 8 6 1 2 3 8 3

10

14

13

14 8 29 (13.9%)

47

34 (18.1%)

52

SPINAL EVENT

2 0 3

26 7 12

20

46

32

38

46

48

41

31

76 (36.4%)

151

82 (43.6%)

201

Cervical (Study Surgery)

2 0 0

12 0 1 2 7 9 4 9 4

13 2 29 (13.9%)

35

17 (9.0%)

30

Cervical (Non-Study Surgery)

0 0 1 9 0 3 3 9 4

12

17

15

14 9 27 (12.9%)

39

36 (19.1%)

57

Non-Cervical

0 0 2 5 7 8 15

30

19

22

20

29

14

20

39 (18.7%)

77

53 (28.2%)

114

TRAUMA 0 0 0 6 5 2 8 6 8 8

15

14 9 24

37 (17.7%)

45

39 (20.7%)

60

UROGENITAL

1 1 5 4 0 5 6 3 2 4 9 5 8

14

25 (12.0%)

31

19 (10.1%)

36

VASCULAR

1

0

0 1 0 1 1

2

0

0

3

1

1

9

5 (2.4%)

6

8 (4.3%)

14

Injury Intra-op

1 0 0 0 0 0 0 0 0 0 0 0 0 0 1 (0.5%)

1

0 (0.0%)

0

Other

0 0 0 1 0 1 1

2

0 0 3 1 1

9

4 (1.9%)

5

8 (4.3%)

14

WOUND (NON-INFECTIOUS)

2 2 8 2 1 0 1 4 3 4 2 2 2 1 15 (7.2%)

19

11 (5.9%)

15

CSF Leak

0 1 0 0 0 0 0 1 0 0 0 0 0 0 0 (0.0%)

0

2 (1.1%)

2

Dehiscence

0 0 1 0 0 0 0 0 2 1 0 0 2 0 4 (1.9%)

5

1 (0.5%)

1

Hematoma

0 0 2 0 0 0 1 0 1 0 1 0 0 0 5 (2.4%)

5

0 (0.0%)

0

Other

2 1 5 2 1 0 0 3 0 3 1 2 0 1 8 (3.8%)

9

9 (4.8%)

12

Table 33a: Adverse Events Through 24 Months

Adverse Event

Surgery Peri-Op 6 Weeks 3 Months 6 Months 12 Months 24 Months

INV Subj. (% of 209) INV Events (N) CTR Subj. (% of 188) CTR Events (N)

Medtronic Page 67 of 103

INV=2-level Prestige LP™ (N=209); CT R = 2-level ACDF control ( N=188)
* All other wound infections (non-surgical/non-study site), urinary tract infec tions, or other infecti on.
** Back and/or lower extremity (LE) pain adverse events (AEs) and Headache AE’s were classified as “Other Pain” AEs for the Prestige LP™ IDE study.

# of Patients Repor ting & Total adv erse event s

(≤ 120 Months)

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV Subj.
(% of 209)

INV

Events (N)

CTR Subj.

(% of 188)

CTR

Events (N)

TOTAL ADVERSE EVENTS

221

214

143

97

203

142

86

138

192

160

156

140

206 (98.6%)

2675

179 (95.2%)

2669

CANCER 1 1 1 0 0 4 2 3 0 2 0 0

9 (4.3%) 9 13 (6.9%)

15

CARDIAC DISORDERS

1

13 4 5 5 5 2 3 6 3 5 6

37 (17.7%)

64

34 (18.1%)

56

DEATH 0 0 1 0 0 0 1 1 0 0 0 0

2 (1.0%) 2 2 (1.1%)

2

DYSPHAGIA/DYSPHONIA

0 1 0 1 2 0 0 1 2 1 0 0 18 (8.6%)

19

24 (12.8%)

31

Dysphagia

0 1 0 1 2 0 0 1 2 1 0 0 14 (6.7%)

15

23 (12.2%)

26

Dysphonia

0 0 0 0 0 0 0 0 0 0 0 0 4 (1.9%)

4

5 (2.7%)

5

GASTROINTESTINAL

18 5 6 8 13 3 3 7 8 7 13 4 68 (32.5%)

174

50 (26.6%)

121

HETROTOPIC OSSIFICATION

3 4 1 2 5 8 3 2 4 2 6 3 40 (19.1%)

51

39 (20.7%)

46

Cervical

3 3 1 0 5 6 0 2 4 2 5 3 35 (16.7%)

44

30 (16.0%)

31

Non-Cervical

0 1 0 2 0 2 3 0 0 0 1 0 7 (3.3%)

7

13 (6.9%)

15

IMPLANT EVENTS

2 1 0 0 1 5 0 0 1 1 1 0 16 (7.7%)

20

17 (9.0%)

19

Breakage

1 1 0 0 0 1 0 0 0 0 0 0 2 (1.0%)

2

4 (2.1%)

4

Displacement

1 0 0 0 0 0 0 0 0 0 0 0 7 (3.3%)

7

1 (0.5%)

1

Displacement -Subsidence

0 0 0 0 1 0 0 0 0 0 0 0 3 (1.4%)

4

6 (3.2%)

6

Loosening

0 0 0 0 0 3 0 0 1 0 0 0 1 (0.5%)

1

6 (3.2%) 6 Malpositioning

0 0 0 0 0 0 0 0 0 0 0 0 3 (1.4%)

3

0 (0.0%)

0

Other

0 0 0 0 0 1 0 0 0 1 1 0 3 (1.4%)

3

2 (1.1%)

2

INFECTION*

5 5 2 3 5 4 1 1 3 7 5 4 45 (21.5%)

73

47 (25.0%)

80

NECK AND/OR ARM PAIN

40

34

16

13

41

26

10

22

21

28

21

23

155 (74.2%)

459

143 (76.1%)

462

Neck Pain (Cervical)

16

17 8 4

17

13 2 8

11

10

10 7 114(54.5%)

191

106 (56.4%)

187

Neck Pain (Non-Cervical)

1 0 1 0 4 0 0 0 1 1 2 0 14 (6.7%)

15

4 (2.1%)

4

Arm Pain (Cervical

14 7 4 5 14 7 1 5 7 7 7 6 98 (46.9%)

177

94 (50.0%)

164

Arm Pain (Non-Cervical)

9

10 3 4 6 6 7 9 2 10 2 10

52 (24.9%)

76

55 (29.3%)

107

NEUROLOGICAL

24

20

10

10

17

13 8 6

37

26

24

22

118 (56.5%)

352

112 (59.6%)

308

Carpel Tunnel Syndrome

0 2 3 0 1 0 2 2 1 0 2 1 20 (9.6%)

26

20 (10.6%)

21

Gait Disturbance

0 0 0 0 1 1 0 0 0 0 0 2 3 (1.4%)

3

7 (3.7%) 8 Lower Extremity-Motor

2 0 1 0 2 2 0 0 0 1 0 2 12 (5.7%)

14

13 (6.9%)

17

Lower Extremity-Sensory

5 4 1 1 0 1 1 0 6 5 1 2 24 (11.5%)

36

26 (13.8%)

43

Non-Specific or Other

2 3 2 2 4 2 2 1 3 4 6 1 48 (23.0%)

60

33 (17.6%)

48

Spinal Cord Disturbance

0 0 0 0 0 1 0 0 1 0 0 1 2 (1.0%)

2

4 (2.1%)

4

Upper Extremity- Motor

0 3 1 2 1 0 0 0 6 5 5 5 23 (11.0%)

31

22 (11.7%)

33

Upper Extremity- Sensory

15 8 2 5 8 6 3 3 20

11

10 8 85 (40.7%)

177

75 (39.9%)

130

Upper and Lower Extremity-Motor

0 0 0 0 0 0 0 0 0 0 0 0 2 (1.0%)

2

4 (2.1%)

4

Upper and Lower Extremity-Sensory

0 0 0 0 0 0 0 0 0 0 0 0 1 (0.5%)

1

0 (0.0%)

0

NON-UNION

1 4 0 0 0 0 0 0 0 1 0 0 1 (0.5%)

1

22 (11.7%)

23

OTHER

26

37

18

13

30

17

13

19

15

14

13

17

123 (58.9%)

338

115 (61.2%)

364

OTHER PAIN**

50

37

27

18

41

21

22

27

40

21

24

21

160 (76.6%)

502

138 (73.4%)

479

RESPIRATORY

4 5 10 4 3 2 3 3 5 8 3 2 44 (21.1%)

80

53 (28.2%)

85

SPINAL EVENT

24

23

24

11

24

26 9 28

34

32

26

27

113 (54.1%)

315

112 (59.6%)

369

Cervical (Study Surgery)

8 1 1 0 7 3 0 6 3 1 2 0 43 (20.6%)

57

23 (12.2%)

43

Cervical (Non-Study Surgery)

5

19 2 6 9 21 3 14 9 18 7 23

51 (24.4%)

79

77 (41.0%)

163

Non-Cervical

11 3 21 5 8 2 6 8 22

13

17 4 71 (34.0%)

179

63 (33.5%)

163

TRAUMA

10

12 8 3

13 6 4

11 6 3

10 8 68 (32.5%)

101

63 (33.5%)

112

UROGENITAL

10

11

11 4 2 1 4 4 5 4 5 3 48 (23.0%)

74

34 (18.1%)

64

VASCULAR

2 0 4 1 0 1 0 0 2 0 0 0 12 (5.7%)

16

10 (5.3%)

16

Injury Intra-op

0 0 0 0 0 0 0 0 0 0 0 0 1 (0.5%)

1

0 (0.0%)

0

Other

0 0 4 1 0 1 0 0 2 0 0 0 11 (5.3%)

15

10 (5.3%)

16

WOUND (NON-INFECTIOUS)

0 1 0 1 1 0 1 0 3 0 0 0 18 (8.6%)

25

13 (6.9%)

17

CSF Leak

0 0 0 0 0 0 0 0 1 0 0 0 1 (0.5%)

1

2 (1.1%)

2

Dehiscence

0 0 0 0 0 0 0 0 0 0 0 0 4 (1.9%)

5

1 (0.5%)

1

Hematoma

0 1 0 0 1 0 0 0 0 0 0 0 7 (3.3%)

7

1 (0.5%)

1

Other

0 0 0 1 0 0 1 0 2 0 0 0 10 (4.8%)

12

10 (5.3%)

13

Table 33b: Adverse Events Through 120 Months

Adverse Event

36 Months 48 Months 60 Months 72 Mon ths 84 Months 120 Months

Medtronic Page 68 of 103

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
* All other wound infections (non-surgical/non-study site), urinary tract infections, or other infection.
** Back and/or lower extremity (LE) pain adverse events (AEs) and He ad ache AE’s were classified as “Other Pain” AEs fo r the Prestige LP™ IDE study.

Adverse Event

Definition

Cancer

A malignancy or malignant tumor/neoplasm

Cardiac Disorders

Any condition of the heart

Death Termination of life due t o any ca use

Dysphagia/Dysphonia

• Dysphonia

• Difficulty in speaking

Gastrointestinal

Any conditi o n pe r taining to the stomach and int e s tines

Heterotopic Ossification

the body

Implant Events

• Other

displacement, implant loosening, or implant breaking

Infection

• Any infection not listed above

Neck and/or Arm Pain

Neurological

radiating, continuin g, exten din g, or spr eading t o an ad jace nt anat omy

Non-Union

Failure of the vertebral bodies to fuse at the treated level

Table 34: Adverse Event Categories

• Dysphagia

• Heterotopic Ossification – Cervical

• Heterotopic Ossification – Non-Cervical

• Breakage

• Displacement

• Displacement –Subsidence

• Loosening

• Malpositioning

• Other Wound Infection-Non-Surgical/Non-

Study Site

• Superficial Surgical Site (Skin to Fasciae)-

Cervical

• Urinary Tract Infection

• Other Infection

• Neck Pain (Cervical)

• Neck Pain (Non-Cervical)

• Arm Pain (Cervical)

• Arm Pain (Non-Cervical)

• Difficulty in swallowing

• Event involving heter otopic ossif ication at any r egio n of the c ervic al sp ine

• Event involving heter otopic ossif ication at any r egio n of the s pine that is n ot cer vi cal or a ny other re gion of

• Breakage of a n y implant or implant compo nent

• Incomple t e or pa rtial disloc ation of the im pl ant

• Event associated with implant subsidence into the vertebral body when the reported term includes

“subsidence”

• Wear around the implant and/or loosening of the implant surface

• Poor or inap propriate pl a cement of the im pl ant

• Event that is imp lant-related, but does not meet the definit io n of ma l positioned imp la nt, implant

• Infection occurring in other surgical wound not involving the study

• Infection near the surface of the surgical incision

• Infection in any part of the urinary system

• Pain involving the ne ck r egion, which d oes not include neur ologi cal sys tems . The s ymptom s ar e such that

cervical spine etiolog y can not be rule d o ut

• Pain involving the ne ck w hich doe s no t incl ude nec k neur ologi cal sym ptom s. I nforma tion is ava ilabl e at t he

reported event time to r eas onably r ule o ut cer vical spi ne eti ology

• Pain involving the arm, which does not i nclude neurolo gical s ympt oms. These symptom s ar e such tha t a

cervical spine etiolog y can not be rule d o ut

• Pain involving the ar m w hich do es not i nclude neck ne urolog ical s ympt oms . I nformation is availa ble at t he

reported event time t o reas onably r ule o ut cer vical spi ne et iology

• Carpal Tunnel Syndrome

• Gait Disturbance

• Lower Extremity-Motor

• Lower Extremity-Sensory

• Non-Specific or other

• Spinal Cord Disturbance

• Upper Extremity – Motor

• Upper Extremity – Sensory

• Upper & Lower Extremity-Motor

• Upper & Lower Extremity-Sensory

• Event that is descr ibes a s Car pal Tunne l Syndrom e or CTS

• Neurological conditi on i n whic h the ga it is aff ected

• Event that involves a feel ing or awa renes s of condition wi thin th e bo dy res ultin g f rom s timula tion of m otor

neurons that induce m ovements , as ner v es or m uscle s. S uch movem ents w ould a ffe ct any par t of the lower
extremity including the hip, th igh, ca lf , foot, or toes an d may be muscu lar in natu re

• Event that inv olves a fee ling or awa renes s of condition wi thin th e bo dy res ultin g f rom s timula tion of

sensory receptors. Such sensation woul d af fect any part of the low er e xtrem ity inc luding th e hip, t hig h,
calf, foot, or toes and m ay be ra diat ing, c ontin uing, extending, or spr eading t o an adj acent a natomy

• Neurological event not as sociat ed wit h a ny othe r neur ologic al categ ori es or a re neur ological in nat ure but

not specific enough to f it int o othe r subc ategor ies

• Condition in which t her e is a dis ruption or dis turba nce to t he spina l cor d

• Event that involves stimula tion of t he motor neurons that induce moveme nts , as ner ves or mus cles. S uch

events would affect any par t of the up pe r extr emi ty includi ng the s houlde r, br ach ium, elbow , f orear m, ha nd,
and fingers and may be muscul ar in na tu re

• Event that involves a feel ing or awa renes s of condition wi thin th e bo dy res ultin g f rom s timula tion of

sensory receptors. Such sensation would af fect any part of the upper extr emity inc luding the sh oulder,
brachium, elbow, forearm, hand, and f inge rs a nd may be r adiati ng, co ntin uing, e xtendi ng, or spre ading t o
an adjacent anatomy

• Event that involves a feel ing or awa renes s of condition wi thin th e bo dy res ultin g f rom s timula tion of m otor

neurons that induce m ovements , as ner v es or muscle s. S uch events would af fe ct any par t of the u pper or
lower extremity and m ay be m uscula r in nature

• Event that involves a feel ing or awa renes s of condition wi thin th e bo dy res ultin g f rom s timula tion of

sensory receptors. Such s ensation w ould aff ect any par t of the upper or lower ext rem ity and ma y be

Medtronic Page 69 of 103

Adverse Event

Definition

Other

Event not associated with any other categories (e.g., weight loss , tinni tus, s ubsta nce abus e, ins omnia )

Other Pain

• Other

(e.g., earache, fibromyalgia, non-car diac chest pain, sore throat, arthritis)

Respiratory

Ailments or symptom s ass ociated w ith r espir ation or t he res pirat ory sys tem

Spinal Event

• Non-Cervical

radiologic findings

Trauma

Physical injury caused by a physical force or trau matic event (e.g. motor veh icle accident, fall, etc. )

Urogenital

Any conditi o n of, relating t o, af f ecting, trea ting, or being t he or g a ns or functio ns of e xcretion and
reproduction

Vascular

• Disorder or condition in which the vascu lar s ystem is aff ected

Wound (Non-Infectious)

• Other

tissue, incisional ed emas, scratches to skin sur face)

• Back pain

• Headache

• Lower Extremity Pain

• Cervical Study Surgery

• Cervical Non-Study Surgery

• Injury (intra-operative)

• Other

• CSF Leak

• Dehiscence

• Hematoma

• Pain (including sti ff ness, s tra in, tightnes s) in an ar ea that i s not of t he ce rvical spi ne region, occ urri ng in the

back (e.g., low back pain, thoracic bac k pai n, bac k pain)

• Pain occurring in the head ( e.g., headache, migraine headache, head pain)

• Pain occurring in the low er extr emi ty and us ing the term “pain” ( e.g., le g pai n, k nee pain, calf pain, f oot

pain)

• Pain occurring in parts of the body that are not classified as headache, back pain, or lower extremity pain

• Event involving cer vica l spine diagn ose s at the study tr eatmen t leve l; us uall y conf irm ed via r adiologi c

findings

• Event involving cer vica l spine diagn ose s at one or mor e cervical spine level(s ), with the exception of the

treated level; usually c onfi rme d via radi ologic f in dings

• Event involving dia gnos es at one or m ore spine level s o ther than c er vical s pine; usually co nfi rme d via

• Injury to a vascula r st ructur e that is susta ined dur ing the c ours e of the operat ive p roc edure; i nitial st udy

surgery only

• Compromise or tear of the dura mater resulting in leakage of cerebral spinal fluid, excluding

infection. Fluid is clear and free of microorganisms

• A bursting open or separation of a wound without the presence of microorganisms

• Swelling or mass of bloo d ( us u ally clotte d) confined to an organ, tissue , or s pace and cause d b y a

break in a blood vessel. Wound is not limited to a specific anatomic region and there is an absence of
microorganisms

• Wound condition in which there is an absence of infection or oth er fea tur e ( e.g ., w o un d o ozi n g, scar

Bayesian analyses were conducted to compare adverse events in main categories and
subcategories using non-informative priors. The results up to 24-month visit are presented in
Table 35a with 95% Bayesian Credible Intervals (BCI) for the difference in adverse event rates
(2-level Prestige LP™ – 2-level ACDF). The long-term data were presented in Table 35b with
posterior mean and the 95% BCI for the log hazard ratio (LHR). Although there was no
adjustment for multiplicity, BCIs that exclude zero indicate statistical differences in the adverse
event rates when comparing the 2-level Prestige LP™ group and the 2-level ACDF control
group.

Medtronic Page 70 of 103

Posterior Mean and 95%

between INV and CTR

INV

CTR

INV

CTR

INV – CTR

Total Subjects

Adverse Events

Cancer

0 (0.0%)

3 (1.6%)

0.5% (0.0%, 1.4%)

2.1% (0.4%, 4.2%)

-1.6% (-4.0%, 0.4%)

Cardiac Disorders

18 (8.6%)

17 (9.0%)

9.0% (5.3%, 12.9%)

9.5% (5.5%, 13.7%)

-0.5% (-6.2%, 5.2%)

Death

0 (0.0%)

1 (0.5%)

0.5% (0.0%, 1.4%)

1.1% (0.0%, 2.5%)

-0.6% (-2.5%, 1.1 %)

Dysphagia /
Dysphonia

Gastrointestinal

43 (20.6%)

38 (20.2%)

20.9% (15.5%, 26.4% )

20.5% (14.9%, 26.3%)

0.3 % (-7.6 % , 8.2%)

Heterotopic
Ossification

Implant Events

13 (6.2%)

10 (5.3%)

6.6% (3.5%, 10.1%)

5.8% (2.7%, 9.2%)

0.8% (-3.9%, 5.6%)

Infection

36 (17.2%)

32 (17.0%)

17.5% (12.6%, 22.8%)

17.4% (12.1%, 22.8%)

0.2% (-7.3%, 7.6%)

Neck and / or Arm
Pain

Neurological

90 (43.1%)

86 (45.7%)

43.1% (36.5%, 49.8%)

45.8% (38.7%, 52.8%)

-2.7% (-12.4, 7.0%)

Non-Union

0 (0.0%)

18 (9.6%)

0.5% (0.0%, 1.4%)

10.0% (5.9%, 14.3%)

-9.5% (-14.0%, -5.4%)**

Other

98 (46.9%)

87 (46.3%)

46.9% (40.2%, 53.6%)

46.3% (39.3%, 53.5%)

0.6% (-9.1%, 10.4%)

Other Pain

125 (59.8%)

114 (60.6%)

59.7% (53.1%, 66.2%)

60.5% (53.6%, 67.4%)

-0.8% (-10.3%, 8.8%)

Respiratory

29 (13.9%)

34 (18.1%)

14.2% (9.7%, 19.0%)

18.4% (13.0%, 24.0%)

-4.2% (-11.5%, 3.0%)

Spinal Event

76 (36.4%)

82 (43.6%)

36.5% (30.0%, 43.0%)

43.7% (36.7%, 50.7%)

-7.2% (-16.7%, 2.4%)

Trauma

37 (17.7%)

39 (20.7%)

18.0% (13.0%, 23.3%)

21.1% (15.4%, 26.9%)

-3.0% (-10.8%, 4.7%)

Urogenital

25 (12.0%)

19 (10.1%)

12.3% (8.1%, 16.8%)

10.5% (6.4%, 15.0%)

1.8% (-4.4%, 8.0%)

Vascular

5 (2.4%)

8 (4.3%)

2.8% (0.9%, 5.1%)

4.7% (2.0%, 7.8%)

-1.9% (-5.7%, 1.9 %)

Wound
(Non-Infectious)

INV (N=209)

CTR (N=188)

Posterior M ean of log

Events

Subjects
rate %))

Events

Subjects
rate %))

Total Subjects Exper iencin g Adver se E vents

2675

206 (98.6%)

2669

179 (95.2%)

0.02 (-0.1 8, 0.23)

Cancer 9 9 (4.3%)

15

13 (6.9%)

-0.61 (-1.49 , 0.26)

Cardiac Disorders

64

37 (17.7%)

56

34 (18.1%)

-0.12 (-0.58 , 0.36)

Death 2 2 (1.0%)

2

2 (1.1%)

-0.22 (-2.49 , 2.04)

Dysphagia / Dysphonia

19

18 (8.6%)

31

24 (12.8%)

-0.46 (-1.07 , 0.17)

Gastrointestinal

174

68 (32.5%)

121

50 (26.6%)

0.16 (-0.2 1, 0.52)

Heterotopic Ossification

51

40 (19.1%)

46

39 (20.7%)

-0.19 (-0.63 , 0.26)

Implant Events

20

16 (7.7%)

19

17 (9.0%)

-0.23 (-0.92 , 0.46)

Infection

73

45 (21.5%)

80

47 (25.0%)

-0.22 (-0.63 , 0.19)

Neck and / or Arm Pain

459

155 (74.2%)

462

143 (76.1%)

-0.13 (-0.36 , 0.10)

Neurological

352

118 (56.5%)

308

112 (59.6%)

-0.12 (-0.38 , 0.14)

Non-Union

1

1 (0.5%)

23

22 (11.7%)

-3.83 (-6.38, -1.69)**

Other

338

123 (58.9%)

364

115 (61.2%)

-0.07 (-0.32 , 0.19)

Other Pain

502

160 (76.6%)

479

138 (73.4%)

-0.03 (-0.26 , 0.20)

Respiratory

80

44 (21.1%)

85

53 (28.2%)

-0.40 (-0.80 , 0.00)

Spinal Event

315

113 (54.1%)

369

112 (59.6%)

-0.28 (-0.54, -0.02)**

Trauma

101

68 (32.5%)

112

63 (33.5%)

-0.13 (-0.47 , 0.21)

Urogenital

74

48 (23.0%)

64

34 (18.1%)

0.17 (-0.2 8, 0.61)

Vascular

16

12 (5.7%)

16

10 (5.3%)

0.01 (-0.8 6, 0.86)

Wound (Non-Infectious)

25

18 (8.6%)

17

13 (6.9%)

0.21 (-0.5 2, 0.92)

Table 35a: Bayesian Comparison of Posterior Probabilities of Adverse Events in

Main Categories at 24 Month Interval

Adverse Event

Subjects Experiencing Adverse

Experiencing

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
* BCI = Bayesian HPD Credible Interval
**BCI excluding 0

Events (%)

195 (93.3%) 173 (92.0%) 92.9 (89.4%, 96.2%) 91.6% (87.5%, 95.3%) 1.3% (-3.9%, 6.6%)

14 (6.7%) 21 (11.2%) 7.1% (3.8%, 10.6%) 11.6% (7.2%, 16.2%) -4.5% (-10.2%, 1.2%)

22 (10.5%) 21 (11.2%) 10.9% (6.8%, 15.1%) 11.6% (7.2%, 16.2%) -0.7% (-6.9%, 5.5%)

127 (60.8%) 115 (61.2%) 60.7% (54.0%, 67.2%) 61.0% (54.1% , 67.9%) -0.4% (-9.9%, 9.2%)

15 (7.2%) 11 (5.9%) 7.6% (4.2%, 11.2%) 6.3% (3.1%, 9.8%) 1.3% (-3.8%, 6.2%)

Posterior Mean and 95% HPD of Adverse Event

Rate

BCI* of the Difference of

Adverse Event Rate

Table 35b: Bayesian Comparison of Posterior Probabilities of Adverse Events in

Main Categories at 120 Month Interval

(n (cumulative

INV=2-level Prestige LP™ (N=209); CT R = 2-level ACDF control ( N=188)

* BCI = Bayesian HPD Credible Interval

**BCI excluding 0

(n (cumulative

Hazard Ratio (95% BCI*)

Medtronic Page 71 of 103

Deaths:
Prior to 24 months, one death occurred in the control group and none in the investigational
group. By 120 months, there were two deaths in the investigational group and one death in the
control group. The deaths were evaluated by the CAC, and based upon available information
were determined to be unrelated to the study treatments.

Subsequent Surgical Interventions at the Index Level:
Some adverse events resulted in surgical intervention at one or both of the index levels,
subsequent to the initial surgery. Subsequent surgical interventions at the index level(s) were
classified as revisions, supplemental fixations, non-elective removals, elective removals,
reoperations or other surgical procedures. Per the study protocol, revisions, supplemental
fixations, and non-elective removals were considered subsequent surgery failures, whereas
reoperations, elective removals, and other surgical procedures were not considered subsequent
surgery failures. Overall, there were 11 subsequent surgical interventions at the index level(s) in
9 (4.3%) 2-level Prestige LP™ subjects and 33 subsequent surgical interventions at the index
level(s) in 27 (14.4%) 2-level ACDF control subjects.

The timecourse of the subsequent surgical interventions through all available follow-up is summarized in Table 36a and 36b.

Table 36a and 36b also presents the Bayesian statistical comparison of subsequent surgeries at
the index level(s) through 24 and 120 months between the 2-level Prestige LP™ and 2-level
ACDF control treatment groups. Through 24 months, there were a greater number of subjects
who underwent subsequent surgical interventions at the index level(s) in the 2-level ACDF
control group [15 (8.0%)] compared to the 2-level Prestige LP™ group [5 (2.4%)]. Through 120
months, there were a greater number of subjects who underwent subsequent surgical
Interventions at the index level(s) in the 2-level ACDF control group [27 (14.4%)] compared to
the 2-level Prestige LP™ group [9 (4.3%)]. The significance was achieved since the BCI for the
difference of event rates (for the 24-month data) or the log hazard ratio (for the 120-month data)
excludes 0, and the rates were statistically different without adjusting for multiplicity.

Medtronic Page 72 of 103

Posterior Mean and

Surgery Rate

# of Patients Reporting & Total

(≤ 24 Months)

Revision

1

0.5%

(0.0%, 1.4%)

1.1%

(0.0%, 2.5%)

-0.6%

(-2.5%, 1.1%)

0

(0.0%)

1

(0.5%)

Supplementa l fixation

2

0.9%

(0.0%, 2.3%)

2.1%

(0.4%, 4.2%)

-1.2%

(-3.7%, 1.2%)

1

(0.5%)

3

(1.6%)

Non-elective removal

3

1.9%

(0.3%, 3.7%)

3.7%

(1.3%, 6.4%)

-1.8%

(-5.1%, 1.4%)

3

(1.4%)

6

(3.2%)

Elective removal

4

0.5%

(0.0%, 1.4%)

1.6%

(0.2%, 3.3%)

-1.1%

(-3.3%, 0.8%)

0

(0.0%)

2

(1.1%)

Reoperation5

1.4%

(0.1%, 3.0%)

2.6%

(0.7%, 4.9%)

-1.2%

(-4.1%, 1.5%)

2

(1.0%)

4

(2.1%)

TOTAL

2.8%

(0.8%, 5.1%)

8.4%

(4.7%, 12.5%)

-5.6%

(-10.2%, -1.1%)

5

(2.4%)

15

(8.0%)

External bone growth
stimulator

5

(2.7%)

Table 36a: Subsequent Surgical Interventions at the Index Level(s) Through 24-Month Follow-up

Posterio r Mean

Surgery Peri-Op 6 Weeks 3 Months 6 Months 12 Months 24 Months

Type

INV

0 0 0 0 0 1 0 0 0 0 0 0 0 0

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

95% HPD of Subsequent

INV CTR

CTR

and 95% BCI*
of Differen ce o f

Surgery Rate

INV and CTR

Subsequent

between

INV

Subj.

(% of 209)

Events

INV

Events

(N)

0

CTR
Subj.

(% of 188)

CTR

Events

(N)

1

0 0 0 0 0 0 0 0 0 1 1 2 0 0

0 0 0 0 1 0 0 1 0 2 1 2 1 1

0 0 0 0 0 0 0 1 0 0 0 0 0 1

0 0 0 0 0 0 0 2 1 0 1 2 0 1

0 0 0 0 1 1 0 4 1 3 3 6 1 3

6

NA 0 NA 0 NA 0 NA 0 NA 4 NA 1 NA 0 NANA NANA NANA NANAta NA

1

3

0

2

6

3

6

2

5

17

5

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

* BCI = Bayesian HPD Credible Interval

1

A procedure that adjusts or i n a ny way modifies e i t h er o n e or both of the original implant configurations (e.g., adjusting position of the original configuration, removal with replacement with the same type

of study implant).

2

A procedure at the involved level(s) in which addit ional spinal devices not approved as part of the protocol are placed. This categorization of Supplemental Fixations does not include supplemental

therapies (i.e. external bone growth stimulators).

3 Any procedure that removes the device as the result of an adverse event.
4 A procedure that removes the device at the dis c retion of the in ve stigator and/or the pati e nt an d i s not the result of an adverse event.
5 A procedure th a t in volves any s ur gi c al procedure at the involve d le ve l ( s ) th a t d oe s n ot remove, modi fy, or add any components and that is not considered a Removal. Revision, or Supplemental Fixation
6 There were a total of 5 external bone growth stimulators used in the 2-level ACDF control group. While the use of external bone growth stimulators were not considered a secondary surgery, these subjects

were considered failures in the original primary endpoint analysis. However, a sensitivity analysis was provided to FDA in which they were not considered failures.

Medtronic Page 73 of 103

Revision

1

0

(0.0%)

2

(1.1%)

-798.11

(-1956.24, 0.60)

Supplementa l fixation

2

2

(1.0%)

8

(4.3%)

-1.81

(-3.58, -0.17)

Non-elective removal

3

6

(2.9%)

7

(3.7%)

-0.35

(-1.48, 0.80)

Elective removal

4

0

(0.0%)

9

(4.8%)

-802.74

(-1959.04, -1.53)

Reoperation5

3

(1.4%)

5

(2.7%)

-0.78

(-2.32, 0.75)

TOTAL

9

(4.3%)

27

(14.4%)

-1.39

(-2.15, -0.61)

External bone growth
stimulator

5

(2.7%)

-799.85

(-1961.63, -1.23)

Table 36b: Subsequent Surgical Interventions at the Index Level(s) Through 120-Month Follow-up

Type

36 Months

INV

CTR

48 Months

INV

CTR

60 Months

INV

CTR

72 Months

INV

CTR

84 Months

INV

CTR

120 Months

INV

0 0 0 0 0 0 0 0 0 0 0 0

0 1 0 1 0 1 0 0 0 1 0 0

2 1 0 0 1 0 0 0 0 0 0 0

0 0 0 1 0 1 0 3 0 1 0 0

0 0 0 1 0 0 1 1 0 0 0 0

2 2 0 3 1 2 1 4 0 2 0 0

6

NA 0 NA 0 NA 0 NA 0 NA 0 NA 0 NA NA

# of Patients Reporting & Total Events

(≤ 120 Months)

INV

Events

(N)

CTR

INV Subj.

(% of 209)

0

2

6

0

3

11

CTR Subj.

(% of 188)

CTR

Events

Posterior Mean of log

Hazard Ratio

(95% HPD)

(N)

2

8

7

9

7

33

5

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACD F co ntrol (N=188)

* BCI = Bayesian HPD Credible Interval

1

A procedure that adjusts or i n a ny way modifies e i t h er o n e or both of the or iginal implan t configurations (e.g., adjusting position of the original configuration, removal with replacement with the same type

of study implant).

2

A procedure at the involved level(s) in which additional spinal devices not approved as part of the protocol are placed. This categorization of Supplemental Fixations does not include supplemental

therapies (i.e. External bone growth stimulators).

3 Any procedure that removes the device as the result of an adverse event.
4 A procedure that removes the device at the discretion of th e in ve stigator and/or the patient and is not the r es ult of an adverse event.
5 A procedure th a t in volves any s ur gi c al procedure at the involve d le ve l ( s ) th a t d oe s n ot remove, modi fy, or add any components and that is not considered a Remo va l. Revision, or Supplemental Fixation
6 There were a total of 5 external bone growth stimulators used in the 2-level ACDF control group through all follow-ups. While the use of external bone growth stimulators were not considered a secondary

surgery, these subjects were considered failures in the original primary endpoint analysis. However, a sensitivity analysis was provided to FDA in which they were not considered failures.

Medtronic Page 74 of 103

Surgical

Type

Procedure

Procedure

Adverse Event Type

Days From

Procedure

Device(s)

Supplemental

C4, C5, C6 laminectomy an d C7 partial

C4-C5 &

Cervical spondylotic myelopathy;

553

No

Supplemental

C5-C6 Foraminotomies and posterior

C5-C6 &

Parascapular pain an d num b n ess in

backwards

3453

No

Non-Elective

Explant both Prestige LP™ (C5-C6 & C6-

tissue debridement

C5-C6 &

Right arm radicu la r pa in ; p os i tive

40

Yes, both

Non-Elective

Explant both Prestige LP™ (C5-C6 & C6-

anterior cervical fusion

C5-C6 &

Post-surgical cervical kyphosis;

486

Yes, both

Non-Elective

Explant both Prestige LP™ (C5-C6 and

C5-C6 &

C4-C5 disc bulge/protrusion; C4-

and C6-C7 posterior osteophytes

624

Yes, both

Non-Elective

Explant one level Prest i ge LP ™ (C 6-C7);

stabilization by plate

C5-C6 &

Failed cervical disc arthroplasty

cord compression

929

Yes, one

Non-Elective

Explant both Prestige LP™ (C5-C6 and

cervical titanium plate

C5-C6 &

Foraminal stenosis secondary to

994

Yes, both

Non-Elective

Explant both Prestige LP™ (C4-C5 and

C4-C5 &

Progressive subsidence of C4-C5

intractable cervicogenic headache

1641

Yes, both

Reoperation

C5-C6 and C6-C7 Microforaminotomy and

hemilaminectomy

C5-C6 &

C5-C6 and C6-C7 foraminal

222

No

Reoperation

Rhizotom y C2-C3, C6-C7, and C7-T1

C5-C6 &

Increased ne ck pain

529

No

Table 37 provides detailed information on each 2-level Prestige LP™ subsequent surgical
intervention at the index level(s). Similarly, Table 38 provides detailed information on each 2­level ACDF control group subsequent surgical intervention at the index level(s).

Table 37: Detailed Information on 2-level Prestige LP™ Subsequent Surgical

Interventions at the Index Levels – Proc ed u re Deta il s

Intervention

Fixation

Fixation

Removal

Removal

Removal

Removal

Removal

Type

laminectomy; C3-C4, C4-C5, C5-C6, and

C6-C7 arthrodesis; pos ter i or cer v ic al spinal

C7); C5-C6 and C6-C7 partial corp ectomy
and fusion with allograft bone; C5-C6 and

C6-C7 revision of foraminotomy and scar

C7); C4-C5, C5 -C6, and C6-C7 anterior

decompression and discectomy; C4-C7

C6-C7); C5-C6 and C6-C7 anterio r cervical

discectomy and fusi on; C4-C5 artificial

microdiscectom y, bil ateral anterior

decompression at C5-C6 and C6-C7;

anterior fusion using PEEK spacer and

demineralized bone matrix plus anterior

instrumentation

fusion surgery

disc (Prestige ST)

iliac crest allograft arthrodesis and

C6-C7); redo anterior cervical

foraminotomies an d ce ntral canal

Level(s)

C5-C6

C6-C7

C6-C7

C6-C7

C6-C7

C6-C7

C6-C7

cervical radiculopathy

arms when bending neck

foraminal c ompression test

sagittal imbalance

C5 left paracentral foraminal

narrowing; C5-C6 and C6-C7 mid-

foraminal encroac hment; C6-C7

right foraminal narrowing; C5-C6

with cervical stenosis and C6-C7

loosening of h ar dware;

Exacerbation of res idual symptoms

secondary to motor vehicle

accident

Index

Removed?

levels

levels

levels

level

levels

Removal

Medtronic Page 75 of 103

C5-C6); C5 cor pectomy; C4 to C6 anterior
fusion; revision bilateral C4 -C5 and C5-C6

decompressive foraminotomy; C6-C7

anterior cervical discectomy and fusio n

using PEEK interbody cage and local

autograft bone; combined C4 to C7

instrumen ted posterol ateral fusion

C5, C6, and C7 partial right

left/right

C5-C6

C6-C7

C6-C7

and C5-C6 artificial discs, recurrent

C4-C5 and C5-C6 bilateral

foraminal stenosis, advanced C6-

C7 cervical spondyl itic

degenerative change wi t h bilateral

C6-C7 foraminal stenosis,

intractable neck pain and bilateral

upper extremity radiculopathy,

stenosis on the right

levels

Reoperation

C4-C5 explant of Prestige™ ST artificial

conventional sc rews

C5-C6 &

C4-C5 central c anal narrow i ng due

2061

No

Surgical

Type

Procedure

Procedure

Adverse Event Type

Days From

Procedure

Device(s)

Revision

C5-C6 and C6-C7 removal o f plate and

plate and screws

C5-C6 &

C6-C7 recurrent disc herniation

37

Yes, both

Revision

C5-C6, C6-C7 anterior cervical

discectomy with fusion

C5-C6 &

C6-C7

Continued neck pain; cervical

occipital headaches

2971

No

Supplemental

C5 to C7 posterior fusion and posterior

crest bone graft

C5-C6 &

C5-C6 and C6-C7 pseudart hr osis;

257

No

Supplemental

C5-C6 and C6-C7 left laminotomy and

fusion; BMP an d local graft

C5-C6 &

C5-C6 and C6-C7 failed fusion;

319

No

Supplemental

C5-C6 bilateral foraminotomies and C5-

instrumentation

C5-C6 &

C5-C6 nonunion; cervical

429

No

Supplemental

C6-C7 and C7-T1 posterior cervical

aspirate

C5-C6 &

C6-C7 nonunion with cervical

1176

No

Supplemental

Fixation

C5-C6 posterior fusion and posterior

lateral mass screws and rods; BMP

C5-C6 &

C6-C7

C5-C6 pseudarthrosis; neck pain

1351

No

Supplemental

C3, C4, C5, C6, and C7 laminoplasty

fusion with allograft bo ne

C5-C6 &

Cervical spinal cord compression

1861

No

Supplemental

Fixation

C3 to C7 decompression and posterior

spinal fusion

C5-C6 &

C6-C7

C3-C4 osteophyte with central disc

protrusio n; c er vical pain

2497

No

Supplemental

C3-C4 Posterior bi lateral

instrumentation C3-C4

C4-C5 &

Cervical radiculopath y,

3358

Yes, both

Non-Elective

C5-C6 and C6-C7 anterior cervical

anterior instr umentation

C5-C6 &

C5-C6 and C6-C7 nonunion;

122

Yes, both

Non-Elective

C5-C6 and C6-C7 removal of anterior

with PEEK and BMP

C5-C6 &

C6-C7 nonunion

162

Yes, both

Non-Elective

C5-C6 and C6-C7 removal anterior

C7 anterior interbody fusion with PEEK

C5-C6 &

C5-C6 and C6-C7 nonunion with

223

Yes, both

disc followed by removal of anterior

cervical plate from C5 t hro ug h C 7,

exploration of cervical spinal fusion mass

C5 through C7 (solid), anterior partial

vertebral c orpectomy inf erior C5 and

superior C4, decompression of nerve roots

and resection of spurs posteriorly with

resection of scar tissu e at C4-C5, anterior

fusion, bone morphogenetic protein at C4-

C5, anterior instrumentation with cervical

plate at C4-5-6-7 with rescue screws and

C6-C7

to spurring behind the artificia l dis c

replacement; cord compression

Table 38: Detailed Information on 2-Level ACDF Control Group Subsequent Surgical

Interventions at the Index Level(s)

Intervention

Fixation

Fixation

screws; C6-C7 allograft removal; C6-C7

replacement of C6-C 7 a ll ograft; new

lateral mas s instrumentation; left iliac

foraminot omy; C5 to C7 post er ior

Type

Level(s)

C6-C7

C6-C7

C6-C7

Index

after traumatic injury

intractable neck pai n

left cervical radiculo pa thy

Removed?

levels

Fixation

Fixation

Fixation

Fixation

Removal

Removal

Removal

C7 posterior fusion with autograft and

laminotomy and foraminotomy; C6-C7

cervical wiring; posterior fusion using

collagen sponge and iliac crest graft

and C3, C4, C5, C6, and C7 poster ior

foraminotom ies; C4-C5 foraminotomy

left side; arthrodesis C3-C4, C4-C5;

removal of interbody grafts; C5, C6, a nd

C7 partial vertebral corpectomies;
anterior interbody arthrodesis with

PEEK graft with Hydrosorb and BMP,

instrumentation and interbody grafts;

C5-C6 and C6-C7 decompres sion of

spinal cord nerve root bilaterally; C5-C6

and C6-C7 anterior interbody arthrodesis

cervical ins t rumentation and remova l of

interbody grafts; C5, C6, and C7 partial
vertebral corpectomies; C5-C6 and C6-

C6-C7

C6-C7

C6-C7

C5-C6

C6-C7

C6-C7

C6-C7

spondylosis

radiculopathy

spondylosis, kyphosis; failed back

surgical syndrome

biomechanical cer vi ca l pa in ; upper

extremity radiculopathy

loosened hardware

levels

levels

levels

levels

Medtronic Page 76 of 103

and BMP; anteri or instrumentati on

Non-Elective

C5-C6 hardware removal; C5-C6

instrumentation

C4-C5 &

Cervical spondylosis; C5-C6 cord

550

Yes, one

Non-Elective

C5-C6 and C6-C7 removal of anterior

ST disc

C5-C6 &

C5-C6 nonunion; fall; C4-C5

553

Yes, both

Non-Elective

C4-C5 and C5-C6 anterior hardware

BMP; C5-C6 plate

C4-C5 &

C5-C6 nonunion; headaches

624

Yes, both

Non-Elective

Removal

C5-C6, C6-C7 removal of control device

C5-C6 &

C6-C7

Pain primaril y in the ne ck

1071

Yes, both

levels

Elective Removal

C5, C6, and C7 removal of anterior

anterior plating

C5-C6 &

Cervical spon dylosis status po st

84

Yes, both

Elective Removal

C4-C5 and C5-C6 removal of anterior

C6-C7 anterior cervical disc arthroplasty

C4-C5 &

Cervical spondylosis; C6-C7

755

Yes, both

Elective Removal

C5-C6 and C6-C7 hardware removed ;

fusion

C5-C6 &

C4-C5 disc protrusion and spinal

1285

Yes, both

Elective Removal

C5, C6, and C7 removal of anterior

C5-C6 &

C4-C5 extruded herniated di sc

accident

1739

Yes, both

Elective Removal

C4 to C6 removal of anterior cervical

disc

C4-C5 &

C3-C4 broad protrusion indenting

2044

Yes, both

Elective Removal

C4 to C6 removal of plate and screws

osteophytectomy; microforaminotomy

C4-C5 &

C6-C7 herniated nucleus pulposus;

2145

Yes, both

Elective Removal

C4-C5, C5-C6 removal of hardware; C7

allograft and instrumentati o n

C4-C5 &

C6-C7 disc herniation; intractable

2271

Yes, one

Elective Removal

C4-C5 Cervical discectomy and fusion;

instrumentation

C5-C6 &

C4-C5 high-grade stenosis

2677

Yes, both

Elective Removal

C4-C5 Removal of anterior cervical

fusion with allograft and instrumentation

C4-C5 &

Adjacent s egment degeneration C6-

repeatedly

3453

Yes, both

Reoperation

C5-C6 posterior laminofor aminotomy

C5-C6 &

C5-C6 foraminal narrowing; C5-C6

left side; cervical radiculopathy

82

No

Reoperation

C5-C6 and C7-T1 posterior cervical

and cerebrospinal fluid leak

C5-C6 &

Postopera tive cerebros pinal fluid

108

No

Reoperation

C5, C6, C7 right median branch nerve

therapeutic blocks with subsequent

C5-C6 &

C6-C7

C5-C6 graft subsidence; neck pain;

C5-C6 and C6-C7 possible

419

No

Removal

Removal

Removal

corpectomy; C5-C6 fusion with PEEK

cage and autograft; C5-C7

instrumenta ti o n; C5-C6 removal of

interbody graft; C4-C5 anterior

discectomy; C5-C6 arthrodesis with

Hydrosorb a n d BM P; C5, C6 and C7

anterior cervical plate; C4-C5 Prestige

removal; C4-C5 and C5-C6 exploration

of fusion (C4-C5 with solid fusion); C5-

C6 partial corpectomy; C5-C6 fusion;

plate; C4-C5 discectomy; C4-C5

anterior de compressio n f or aminotomy ;

C4-C5 interbody arthrodesis with

structural allograft; C4, C5, C6, and C7

cervical plate; C4-C 5 a n d C5-C6

exploration (solid bony union at these

levels); C6 and C7 partial corpect omy;

C4-C5 anterior cervical discectomy and

C5-C6

C6-C7

C5-C6

C6-C7

C5-C6

C6-C7

compression; C6-C7 ne ur al

foraminal stenosis from osteophyte

degenerative herniated disc

C5-C6 and C6-C7 anterior cervical

discectomy and inte rbody

arthrodesis; cervica l ra diculopathy

foraminal stenosis; intractable

neck, shoulder, and arm pain

cord compression

level

levels

levels

levels

levels

levels

cervical instrumentation; C4-C5

microdiscectomy

hardware; C3-C4 an terior cervical

discectomy and disc arthroplasty; C3

and C4 partial corpectomy; Prestige ST

(fusion not ed); C6-C7 anterior cervical
discectomy and fusion with bone graft;

anterior discectomy; C6-C7

foraminot omy, anterior interbody f usion,

C5-C6, C6-C7 removal of

instrumenta ti o n, a l lo gr af t and

plate; expl or ation of fusio n a t C 4-C5,

C5-C6; C6-C7 anterior cervical

discectomy, decompres sion, inter b o dy

with nerve root decompression and C7-

T1 laminoforaminotomy with nerve root

decompression

C6-C7

C5-C6

C5-C6

C5-C6

C6-C7

C5-C6

C6-C7

fragment with myelopathy and

radiculopathy; head struck

dashboard d uring a motor ve h i cle

the cervical cord

C6-C7 osteophyte

radiculopathy

C7; cervical radicu lopathy and
instability C6-C7 seconda ry to
lifting above head and twisting

interbody graft subsidence; C7-T1

foraminal na r r owing and bo ne s p ur

extending i nto the forame n on the

levels

levels

levels

level

levels

levels

Medtronic Page 77 of 103

wound exploration; repair of dural tear

C6-C7

leak

radiofrequency ab lation

pseudarthrosis; C2-C3 and C3-C4

degenerative arthropathy

Reoperation

C5-C7 exploration of fusion mass

C5-C6 &

C5-C6 halo around the screw; neck

pseudarthrosis)

453

No

Reoperation

C4-C5, C6-C7, and C7 -T1 left posterior

C4-C5 &

Left upper extremity r adiculopathy

accident

641

No

Reoperation

C5-C7 removal of anterior cervical

instrumentation

C5-C6 &

C4-C5 spondylosis

1494

Yes, both

Reoperation

C3-C4, C4-C5, C5-C6, C6 -C7

fusion stabi lization

C4-C5 &

Cervical stenosis, radiculopathy,

2007

No

Bone Growth

Stimulator

C5-C6 bone growth stimulator

C4-C5 &

C5-C6

C5-C6 nonunion; headaches

187

No

Bone Growth

Stimulator

C5-C6 bone growth stimulator

C4-C5 &

C5-C6

C5-C6 pseudarthrosis

188

No

Bone Growth

Bone growth stimulator

C5-C6 &

Fell postoperative day 9;

arm over head

188

No

Bone Growth

Stimulator

C6-C7 bone growth stimulator

C5-C6 &

C6-C7

C6-C7 nonunion

206

No

Bone Growth

Stimulator

C5-C6 bone growth stimulator

C5-C6 &

C6-C7

C5-C6 nonunion; fall; C4-C5

degenerative herniated disc

507

No

facet joints with severe

posteriorly

decompression

hardware; C4-C5 an terior cervical

discectomy and bilateral

foraminotom ies; C4-C5 anterior

interbody arthrodesis with allograft and

PEEK interv e r tebral body de vice; C4,

C5, C6, and C7 anterior cervical

explorati on with cervical

decompression, laminotomies, a nd

Stimulator

C6-C7

C5-C6

C6-C7

C5-C6

C6-C7

pain/burning (rule out C5-C6

and arm weakness; motor vehicle

and neck pain

headaches; diff iculty lifting r ig h t

* As of September 29, 2014.

Device-Related Adverse Events:
The relationship between adverse events and the implant and/or surgical procedure was assessed
separately by the Investigators and an independent Clinical Adjudication Committee (CAC)
according to the following classifications: implant associated, surgical procedure associated,
implant and surgical procedure associated, undetermined, and not related as outlined above. The
timecourse and total number and percentage of subjects who experienced an adverse event
classified by the CAC as either implant associated, or implant and surgical procedure associated
is provided in Table 39a and 39b by adverse event category.

Considering events classified by the CAC as either implant associated, or implant and surgical
procedure associated as device-related, through all available follow-up, 145 device-related events
occurred in 55 (26.3%) 2-level Prestige LP™ subjects and 123 device-related events occurred in
44 (23.4%) 2-level ACDF control subjects. Some of the more commonly reported device-related
adverse events through all available follow-up were cervical neck and/or arm pain (in 8.6% of 2­level Prestige LP™ subjects and 11.7% of 2-level ACDF control subjects), neurological adverse
events (in 7.2% of 2-level Prestige LP™ subjects and 5.9% of 2-level ACDF control subjects),
cervical study surgery spinal events (in 10.0% of 2-level Prestige LP™ subjects and 4.3% of 2­level ACDF control subjects), cervical Heterotopic Ossification (in 9.1% of 2-level Prestige
LP™ subjects and 2.1% of 2-level ACDF control subjects), implant adverse events (in 6.2% of
2-level Prestige LP™ subjects and 5.3% of 2-level ACDF control subjects), and non-union in the
2-level ACDF control group only (9.0%). Any numerical differences were most likely due to
chance based on examining a great number of categories for these events.

levels

Medtronic Page 78 of 103

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

(% of 209)

INV

(N)

CTR

(% of 188)

CTR

(N)

Total Adverse Events

18 5 29

35 8 16 1 21 3 12

19 7 27 0 35 (16.7%)

105

37 (19.7%)

96

DYSPHAGIA/DYSPHONIA

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

0 (0.0%)

0

Dysphagia

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

0 (0.0%)

0

HETEROTOPIC OSSIFICATION

0 0 0 1 0 1 0 1 0 1 3 0 7 0 9 (4.3%)

10

4 (2.1%) 4 Cervical

0 0 0 1 0 1 0 1 0 1 3 0 7 0 9 (4.3%)

10

4 (2.1%)

4

IMPLANT EVENTS

4 0 2 2 1 1 0 2 1 0 0 3 4 0 11 (5.3%)

12

6 (3.2%)

8

Breakage

1 0 0 1 0 0 0 1 0 0 0 0 0 0 1 (0.5%)

1

2 (1.1%)

2

Displacement

1 0 0 0 1 0 0 0 0 0 0 1 2 0 4 (1.9%)

4

1 (0.5%) 1 Displacement -Subsidence

0 0 0 0 0 1 0 0 1 0 0 1 1 0 2 (1.0%)

2

2 (1.1%)

2

Loosening

0 0 0 1 0 0 0 1 0 0 0 1 0 0 0 (0.0%)

0

3 (1.6%)

3

Malpositioning

2 0 1 0 0 0 0 0 0 0 0 0 0 0 3 (1.4%)

3

0 (0.0%)

0

Other

0 0 1 0 0 0 0 0 0 0 0 0 1 0 2 (1.0%)

2

0 (0.0%)

0

NECK AND/OR ARM PAIN

7 2 15

14 2 4 0 1 0 1 7 1 5 0

14 (6.7%)

36

16 (8.5%)

23

Cervical Neck Pain

4 1 8 5 0 2 0 1 0 1 4 1 3 0 13 (6.2%)

19

9 (4.8%)

11

Cervical Arm Pain

3 1 7 9 2 2 0 0 0 0 3 0 2 0 12 (5.7%)

17

10 (5.3%)

12

NEUROLOGICAL

4 1 9 6 4 8 1 3 1 0 1 0 0 0 13 (6.2%)

20

10 (5.3%)

18

Carpel Tunnel Syndrom e

0 0 1 0 0 0 0 0 0 0 0 0 0 0 1 (0.5%)

1

0 (0.0%) 0 Non-Specific or Other

0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%) 1 Spinal Cord Disturbanc e

0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%) 1 Upper Extremity-Motor

0 1 1 0 2 0 0 1 0 0 1 0 0 0 4 (1.9%)

4

2 (1.1%) 2 Upper Extremity- Sensory

4 0 7 6 2 5 1 2 1 0 0 0 0 0 10 (4.8%)

15

8 (4.3%)

13

Upper and Lower Extr emit y-Motor

0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%)

1

NON-UNION

0 0 0 1 0 0 0 7 0 4 0 2 0 0 0 (0.0%)

0

14 (7.4%)

14

OTHER

1 0 0 0 0 0 0 0 0 0 1 0 0 0 2 (1.0%)

2

0 (0.0%)

0

OTHER PAIN *

1 1 3 1 1 1 0 0 0 0 2 0 3 0 6 (2.9%)

10

3 (1.6%)

3

SPINAL EVENTS

1 0 0

10 0 1 0 7 1 5 4 1 8 0

13 (6.2%)

14

12 (6.4%)

24

Cervical (Study Surgery)

1 0 0 9 0 0 0 3 1 2 4 1 6 0 11 (5.3%)

12

7 (3.7%)

15

Cervical (Non-Study Surgery)

0 0 0 1 0 1 0 4 0 3 0 0 2 0 2 (1.0%)

2

7 (3.7%)

9

TRAUMA

0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 (0.0%)

0

1 (0.5%)

1

VASCULAR

0 0 0 0 0 0 0 0 0 0 1 0 0 0 1 (0.5%)

1

0 (0.0%)

0

Injury Intra-op

0 0 0 0 0 0 0 0 0 0 1 0 0 0 1 (0.5%)

1

0 (0.0%)

0

WOUND (NON-INFECTIOUS)

0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%)

1

CSF Leak

0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%)

1

Table 39a: Adverse Events Classified as Device-Related (Implant Associated or Implant and Surgical Procedure Associated)

by the Clinical Adjudication Committee through 24 Month Follow-up

# of Patients Reporting & Total adverse events

Subj.

(≤ 24 Months)

Events

Subj.

Events

Adverse Event

Surgery Peri-Op 6 Weeks 3 Months 6 Months 12 Mon ths 24 Months

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
*

Back and/or lower extremity (LE) pain ad verse events (AE’s) and He adache AE’s were classified as “Other Pain” AE’s for the Prestige LP™ IDE study.

Medtronic Page 79 of 103

# of Patients Reporting & Total adverse events

(≤ 120 Months)

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

INV

CTR

Total Adverse Events

9 3 6 1 9 7 0

10 8 4 6 0

55 (26.3%)

145

44 (23.4%)

123

DYSPHAGIA/DYSPHONIA

0 0 0 1 0 0 0 1 1 1 0 0 1 (0.5%)

1

3 (1.6%)

3

Dysphagia

0 0 0 1 0 0 0 1 1 1 0 0 1 (0.5%)

1

3 (1.6%)

3

HETEROTOPIC OSSIFICATION

1 0 1 0 3 0 0 0 4 0 3 0 19 (9.1%)

22

4 (2.1%)

4

Cervical

1 0 1 0 3 0 0 0 4 0 3 0 19 (9.1%)

22

4 (2.1%)

4

IMPLANT EVENTS

2 0 0 0 1 3 0 0 0 1 1 0 14 (6.7%)

16

10 (5.3%)

12

Breakage

1 0 0 0 0 0 0 0 0 0 0 0 2 (1.0%)

2

2 (1.1%)

2

Displacement

1 0 0 0 0 0 0 0 0 0 0 0 5 (2.4%)

5

1 (0.5%)

1

Displacement -Subsidence

0 0 0 0 1 0 0 0 0 0 0 0 3 (1.4%)

3

2 (1.1%)

2

Loosening

0 0 0 0 0 3 0 0 0 0 0 0 0 (0.0%)

0

6 (3.2%)

6

Malpositioning

0 0 0 0 0 0 0 0 0 0 0 0 3 (1.4%)

3

0 (0.0%)

0

Other

0 0 0 0 0 0 0 0 0 1 1 0 3 (1.4%)

3

1 (0.5%)

1

NECK AND/OR ARM PAIN

3 1 1 0 1 2 0 2 0 1 0 0 18 (8.6%)

42

22 (11.7%)

30

Cervical Neck Pain

2 1 1 0 1 2 0 2 0 1 0 0 16 (7.7%)

23

15 (8.0%)

18

Cervical Arm Pain

1 0 0 0 0 0 0 0 0 0 0 0 14 (6.7%)

19

10 (5.3%)

12

NEUROLOGICAL

0 0 3 0 0 1 0 0 0 0 0 0 15 (7.2%)

24

11 (5.9%)

19

Carpel Tunnel Syndrome

0 0 0 0 0 0 0 0 0 0 0 0 1 (0.5%)

1

0 (0.0%) 0 Non-Specific or Other

0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%) 1 Spinal Cord Disturbanc e

0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%) 1 Upper Extremity-Motor

0 0 1 0 0 0 0 0 0 0 0 0 5 (2.4%)

5

2 (1.1%) 2 Upper Extremity- Sensory

0 0 2 0 0 1 0 0 0 0 0 0 12 (5.7%)

18

9 (4.8%)

14

Upper and Lower Extrem ity-Motor

0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

1(0.5%)

1

NON-UNION

0 2 0 0 0 0 0 0 0 1 0 0 0 (0.0%)

0

17 (9.0%)

17

OTHER 0 0 0 0 0 0 0 0 0 0 0 0

2 (1.0%)

2

0 (0.0%)

0

OTHER PAIN*

0 0 0 0 0 0 0 1 0 0 0 0 6 (2.9%)

10

5 (2.7%)

5

SPINAL EVENTS

3 0 1 0 4 1 0 6 3 0 2 0 23 (11.0%)

27

12 (6.4%)

31

Cervical (Study Surgery)

3 0 1 0 4 1 0 6 1 0 2 0 21 (10.0%)

23

8 (4.3%)

22

Cervical (Non-Study Surgery)

0 0 0 0 0 0 0 0 2 0 0 0 4 (1.9%)

4

7 (3.7%)

9

TRAUMA

0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%)

1

VASCULAR

0 0 0 0 0 0 0 0 0 0 0 0 1 (0.5%)

1

0 (0.0%)

0

Injury Intra-op

0 0 0 0 0 0 0 0 0 0 0 0 1 (0.5%)

1

0 (0.0%)

0

WOUND (NON-INFECTIOUS)

0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%)

1

CSF Leak

0 0 0 0 0 0 0 0 0 0 0 0 0 (0.0%)

0

1 (0.5%)

1

Table 39b: Adverse Events Classified as Device-Related (Implant Associated or Implant and Surgical Procedure Associated) by

the Clinical Adjudication Committee through 120 Month Follow-up

36 Months 48 Months 60 Months 72 Months 84 Months 120 Months

Adverse Event

INV Subj.
(% of 209)

INV

Events (N)

CTR Subj.

(% of 188)

CTR

Events (N)

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
*

Back and/or lower extremity (LE) pain adverse events (AE’s) and Headache AE’s were classified as “Other Pain” AE’s for the Prestige LP™ IDE study.

Medtronic Page 80 of 103

IDE 24 Months

PAS 120 Month

INV (N=209)

CTR (N=188)

INV (N=209)

CTR (N=188)

Subjects

Events

Subjects

Events

Subjects

Events

Subjects

Events

n (%) N n (%) N n (%) N n (%)

N

TOTAL SEVERE D EVICE­RELATED ADVERSE EVENTS

DYSPHAGIA/DYSPHONIA

0 (0.0%)

0

0 (0.0%)

0

1 (0.5%)

1

1 (0.5%)

1

Dysphagia

0 (0.0%)

0

0 (0.0%)

0

1 (0.5%)

1

1 (0.5%)

1

HETEROTOPIC OSSIFICATION

0 (0.0%)

0

3 (1.6%)

3

0 (0.0%)

0

3 (1.6%)

3

0 (0.0%)

0

3 (1.6%)

3

0 (0.0%)

0

3 (1.6%)

3

IMPLANT EVENTS

2 (1.0%)

2

3 (1.6%)

4

2 (1.0%)

2

3 (1.6%)

4

Breakage

0 (0.0%)

0

1 (0.5%)

1

0 (0.0%)

0

1 (0.5%)

1

Displacement

1 (0.5%)

1

0 (0.0%)

0

1 (0.5%)

1

0 (0.0%)

0

Displacement - Subsidence

1 (0.5%)

1

1 (0.5%)

1

1 (0.5%)

1

1 (0.5%)

1

Loosening

0 (0.0%)

0

2 (1.1%)

2

0 (0.0%)

0

2 (1.1%)

2

NECK AND/OR ARM PAIN

2 (1.0%)

3

3 (1.6%)

3

3 (1.4%)

4

7 (3.7%)

8

Cervical Neck Pain

2 (1.0%)

2

3 (1.6%)

3

2 (1.0%)

2

7 (3.7%)

8

CERVICAL NEUROLOGICAL

0 (0.0%)

0

1 (0.5%)

1

1 (0.5%)

1

2 (1.1%)

2

Upper Extremity – Sensory

0 (0.0%)

0

1 (0.5%)

1

1 (0.5%)

1

2 (1.1%)

2

NON-UNION

0 (0.0%)

0

8 (4.3%)

8

0 (0.0%)

0

9 (4.8%)

9

OTHER

1 (0.5%)

1

0 (0.0%)

0

1 (0.5%)

1

0 (0.0%)

0

SPINAL EVENT

4 (1.9%)

5

5 (2.7%)

8

4 (1.9%)

5

5 (2.7%)

15

Cervical (Study Surgery)

4 (1.9%)

5

2 (1.1%)

4

4 (1.9%)

5

3 (1.6%)

11

Cervical (Non-Study Surgery)

0 (0.0%)

0

4 (2.1%)

4

0 (0.0%)

0

4 (2.1%)

4

TRAUMA

0 (0.0%)

0

1 (0.5%)

1

0 (0.0%)

0

1 (0.5%)

1

VASCULAR

1 (0.5%)

1

0 (0.0%)

0

1 (0.5%)

1

0 (0.0%)

0

Injury Intra-op

1 (0.5%)

1

0 (0.0%)

0

1 (0.5%)

1

0 (0.0%)

0

WOUND (NON-INFECTIOUS)

0 (0.0%)

0

1 (0.5%)

1

0 (0.0%)

0

1 (0.5%)

1

CSF Leak

0 (0.0%)

0

1 (0.5%)

1

0 (0.0%)

0

1 (0.5%)

1

Severe Device-Related Adverse Events:
Severity of adverse events was assessed according to the 4-tier World Health Organization
(WHO) Recommendations for Grading of Acute and Subacute Toxic Effects. Of the events
classified by the CAC as device-related, those classified as grade 3 or 4 according to the World
Health Organization Recommendations for Grading of Acute and Subacute Toxic Effects were
considered severe device-related adverse events. Through all available follow-up, 18 severe
device-related events occurred in 7 (3.3%) 2-level Prestige LP™ subjects and 46 severe device­related events occurred in 14 (7.4%) 2-level ACDF control subjects.

Some of the more commonly reported severe device-related adverse events through all available
follow-up were cervical neck and/or arm pain in 3 (1.4%) 2-level Prestige LP™ subjects and 7
(3.7%) 2-level ACDF control subjects, cervical study surgery spinal events in 4 (1.9%) 2-level
Prestige LP™ subjects and 3 (1.6%) 2-level ACDF control subjects, cervical non-study surgery
spinal events in zero 2-level Prestige LP™ subjects and 4 (2.1%) 2-level ACDF control subjects,
cervical Heterotopic Ossification in zero 2-level Prestige LP™ subjects and 3 (1.6%) 2-level
ACDF control subjects, implant adverse events in 2 (1.0%) 2-level Prestige LP™ subjects and 3
(1.6%) 2-level ACDF control subjects, and non-union in zero 2-level Prestige LP™ subjects and
9 (4.8%) 2-level ACDF control group subjects.

The total number and percentage of subjects who experienced an adverse event classified by the
CAC as severe (grade 3 or 4) and either implant associated, or implant and surgical procedure
associated by adverse event category is provided in Table 40.

Table 40: Adverse Events Classified as Severe (Grade 3 or 4) and Device-Related (Implant

Associated or Implant and Surgical Procedure Associated) by the Clinical Adjudication

Committee through 24 and 120 Month Follow-up

Adverse Event

5 (2.4%) 15 12 (6.4%) 29 7 (3.3%) 18 14 (7.4%) 46

Cervical

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACD F co ntrol (N=188)

Medtronic Page 81 of 103

Timepoint

Neurological Statu s

INV

CTR

6 weeks

Improved

Deteriorated

141/206 (68.4%)

29/206 (14.1%)

126/182 (69.2%)

31/182 (17.0%)

3 months

Improved

Deteriorated

147/205 (71.7%)

21/205 (10.2%)

119/178 (66.9%)

29/178 (16.3%)

6 months

Improved

Deteriorated

143/204 (70.1%)

19/204 (9.3%)

121/174 (69.5%)

24/174 (13.8%)

12 months

Improved

Deteriorated

142/203 (70.0%)

21/203 (10.3%)

109/165 (66.1%)

29/165 (17.6%)

24 months

Improved

Deteriorated

146/199 (73.4%)

17/199 (8.5%)

108/159 (67.9%)

22/159 (13.8%)

36 months

Improved

Deteriorated

134/185 (72.4%)

18/185 (9.7%)

97/148 (65.5%)

24/148 (16.2%)

60 months

Improved

Deteriorated

117/167 (70.1%)

16/167 (9.6%)

95/136 (69.9%)

17/136 (12.5%)

84 months

Improved

Deteriorated

109/154 (70.8%)

13/154 (8.4%)

81/123 (65.9%)

22/123 (17.9%)

120 months

Improved

Deteriorated

108/148 (73.0%)

11/148 (7.4%)

80/115 (69.6%)

16/115 (13.9%)

Neurological Status:
Neurological status was evaluated by assessment of motor function, sensory function, and
reflexes. Available neurological status data at 6 weeks, 3, 6, 12, 24, 36, 60, 84, and 120 months
is provided for the 2-level Prestige LP™ and 2-level ACDF control group subjects in Table 41
below. Neurologic success was defined as maintenance or improvement in all elements of
neurologic status compared to baseline. The success rates at 24 months post-operative were

91.5% for the 2-level Prestige LP™ group and 86.1% for the 2-level ACDF control group. At 24
months post-operative, there were numerically fewer subjects who exhibited neurologic
deterioration in the 2-level Prestige LP™ group (8.5%) as compared to the 2-level ACDF control
group (13.8%). The success rates at 120 months post-operative were 92.6% for the 2-level
Prestige LP™ group and 86.1% for the 2-level ACDF control group. At 120 months, there were
numerically fewer subject who exhibited neurologic deterioration in the 2-level Prestige LP™
group (7.4%) as compared to the 2-level ACDF control group (13.9%).

Table 41: Time course of Overall Neurological Status

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

Effectiveness Results

Stable

Stable

Stable

Stable

Stable

Stable

Stable

Stable

Stable

36/206 (17.5%)

37/205 (18.0%)

42/204 (20.6%)

40/203 (19.7%)

36/199 (18.1%)

33/185 (17.8%)

34/167 (20.5%)

32/154 (20.8%)

29/148 (19.6%)

25/182 (13.7%)

30/178 (16.9%)

29/174 (16.7%)

27/165 (16.4%)

29/159 (18.2%)

27/148 (18.2%)

24/136 (17.6%)

20/123 (16.3%)

19/115 (16.5%)

Primary Effectiveness Analysis:
The analysis of effectiveness was based on the as-treated cohort of 397 total subjects which
included all subjects who completed the surgical procedure and received a study device in either
treatment group according to the treatment received (209 2-level Prestige LP™ subjects and 188
2-level ACDF control subjects).

The primary endpoint was a composite endpoint (Overall Success Protocol Definition) that
defined a subject as a success if the following criteria were met at 24 months for IDE and 120

Medtronic Page 82 of 103

months for PAS post-operative:

• Improvement (reduction) of at least 15 points in NDI score compared to pre-operative

baseline;

• Maintenance or improvement in neurological status compared to pre-operative baseline as

measured based on motor function, sensory function, and reflexes;

• No serious adverse event classified as implant associated, or implant/surgical procedure

associated; and

• No additional surgical procedure classified as a “failure.”

As described above, because the additional surgical procedure component of the primary
endpoint did not consider all subsequent surgeries at the index level as failures, FDA requested
an additional analysis of overall success in which all subsequent surgeries at the index level and
all intra-operative treatment conversions were considered failures (referred to as Overall Success
Alternate Analysis in Table 42a below).

Overall study success criteria were based on a comparison of individual subject success rates,
such that the subject success rate for the 2-level Prestige LP™ group was required to be non­inferior to that of the 2-level ACDF control group. The study was designed as a non-inferiority
study with a margin (delta) of 10%. Non-inferiority was to be claimed if the posterior probability
that the success rate in the 2-level Prestige LP™ group was not lower than the success rate in the
2-level ACDF control group by more than 10% was greater than 95%.

The observed success rates at 24 and 120 months post-operative for each of the overall success
components and composite overall success as well as the Bayesian analyses are provided in
Table 42a. The posterior means for each treatment group can be interpreted as the average
chance of component or overall success at the timepoint, and the posterior mean of the difference
between the two treatment groups can be interpreted as the average difference in the chance of
component or overall success at the timepoint. For example,

At 24 Months,
When a subject receives the 2-level Prestige LP™ device, the average chance of overall
(composite) success as defined in the clinical study is 80.3%, and there is a 95% probability that
the chance of success ranges from 75.0% to 85.8%. Similarly, given the results of the study,
when a subject receives the 2-level ACDF control treatment, the average chance of overall
(composite) success is 69.0%, and there is a 95% probability that the chance of overall success
ranges from 61.8% to 75.7%. Then the average difference in the chanc e of overal l success
between the 2-level Prestige LP™ group and the 2-level ACDF control group at 24 months is

11.3% with 95% probability that this difference falls in the range of 2.2% to 20.1%.

At 120 Months,
When a subject receives the 2-level Prestige LP™ device, the average chance of overall
(composite) success as defined in the clinical study is 80.0%, and there is a 95% probability that
the chance of success ranges from 73.5% to 86.2%. Similarly, given the results of the study,
when a subject receives the 2-level ACDF control treatment, the average chance of overall
(composite) success is 62.0%, and there is a 95% probability that the chance of overall success
ranges from 53.4% to 70.6%. The average difference in the chance of overall success between
the 2-level Prestige LP™ group and the 2-level ACDF control group at 120 months is 18.0%

Medtronic Page 83 of 103

Primary

24-Month

Probabilities

120-Month

Probabilities

Non-

ity

Non-

ity

NDI Success

improvement)*

87.1%

91.7%)

78.3%

84.1%)

8.8%

16.7%)

87.9%

92.9%)

76.1%

83.5%)

11.9%

21.3%)

Neurological

improvement)*

Serious implant

AE**

Additional

“failure”*

Overall success

Definition)

80.3%

85.8%)

69.0%

75.7%)

11.3%

20.1%)

80.0%

86.2%)

62.0%

70.6%)

18.0%

28.7%)

Overall Success

Analysis***)

79.5%

84.8%)

68.5%

75.3%)

11.0%

19.8 %)

78.9%

85.3%)

59.0%

67.8%)

19.9%

30.7%)

~100.0

Outcome

Component

(≥15 point

Success
(maintenance/

with 95% probability that this difference falls in the range of 7.3% to 28.7%.

For overall success, the posterior probability of non-inferiority of the 2-level Prestige LP™
group to the 2-level ACDF control group at 24 and 120 months post-operative is essentially
100%, demonstrating non-inferiority. In addition, the posterior probability of superiority of the
2-level Prestige LP™ group to the 2-level ACDF control group at 24 and 120 months post­operative is above the 95% threshold, demonstrating statistical superiority. For the component
endpoints of NDI and neurological status, multiple comparisons were carried out without
adjustment for multiplicity. For NDI success, both non-inferiority and superiority could be
claimed at 24 months and 120 months. For Neurological success, non-inferiority could be
claimed at 24 months and 120 months.

Table 42a: Observed Component and Overall Success Rates and Posterior Probabilities of

Success at 24 and 120 Months

24-Month Observed

Success Rate

INV CTR INV CTR

175/199
(87.9%)

182/199
(91.5%)

126/159
(79.2%)

137/159
(86.2%)

24-Month Posterior Mean

(95% HPD Credible Interval)

(82.6%,

90.2%

(86.2%,

94.2%)

(71.9%,

85.2%

(80.0%,

90.6%)

INV -

CTR

(1.2%,

5.0%

(-1.4%,

11.9%)

Posterior

Inferior

~100.0% 99.0% 130/147

~100.0% 93.1% 137/148

Super

iority

120-Month Observed

Success Rate

INV CTR INV CTR

(88.4%)

(92.6%)

88/115

(76.5%)

99/115

(86.1%)

120-Month Posterior Mean

(82.6%,

92.0%

(87.7%,

96.1%)

(68.2%,

85.5%

(79.0%,

91.6%)

INV -

CTR

(2.7%,

6.5%

(-1.1%,

14.3%)

Posterior

Inferior

~100.0

%

~100.0

%

Superio

rity

99.5%

95.6%

or
implant/surgical
procedure
associated

surgical
procedure
classified as

(Protocol

(Alternate

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACD F co ntrol (N=188)
* Analyses were conducted without adjustment for multiplicity.
** For the “Serious implant or implant/surgical procedure associated AE” and “Additional surgical procedure classified as failure” rows, only the

***All subsequent surgeries at index level and all intra-operative anatomical/technical difficulties considered failures.

2 11 Not Available 7 14 Not Available

4 12 Not Available 8 19 Not Available

162/199
(81.4%)

162/201
(80.6%)

111/160

(69.4%)

110/160

(68.8%)

(75.0%,

(73.7%,

(61.8%,

(61.5%,

(2.2%,

(2.0%,

~100.0

~100.0% 99.3% 119/150

%

99.3% 119/148
(80.4%)

(79.3%)

74/119

(62.2%)

71/120

(59.2%)

(73.5%,

(72.4%,

(53.4%,

(50.4%,

(7.3%,

(9.1%,

~100.0

%

~100.0

%

number of subjects experiencing these events were presented.

In addition, the observed success rates at 36-, 60- and 84-months post-operative for each of the
overall success components and composite overall success as well as the Bayesian analyses are
respectively provided in Table 42b. The investigational group consistently demonstrate
superiority over the control group for overall success and its component NDI success at all
timepoints from 24 to 120 months.

99.9%

%

Medtronic Page 84 of 103

36-Month

Probabilities

60-Month

Probabilities

84-Month

Probabilities

(INV vs CTR)

(INV vs CTR)

(INV vs CTR)

Non-

rity

Supe

y

Non-

ity

Non-

ity

Neurological

improvement)*

Serious implant or

associated AE**

Additional surgical

“failure”*

Overall Success

Analysis***)

80.4%

85.9%)

68.4%

75.7%)

12.0%

21.3%)

78.4%

84.4%)

63.8%

71.6%)

14.5%

24.5%)

77.2%

83.6%)

58.5%

66.9%)

18.8%

29.4%)

Table 42b: Observed Component and Overall Success Rates and Posterior Probabilities of Success at 36, 60 and 84 Months

Primary

Outcome

Component

NDI Success (≥15

point
improvement)*

Success
(maintenance/

implant/surgical
procedure

procedure
classified as

Overall success
(Protocol
Definition)

(Alternate

36-Month

Observed Success

Rate

INV CTR INV CTR

166/185
(89.7%)

167/185
(90.3%)

121/147
(82.3%)

124/148
(83.8%)

4 12 Not Available 5 13 Not Available 6 13 Not Available

6 13 Not Available 7 16 Not Available 7 17 Not Available

151/185
(81.6%)

151/187
(80.7%)

105/150
(70.0%)

103/150
(68.7%)

36-Month Posterior Mean

(95% HPD Credible

Interval)

INV -

CTR

89.3%

(84.8%,

93.6%)

89.8%

(85.5%,

94.0%)

81.3%

(75.7%,

86.8%)

(74.7%,

81.9%

(75.7%,

87.9%)

83.3%

(77.3%,

89.1%)

69.7%

(62.5%,

77.0%)

(61.1%,

(-0.1%,

15.1%)

(-0.8%,

13.9%)

11.5%

(2.3%,

20.7%)

(2.8%,

7.4%

6.5%

Posterior

Inferio

riorit

~100.0% 97.5

%

~100.0% 96.1

%

~100.0% 99.3

%

~100.0% 99.5

%

60-Month
Observed

Success Rate

60-Month Posterior Mean

(95% HPD Credible

Interval)

INV CTR INV CTR

149/167

(89.2%)

151/167

(90.4%)

133/167

(79.6%)

133/169

(78.7%)

105/135
(77.8%)

119/136
(87.5%)

91/139

(65.5%)

89/139

(64.0%)

88.8%

(83.9%,

93.3%)

89.9%

(85.3%,

94.2%)

79.3%

(73.1%,

85.2%)

(72.1%,

77.4%

(70.4%,

84.3%)

87.0%

(81.3%,

92.4%)

65.2%

(57.4%,

73.0%)

(55.9%,

INV -

CTR

11.4%
(2.9%,

19.8%)

3.0%

(-4.2%,

10.3%)

14.0%
(4.1%,

24.0%)

(4.5%,

Posterior

Inferior

Super

iority

~100.0% 99.6

%

~100.0% 79.4

%

~100.0% 99.7

%

~100.0% ~99.8

%

84-Month
Observed

Success Rate

84-Month Posterior Mean

(95% HPD Credible

Interval)

INV CTR INV CTR

134/154
(87.0%)

141/154
(91.6%)

121/154
(78.6%)

121/156
(77.6%)

93/123

(75.6%)

101/123
(82.1%)

79/127

(62.2%)

75/128

(58.6%)

86.5%

(81.2%,

91.7%)

91.0%

(86.5%,

95.3%)

78.2%

(71.7%,

84.5%)

(70.6%,

75.2%

(67.7%,

82.7%)

81.6%

(74.8%,

88.2%)

62.0%

(53.6%,

70.3%)

(50.1%,

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACD F co ntrol (N=188)
* Analyses were conducted without adjustment for multiplicity.
** For the “Serious implant or implant/surgical procedure associated AE” and “Additional surgical procedure classified as failure” rows, only the number of subjects experiencing these events were

presented.

***All subsequent surgeries at index level and all intra-operative anatomical/technical difficulties considered failures.

INV -

CTR

11.3%

(2.1%,

20.6%)

9.4%

(1.5%,

17.7%)

16.2%

(5.6%,

26.7%)

(8.1%,

Posterior

Inferior

Superi

ority

~100.0% 99.3

%

~100.0% 99.0

%

~100.0% 99.9

%

~100.0% ~100.

0%

Medtronic Page 85 of 103

Serious implant or

associated AE*

Additional surgical

“failure”*

Superior C3-C4

Inferior C4-C5

Superior C4-C5

Inferior C5-C6

Superior C5-C6

Inferior C6-C7

INV

CTR

INV

CTR

INV

CTR

6 Months

Statistics*

3/3 (100%)

2/3 (66.7%)

33/42 (78.6%)

29/41 (70.7%)

133/158 (84.2%)

95/130 (73.1%)

33.3% (-26.3%, 93.0%)

7.8% (-10.9%, 26.5%)

11.1% (1.7%, 20.5%)

12 Months

Statistics*

2/2 (100%)

1/2 (50.0%)

32/41 (78.0%)

28/40 (70.0%)

133/159 (83.6%)

88/124 (71.0%)

50.0% (-34.9%, 100%)

8.0% (-11.0%, 27.1%)

12.7% (3.0%, 22.4%)

24 Months

Statistics*

1/2 (50.0%)

1/2 (50.0%)

31/39 (79.5%)

28/39 (71.8%)

130/158 (82.3%)

82/119 (68.9%)

0.0% (-98.0%, 98.0%)

7.7% (-11.4%, 26.7%)

13.4% (3.3%, 23.5%)

36 Months

Statistics*

3/3 (100%)

1/2 (50.0%)

33/40 (82.5%)

24/37 (64.9%)

115/142 (81.0%)

80/111 (72.1%)

50.0% (-21.6%, 100%)

17.6% (-2.0%, 37.2%)

8.9% (-1.5%, 19.4%)

60 Months

Statistics*

0/1 (0.0%)

0/1 (0.0%)

26/35 (74.3%)

23/31 (74.2%)

107/131 (81.7%)

68/107 (63.6%)

Not Available

0.1% (-21.0%, 21.2%)

18.1% (6.9%, 29.4%)

84 Months

0/1 (0.0%)

0/1 (0.0%)

27/34 (79.4%)

20/29 (69.0%)

94/119 (79.0%)

59/97 (60.8%)

Not Available

10.4% (-11.1%, 32.0%)

18.2% (6.0%, 30.4%)

120 Months

0/1 (0.0%)

0/1 (0.0%)

25/33 (75.8%)

18/28 (64.3%)

94/114 (82.5%)

56/90 (62.2%)

Not Available

11.5% (-11.5%, 34.4%)

20.2% (8.0%, 32.4%)

Table 43 provides data on the timecourse of overall success rates for both treatment groups for
Overall Success (Protocol Defined) and Overall Success (Alternate Analysis).

Table 43: Time Course of Observed Success Rates

Primary Outcome

Component

6 Months 12 Months 24 Months 36 Months 60 Months 84 Months 120 Months

INV CTR INV CTR INV CTR INV CTR INV CTR INV CTR INV CTR

NDI Success (≥15 point

improvement)

Neurological Success
(maintenance/ improvement)

implant/surgical procedure

procedure classified as

Overall success (Protocol
Definition)

Overall Success (Alternate
Analysis**)

185/203
(91.1%)

185/204
(90.7%)

169/203
(83.3%)

169/205
(82.4%)

141/172

183/202

(82.0%)

150/174

182/203

(86.2%)

0 6 1 8 2 11 4 12 5 13 6 13 7 14

1 4 2 9 4 12 6 13 7 16 7 17 8 19

126/174

167/202

(72.4%)

126/174

167/204

(72.4%)

(90.6%)

(89.7%)

(82.7%)

(81.9%)

136/165
(82.4%)

136/165
(82.4%)

117/166
(70.5%)

117/166
(70.5%)

175/199
(87.9%)

182/199
(91.5%)

162/199
(81.4%)

162/201
(80.6%)

126/159
(79.2%)

137/159
(86.2%)

111/160
(69.4%)

110/160
(68.8%)

166/185
(89.7%)

167/185
(90.3%)

151/185
(81.6%)

151/187
(80.7%)

121/147
(82.3%)

124/148
(83.8%)

105/150
(70.0%)

103/150
(68.7%)

149/167

(89.2%)

151/167

(90.4%)

133/167

(79.6%)

133/169

(78.7%)

105/135
(77.8%)

119/136
(87.5%)

91/139

(65.5%)

89/139

(64.0%)

134/154
(87.0%)

141/154
(91.6%)

121/154
(78.6%)

121/156
(77.6%)

93/123

(75.6%)

101/123
(82.1%)

79/127

(62.2%)

75/128

(58.6%)

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
* For the “Serious implant or implant/surgical procedure associated AE” and “Additional surgical procedure classified as failure” rows, only the
number of subjects experiencing these events were presented.
** All subsequent surgeries at index level and all intra-operative anatomical/technical difficulties considered failures.
Note: To be consistent with how NDI and neurological status success are determined, the subsequent surgery determination for the overall
success timecour se table is based o n the subject fo llow-up visit. For example, if a subseq uent surgery occurred before the 6 month-visit, then it
was counted as a failure at 6 months. If the subsequent surgery occurred af ter the 6-month visit, even if it was still within the 6-month visit
window, it was counted as a failure at 12 months.

Table 44 provides overall success data for each treatment group stratified by the treated levels
including post-hoc statistical analysis and comparisons between the 2-level Prestige LP™ group
and the 2-level ACDF control group through the 120 months timepoint using Frequentist
methods. Overall success rates were not significantly different between the 2-level Prestige LP™
group and the 2-level ACDF control group at any treatment levels except for at the C5-C6
(superior) and C6-C7 (inferior) adjacent levels in which the 2-level Prestige LP™ group had a
significantly higher success rate compared to the 2-level ACDF control group at all time periods
with the exception of the 36-month period.

Table 44: Timecourse of Observed Overall Success (Protocol Definition)

Rates by Level Treated

130/147
(88.4%)

137/148
(92.6%)

119/148
(80.4%)

119/150
(79.3%)

88/115

(76.5%)

99/115

(86.1%)

74/119

(62.2%)

71/120

(59.2%)

Timepoint

Statistics*

Statistics*

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
* Point Estimate and 95% Confidence Interval of Difference of Success Rate betwe en 2-level Prestige LP™ and 2-level ACDF control. The 95%
CI was provided using Frequentist Farrington and Manning methods.

Medtronic Page 86 of 103

Non-

(N = 14)

Non-

(N = 16)

Non-

(N = 14)

Non-

(N = 16)

Serious implan t- or

associat ed AE

Neurological

improvement)

Serious implan t- or

associat ed AE

Post-hoc subgroup analyses examining the primary endpoint (Overall Success Protocol
Definition) stratified by subject gender and race at the 24 and 120 month timepoints were
conducted, and the results for race are provided in Tables 4545a and the results for gender are
provided in Table 45b. Due to the relatively small numbers of non-Caucasians treated in the IDE
study, statistical conclusion regarding overall success outcomes based on race cannot be reliably
made; however, qualitative differences were not observed. The rates for the primary outcome
components were similar between males and females within each study group. The 2-level
Prestige LP™ overall success rates were qualitatively higher than the 2-level ACDF control
group success rates in all subgroups.

Table 45a: Overall Success (Protocol Definition) by Subject Race at 24 and

120 months

IDE 24 Month PAS 120 Month

Primary Out come

Component

NDI Success (≥15

point improvement)
Neurological

Success
(maintenance/
improvement)

implant/surgical
procedure-

Additional surgical
procedur e classified
as “failure”

Overall Success
(Protocol
Definition)

INV=2-level Prestige LP™ (N=209); CTR = 2-le vel ACDF control (N=188)

INV CTR INV CTR

Caucasian

(N = 195)

162/185
(87.6%)

169/185
(91.4%)

2 0 9 2 7 0 12 2

4 0 10 2 8 0 17 2

150/185
(81.1%)

Caucasian

13/14

(92.9%)

13/14

(92.9%)

12/14

(85.7%)

Caucasian

(N = 172)

115/146
(78.8%)

126/146
(86.3%)

102/147
(69.4%)

Caucasian

11/13

(84.6%)

11/13

(84.6%)

9/13

(69.2%)

Caucasian

(N = 195)

121/138
(87.7%)

128/139
(92.1%)

110/139
(79.1%)

Caucasian

9/9

(100%)

9/9

(100%)

9/9

(100%)

Caucasian

(N = 172)

81/106

(76.4%)

91/106

(85.8%)

68/110

(61.8%)

Caucasian

7/9

(77.8%)

8/9

(88.9%)

6/9

(66.7%)

Table 45b: Overall Success (Protocol Definition) by Subject Gender at 24

and 120 months

IDE 24 Month PAS 120 Month

Primary Out come

Component

NDI Success (≥15

point improvement)

Success
(maintenance/

implant/surgical
procedure-

(N = 92)

(88.5%)

(92.0%)

INV CTR INV CTR

Male

77/87

80/87

1 1 7 4 3 4 9 5

Female

(N = 117)

98/112

(87.5%)

102/112
(91.1%)

Male

(N = 90)

58/76

(76.3%)

66/76

(86.8%)

Female

(N = 98)

68/83

(81.9%)

71/83

(85.5%)

Male

(N = 92)

48/57

(84.2%)

53/58

(91.4%)

Female

(N = 117)

82/90

(91.1%)

84/90

(93.3%)

Male

(N = 172)

43/58

(74.1%)

47/58

(81.0%)

Female

(N = 98)

45/57

(78.9%)

52/57

(91.2%)

Medtronic Page 87 of 103

Additional surgical

as “failure”

Overall Success

Definition)

24-Month

Success Rate

120-Month

Success Rate

INV

CTR

INV

CTR

INV - CTR

INV

CTR

INV

CTR

INV - CTR

96.9%

99.0%)

94.8%

97.7%)

96.6%

99.2%

91.5%

96.1%)

Neck pain

baseline)

88.0%

92.4%)

88.9%

93.3%)

88.6%

93.5%)

88.9%

94.2%)

Arm pain

baseline)

89.6%

93.6%)

87.2%

92.1%)

81.6%

87.7%)

82.5%

89.1%)

SF-36 PCS

79.6%

84.9%)

74.9%

81.3%)

69.4%

76.7%)

70.2%

78.4%)

68.8%

75.3%)

71.2%

77.8%)

72.8%

79.8%)

70.2%

78.4%)

improvement)

50.9%

57.5%)

43.9%

51.4%)

52.4%

60.4%)

48.2%

57.4%)

Gait assessment

status)

IDE 24 Month PAS 120 Month

Primary Out come

INV CTR INV CTR

Component

procedur e classified

(Protocol

Male

(N = 92)

1 3 7 3 2 6 12 7

72/87

(82.8%)

Female

(N = 117)

90/112

(80.4%)

Male

(N = 90)

52/77

(67.5%)

Female

(N = 98)

59/83

(71.1%)

Male

(N = 92)

45/58

(77.6%)

Female

(N = 117)

74/90

(82.2%)

Male

(N = 172)

35/60

(58.3%)

Female

(N = 98)

39/59

(66.1%)

Secondary Effectiveness Analysis

Clinical Endpoints:
In addition to the components of the primary endpoint presented above, secondary effectiveness
variables were also assessed. Tables 46 describe the results of the secondary effectiveness
endpoints at 24 months and 120 months, respectively. The results were comparable between the
2-level Prestige LP™ group and the 2-level ACDF control group with the exception of neck
pain success alternative definition (at least 2 points improvement), which shows that the
investigational group has statistically higher percentage of subjects having neck pain improved
at least 2 points than that in the control group at both 24 months and 120 months.

Table 46: Summary of Secondary Effectiveness Endpoints at 24 and 120 Months

Outcome
Measure

Observed

24-Month Posterior Mean

(95% HPD Credible Interval)

Observed

120-Month Posterior Mean

(95% HPD Credible Interval)

Neck pain
(any improvement)

(≥2/10 point

decrease in neck
pain intensity from

Arm pain
(any improvement)

(≥2/10 point

decrease in arm
pain intensity from

SF-36 PCS
(any improvement)

(≥15%

improvement)
SF-36 MCS

(any improvement)
SF-36 MCS

(≥15%

(maintenance or
improvement of
pre-operative

195/199
(98.0%)

185/199
(93.0%)

177/199
(88.9%)

169/199
(84.9%)

178/197
(90.4%)

158/197
(80.2%)

136/197
(69.0%)

100/197
(50.8%)

199/199

(100%)

152/159
(95.6%)

136/159
(85.5%)

143/159
(89.9%)

130/159
(81.8%)

137/156
(87.8%)

118/156
(75.6%)

113/156
(72.4%)

69/156

(44.2%)

157/159
(98.7%)

(94.4%,

91.7%

(87.9%,

95.4%)

(83.6%,

83.8%

(78.7%,

88.7%)

(85.5%,

(74.1%,

(62.5%,

(43.8%,

99.0%

(97.7%,

100%)

(91.4%,

84.9%

(79.3%,

90.0%)

(84.0%,

81.2%,

(75.1%,

86.9%)

(82.1%,

(68.2%,

(64.0%,

(36.5%,

97.7%

(95.5%,

99.5%)

2.1%

(-1.9%, 6.2%)

6.9%

(0.2%, 13.4%)

-0.8%

(-7.3%, 5.6%)

2.6%

(-5.1%, 10.5%)

2.4%

(-4.2%, 8.8%)

4.7%

(-4.2%, 12.8%)

-2.4%

(-12.0%, 6.7%)

7.0%

(-3.6%, 17.0%)

1.3%

(-1.3%, 4.0%)

142/146
(97.3%)

137/147
(93.2%)

131/147
(89.1%)

123/147
(83.7%)

119/145
(82.1%)

101/145
(69.7%)

106/145
(73.1%)

76/145

(52.4%)

145/148
(98.0%)

106/115
(92.2%)

97/115

(84.3%)

103/115
(89.6%)

92/115

(80.0%)

93/112

(83.0%)

79/112

(70.5%)

79/112

(81.3%)

54/112

(48.2%)

107/115
(93.0%)

(93.7%,

92.6%

(88.3%,

96.5%)

(83.4%,

83.2%

(77.1%,

89.0%)

(75.3%,

(61.9%,

(65.6%,

(44.4%,

97.3%

(94.7%,

99.5%)

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

(86.3%,

83.8%

(77.0%,

90.2%)

(83.1%,

79.5%

(72.1%,

86.5%)

(75.4%,

(61.7%,

(61.8%,

(39.2%,

92.3%

(87.4%,

96.7%)

5.2%

(-0.5%, 11.2%)

8.9%

(1.0%, 16.8%)

-0.3%

( -7.9%, 7.3%)

3.7%

(-5.7%, 13.2%)

-0.8%

(-10.2%, 8.5%)

-0.8%

(-11.9, 10.4%)

2.6%

(-8.3%, 13.7%)

4.1%

(-7.9%, 16.4%)

5.0%

(-0.2%, 10.7%)

Medtronic Page 88 of 103

120-Month Observed

Mean (Std) [p-value]*

120-Month Posterior Mean

(95% HPD Credible Interval)

Posterior

Superiority

INV

CTR

INV

CTR

INV - CTR

Baseline

[< 0.001]

[<0.001]

(34.6%, 40.6%)

(26.4%, 34.0%)

(2.5%, 12.3%)

Improvement of SF-36 PCS

12.9 (12.5)

12.2 (11.2)

12.9%

12.2%

0.7%

Improvement of SF-36 MCS

9.1 (12.5)

6.5 (13.0)

9.1%

6.5%

2.6%

84-Month Observed

Mean (Std) [p-value]*

84-Month Posterior Mean

(95% HPD Credible Interval)

Posterior

Superiority

INV

CTR

INV

CTR

INV - CTR

Improvement of Neck Pain
From Baseline

12.1 (5.4)
[<0.001]

10.0 (5.7)
[<0.001]

12.1%

(11.2%, 13.0%)

10.0%

(9.0%, 11.0%)

2.1%

(0.8%, 3.4%)

Improvement of SF-36 PCS
From Baseline

13.8 (12.1)
[<0.001]

12.3 (12.3)
[<0.001]

13.8%

(11.9%, 15.7%)

12.3%

(10.1%, 14.5%)

1.5%

(-1.4%, 4.4%)

60-Month Observed

Mean (Std) [p-value]*

60-Month Posterior Mean

(95% HPD Credible Interval)

Posterior

Superiority

INV

CTR

INV

CTR

INV - CTR

Baseline

[<0.001]

[<0.001]

(34.8%, 40.2%)

(26.9%, 33.5%)

(3.0%, 11.6%)

Improvement of Neck Pain
From Baseline

12.1 (5.6)

[<0.001]

9.6 (5.7)
[<0.001]

12.1%

(11.3%, 12.9%)

9.6%

(8.6%, 10.6%)

2.5%

(1.2%, 3.8%)

From Baseline

[<0.001]

[<0.001]

(9.7%, 11.7%)

(8.4%, 10.6%)

(-0.3%, 2.7%)

Improvement of SF-36 PCS
From Baseline

15.9 (12.3)
[<0.001]

11.9 (11.8)
[<0.001]

15.9%

(14.0%, 17.8%)

11.9%

(9.9%, 13.9%)

4.0%

(1.2%, 6.8%)

Improvement of SF-36
MCS From Baseline

8.7 (12.9)

[<0.001]

7.3 (13.1)
[<0.001]

8.7%

(6.7%, 10.7%)

7.3%

(5.1%, 9.5%)

1.4%

(-1.6%, 4.4%)

In addition, Table 46b, 46c, 46d and 46e summarize the results of the improvement of
effectiveness measurement (such as NDI score, SF-36 scores, and neck and arm pain scores)
from baseline to 120, 84, 60 and 36 months for each treatment group, and comparisons were also
compared between the treatment groups. Both groups improved significantly over preoperative
on all of these measures (all p≤0.001), with the 2-level Prestige LP™ group showing superiority
at all intervals for improvements in NDI score [Posterior Probability of Superiority (PPS)
=99.9% at 120 months, PPS=99.5% at 84 months, PPS=~100.0% at 60 months, PPS=99.6% at
36 months) and neck pain score (PPS=~100.0% at 120 months, PPS=99.9% at 84 months,
PPS=~100.0% at 60 months, PPS=99.9% at 36 months). Mean improvements from preoperative
in arm pain score and SF-36 PCS were numerically better for 2-level Prestige LP™ group than
2-level ACDF control group at all the long-term intervals but did not consistently show statistical
superiority.

Table 46b: Summary of Improvement of Effectiveness Measurements from Baseline at 120 Months

Outcome Measure

Improvement of NDI From

Improvement of Neck Pain
From Baseline

Improvement of Arm Pain
From Baseline

From Baseline

From Baseline

37.6 (18.7)

12.5 (5.2)
[< 0.001]

10.5 (7.0)
[< 0.001]

[< 0.001]

[< 0.001]

30.2 (21.0)

9.8 (5.7)

[< 0.001]

9.8 (6.9)

[< 0.001]

[< 0.001]

[< 0.001]

37.6%

12.5%

(11.7%, 13.3%)

10.5%

(9.4%, 11.6%)

(10.9%, 14.9%)

(7.1%, 11.1%)

30.2%

9.8%

(8.8%, 10.8%)

9.8%

(8.5%, 11.1%)

(10.1%, 14.3%)

(4.1%, 8.9%)

7.4%

2.7%

(1.4%, 4.0%)

0.7%

(-1.0%, 2.4%)

(-2.2%, 3.6%)

(-0.6%, 5.8%)

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
*p-value is for testing whether the improvement from baseline is significantly greater than 0.

Table 46c: Summary of Improvement of Effectiveness Measurements from Baseline at 84 Months

Outcome Measure

Improvement of NDI From
Baseline

Improvement of Arm Pain
From Baseline

Improvement of SF-36 MCS
From Baseline

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
*p-value is for testing whether the improvement from baseline is significantly greater than 0.

36.4 (18.6)

[<0.001]

10.2 (7.2)
[<0.001]

9.6 (12.3)
[<0.001]

30.3 (20.0)
[<0.001]

9.9 (6.4)
[<0.001]

7.1 (12.2)
[<0.001]

36.4%

(33.5%, 39.3%)

10.2%

(9.1%, 11.3%)

9.6%

(7.6%, 11.6%)

30.3%

(26.8%, 33.8%)

9.9%

(8.8%, 11.0%)

7.1%

(4.9%, 9.3%)

6.1%

(1.5%, 10.7%)

0.3%

(-1.3%, 1.9%)

2.5%

(-0.4%, 5.4%)

Probability of

99.9%

~100.0%

79.1%

68.2%

94.7%

Probability of

99.5%

99.9%

64.3%

84.2%

95.2%

Table 46d: Summary of Improvement of Effectiveness Measurements from Baseline at 60 Months

Outcome Measure

Improvement of NDI From

Improvement of Arm Pain

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

Medtronic Page 89 of 103

37.5 (18.1)

10.7 (6.7)

30.2 (19.5)

9.5 (6.5)

37.5%

10.7%

30.2%

9.5%

7.3%

1.2%

Probability of

~100.0%

~100.0%

94.2%

99.8%

82.0%

36-Month Observed

Mean (Std) [p-value]*

36-Month Posterior Mean

(95% HPD Credible Interval)

Posterior

Superiority

INV

CTR

INV

CTR

INV - CTR

Improvement of NDI
From Baseline

37.1 (17.4)
[<0.001]

31.8 (18.5)
[<0.001]

37.1%

(34.6%, 39.6%)

31.8%

(28.8%, 34.8%)

5.3%

(1.4%, 9.2%)

Improvement of Arm Pain
From Baseline

10.7 (6.4)
[<0.001]

10.6 (6.3)
[<0.001]

10.7%

(9.8%, 11.6%)

10.6%

(9.6%, 11.6%)

0.1%

(-1.3%, 1.5%)

Improvement of SF-36
PCS From Baseline

14.9 (11.8)
[<0.001]

14.0 (10.5)
[<0.001]

14.9%

(13.2%, 16.6%)

14.0%

(12.3%, 15.7%)

0.9%

(-1.5%, 3.3%)

Improvement of SF-36
MCS From Baseline

9.4 (13.1)
[<0.001]

7.1 (12.3)
[<0.001]

9.4%

(7.5%, 11.3%)

7.1%

(5.1%, 9.1%)

2.3%

(-0.5%, 5.1%)

*p-value is for testing whether the improvement from baseline is significantly greater than 0.

Table 46e: Summary of Improvement of Effectiveness Measurements from Baseline at 36 Months

Outcome Measure

Improvement of Neck
Pain From Baseline

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)
*p-value is for testing whether the improvement from baseline is significantly greater than 0.

12.1 (5.0)
[<0.001]

10.3 (5.4)
[<0.001]

12.1%

(11.4%, 12.8%)

10.3%

(9.4%, 11.2%)

1.8%

(0.7%, 2.9%)

Probability of

Radiographic Endpoints:

Radiographic Success:

The protocol-specified radiographic success criteria for 2-level Prestige LP™ subjects required
angular motion on lateral flexion/extension radiographs >4° but <20° with no radiographic
evidence of bridging trabecular bone that forms a continuous bony connection with the vertebral
bodies (i.e., no bridging bone) at both treated levels.

In the 2-level ACDF control group, radiographic success was fusion defined as radiographic
evidence of a continuous bony connection spanning the two vertebral bodies (i.e., bridging
bone), angular motion on lateral flexion/extension radiographs ≤4°, and evidence of radiolucency
covering more than 50% of either the superior or inferior surface of either graft. For this study,
both treated levels were required to have evidence of fusion in order to claim overall
radiographic fusion success.

Based on those definitions, at 24 months post-operative, 51.0% (100/196) of 2-level Prestige™
LP subjects achieved radiographic success at both treated levels while 82.1% (119/145) of 2­level ACDF control group subjects achieved radiographic success at both treated levels. In
addition, at 120 months post-operative, 47.5% (67/141) of 2-level Prestige™ LP subjects
achieved radiographic success at both treated levels while 93.8% (91/97) of 2-level ACDF
control group subjects achieved radiographic success at both treated levels.

Table 47 presents data on radiographic success at 24 and 120 months by treatment group.

99.6%

99.9%

55.7%

76.7%

94.8%

Medtronic Page 90 of 103

Angular

≤20°

Angular

≤20°

Timepoint

Treatment

Level

Evaluation

INV

CTR

Flexion/extension

angulation (º)

6.75° ± 4.16°

Range: 0.08° - 18.15°

7.12° ± 4.14°

Range: 0.45° - 19.72°

Flexion/extension

translation (mm)

1.48mm ± 1.08mm

Range: 0.13m m – 9.17mm

1.57mm ± 1.14mm

Range: 0.03m m – 8.96mm

Flexion/extension

angulation (º)

5.56° ± 3.89°

Range: 0.37° - 18.20°

5.37° ± 3.26°

Range: 0.37° - 18.51°

Flexion/extension

translation (mm)

1.04mm ± 0.74mm

Range: 0.06m m – 3.42mm

1.14mm ± 0.93mm

Range: 0.0mm – 6.60mm

Flexion/extension

angulation (º)

6.89° ± 4.04°

Range: 0.11° - 20.56°

1.51° ± 1.21°

Range: 0.07° - 8.53°

Flexion/extension

translation (mm)

1.06mm ± 0.67mm

Range: 0.0mm – 3.22mm

0.65mm ± 0.42mm

Range: 0.01m m – 1.85mm

Flexion/extension

angulation (º)

6.70° ± 4.49°

Range: 0.20° - 19.39°

1.70° ± 1.67°

Range: 0.06° - 10.90°

Flexion/extension

translation (mm)

1.02mm ± 0.63mm

Range: 0.0mm – 3.31mm

0.72mm ± 0.53mm

Range: 0.05m m – 3.78mm

Flexion/extension

angulation (º)

6.92° ± 3.96°

Range: 0.21° - 18.89°

1.79° ± 1.33°

Range: 0.09° - 7.51°

Flexion/extension

translation (mm)

1.33mm ± 0.78mm

Range: 0.0mm – 4.05mm

0.81mm ± 0.54mm

Range: 0.03m m – 2.91mm

Flexion/extension

angulation (º)

6.85° ± 4.25°

Range: 0.23° - 21.88°

2.31° ± 2.36°

Range: 0.08° - 18.35°

Flexion/extension

translation (mm)

1.16mm ± 0.71mm

Range: 0.05m m – 4.04mm

0.98mm ± 0.67mm

Range: 0.0mm – 3.49mm

Flexion/extension

angulation (º)

6.64° ± 4.37°

Range: 0.22° - 19.83°

2.35° ± 1.78°

Range: 0.05° - 10.56°

Flexion/extension

translation (mm)

1.42mm ± 0.76mm

Range: 0.00m m – 3.71mm

0.84mm ± 0.56mm

Range: 0.12m m – 3.26mm

Table 47: Radiographic Success at 24 and 120 Months

IDE 24 Months PAS 120 Months

Treatment Level

Superior

Level Only

Inferior Level

INV

Only

Both Treated

Levels

Treatment

Level

Superior

Level Only

Inferior Level

CTR

Only

Both Treated

Levels

Motion

>4° and

141/198
(71.2%)

136/196
(69.4%)

106/197
(53.8%)

Angular

Motion

≤4°

146/153
(95.4%)

127/148
(85.8%)

121/147
(82.3%)

No

Bridging

Bone

184/198
(92.9%)

177/198
(89.4%)

176/198
(88.9%)

Bridging

Bone

154/154

(100%)

149/151
(98.7%)

149/151
(98.7%)

Radiolucency

Not

Applicable

Not

Applicable

Not

Applicable

No

Radiolucency

158/158

(100%)

158/158

(100.0%)

158/158

(100.0%)

Overall

Radiographic

Success

137/197
(69.5%)

126/195
(64.6%)

100/196
(51.0%)

Overall

Radiographic

Success

144/151
(95.4%)

125/146
(85.6%)

119/145
(82.1%)

Motion

>4° and

99/145

(68.3%)

93/140

(66.4%)

73/142

(51.4%)

Angular

Motion ≤4°

103/106
(97.2%)

96/98

(98.0%)

94/98

(95.9%)

No

Bridging

Bone

106/146
(72.6%)

102/143
(71.3%)

90/143

(62.9%)

Bridging

Bone

110/112
(98.2%)

111/112
(99.1%)

109/112
(97.3%)

Radiolucency

Not

Applicable

Not

Applicable

Not

Applicable

No

Radiolucency

113/115
(98.3%)

115/115

(100.0%)

113/115
(98.3%)

Overall

Radiographic

Success

91/144

(63.2%)

83/141

(58.9%)

67/141

(47.5%)

Overall

Radiographic

Success

99/104

(95.2%)

94/96

(97.9%)

91/97

(93.8%)

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

Range of Motion:

Radiographic evaluations of mean range of motion, including angulation and translation (during
flexion and extension), for the treated levels at the pre-operative, 12-month, 24-month, 36­month, 60-month, 84-month, and 120-month timepoints are provided in Table 48.

Table 48: Time course of Radiographic Mean Range of Motion

Superior

Pre-operative

Inferior

Superior

12 Months

Inferior

Superior

24 Months

Inferior

36 Months Superior

Medtronic Page 91 of 103

Timepoint

Treatment

Level

Evaluation

INV

CTR

Flexion/extension

angulation (º)

7.08° ± 4.76°

Range: 0.35° - 24.98°

2.04° ± 1.71°

Range: 0.10° - 8.47°

Flexion/extension

translation (mm)

1.27mm ± 0.79mm

Range: 0.11m m – 4.34mm

1.01mm ± 0.72mm

Range: 0.07m m – 3.46mm

Flexion/extension

angulation (º)

6.32° ± 4.12°

Range: 0.13° - 18.97°

0.77° ± 1.37°

Range: 0.06° - 7.22°

Flexion/extension

translation (mm)

1.09mm ± 0.74mm

Range: 0.00m m – 3.85mm

0.40mm ± 0.36mm

Range: 0.03m m – 1.89mm

Flexion/extension

angulation (º)

6.47° ± 4.66°

Range: 0.10° - 22.37°

0.56° ± 1.15°

Range: 0.02° - 8.47°

Flexion/extension

translation (mm)

0.92mm ± 0.58mm

Range: 0.09m m – 3.19mm

0.47mm ± 0.46mm

Range: 0.0mm – 2.48mm

Flexion/extension

angulation (º)

6.54° ± 4.12°

Range: 0.06° - 17.96°

0.62° ± 0.95°

Range: 0.01° - 4.74°

Flexion/extension

translation (mm)

1.07mm ± 0.73mm

Range: 0.0mm – 3.57mm

0.39mm ± 0.43mm

Range: 0.0mm – 3.00mm

Flexion/extension

angulation (º)

6.27° ± 4.66°

Range: 0.11° -22.52°

0.58° ± 1.24°

Range: 0.02° - 8.47°

Flexion/extension

translation (mm)

0.83mm ± 0.52mm

Range: 0.08mm – 2.34mm

0.35mm ± 0.30mm

Range: 0.00mm – 1.75mm

Flexion/extension

angulation (º)

6.56° ± 4.33°

Range: 0.01° - 16.74°

0.68° ± 1.29°

Range: 0.01° - 8.53°

Flexion/extension

translation (mm)

1.07mm ± 0.79mm

Range: 0.0mm – 3.74mm

0.27mm ± 0.39mm

Range: 0.0mm – 2.44mm

Flexion/extension

angulation (º)

5.90 ° ± 4.28°

Range: 0.05° - 19.43°

0.69° ± 1.77°

Range: 0.01° - 11.56°

Flexion/extension

translation (mm)

0.80mm ± 0.60mm

Range: 0.03m m – 2.48mm

0.35mm ± 0.38mm

Range: 0.01m m – 1.75mm

Inferior

Superior

60 Months

Inferior

Superior

84 Months

Inferior

Superior

120 Months

Inferior

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

The average angular range of motion (flexion/extension) and range of results for all 2-level
Prestige LP™ subjects at the pre-operative, 6 month, 12 month, 24 month, 36 month, 60 month,
84 month, and 120 month timepoints are shown in Figures 3. The points represent the means,
while the bars represent the range between the maximum and minimum at each timepoint.

Medtronic Page 92 of 103

Figure 3: Time Course of Prestige LP™ Cervical Disc Mean Flexion/Extension Range of

Motion at Superior Index Level and at Inferior Index Level

The range of motion values measured from flexion/extension radiographs at 24 months and 120
months for the 2-level Prestige LP™ Cervical Disc subjects are presented in the histograms
below (superior treated level only, inferior treated level only, and combined superior and inferior
treated levels). These histograms use values obtained by rounding the recorded range of motion
for each subject to the nearest integer.

Figure 4: Histogram of Prestige LP™ Cervical Disc Flexion/Extension Angular Range

of Motion at 24 and 120 months (Superior Treated Level Only)

Medtronic Page 93 of 103

Change in Angular

Range of Mot ion

Increased (≥ 2º)

71/193 (36.8%)

2/155 (1.3%)

No Change (-2º to 2º)

58/193 (30.1%)

34/155 (21.9%)

Decreased ≤ -2º)

64/193 (33.2%)

119/155 (76.8%)

Increased (≥ 2º)

77/181 (42.5%)

4/140 (2.9%)

No Change (-2º to 2º)

58/181 (32.0%)

37/140 (26.4%)

Decreased ≤ -2º)

46/181 (25.4%)

99/140 (70.7%)

Figure 5: Histogram of Prestige LP™ Cervical Disc Flexion/Extension Angular

Range of Motion at 24 and 120 months (Inferior Treated Level Only)

Figure 6: Histogram of Prestige LP™ Cervical Disc Flexion/Extension Angular

Range of Motion at 24 months (Combined Superior and Inferior Treated Levels)

Table 49 presents data on change in range of motion from the pre-operative baseline for each

timepoint by treatment group.

Table 49: Timecourse of Radiographic Change in Range of Motion

Timepoint Treatment Level

Superior Level Only

12 Months

Inferior Level Only

Medtronic Page 94 of 103

INV CTR

Increased (≥ 2º)

87/181 (48.1%)

4/140 (2.9%)

No Change (-2º to 2º)

34/181 (18.8%)

13/140 (9.3%)

Decreased ≤ -2º)

60/181 (33.1%)

123/140 (87.9%)

Increased (≥ 2º)

72/190 (37.9%)

1/148 (0.7%)

No Change (-2º to 2º)

56/190 (29.5%)

40/148 (27.0%)

Decreased ≤ -2º)

62/190 (32.6%)

107/148 (72.3%)

Increased (≥ 2º)

77/180 (42.8%)

9/137 (6.6%)

No Change (-2º to 2º)

52/180 (28.9%)

38/137 (27.7%)

Decreased ≤ -2º)

51/180 (28.3%)

90/137 (65.7%)

Increased (≥ 2º)

85/180 (47.2%)

5/137 (3.6%)

No Change (-2º to 2º)

38/180 (21.1%)

17/137 (12.4%)

Decreased ≤ -2º)

57/180 (31.7%)

115/137 (83.9%)

Increased (≥ 2º)

61/175 (34.9%)

4/135 (3.0%)

No Change (-2º to 2º)

44/175 (25.1%)

38/135 (28.1%)

Decreased ≤ -2º)

70/175 (40.0%)

93/135 (68.9%)

Increased (≥ 2º)

76/164 (46.3%)

5/121 (4.1%)

No Change (-2º to 2º)

41/164 (25.0%)

38/121 (31.4%)

Decreased ≤ -2º)

47/164 (28.7%)

78/121 (64.5%)

Increased (≥ 2º)

73/164 (44.5%)

4/121 (3.3%)

No Change (-2º to 2º)

28/164 (17.1%)

12/121 (9.9%)

Decreased ≤ -2º)

63/164 (38.4%)

105/121 (86.8%)

Increased (≥ 2º)

56/158 (35.4%)

0/119 (0.0%)

No Change (-2º to 2º)

45/158 (28.5%)

16/119 (13.4%)

Decreased ≤ -2º)

57/158 (36.1%)

103/119 (86.6%)

Increased (≥ 2º)

60/147 (40.8%)

1/104 (1.0%)

No Change (-2º to 2º)

41/147 (27.9%)

21/104 (20.2%)

Decreased ≤ -2º)

46/147 (31.3%)

82/104 (78.8%)

Increased (≥ 2º)

70/147 (47.6%)

1/104 (1.0%)

No Change (-2º to 2º)

26/147 (17.7%)

1/104 (1.0%)

Decreased ≤ -2º)

51/147 (34.7%)

102/104 (98.1%)

Increased (≥ 2º)

46/146 (32.2%)

1/112 (0.9%)

No Change (-2º to 2º)

47/143 (32.9%)

14/112 (12.5%)

Decreased ≤ -2º)

50/143 (35.0%)

97/112 (86.6%)

Increased (≥ 2º)

60/136 (44.1%)

1/101 (1.0%)

No Change (-2º to 2º)

32/136 (23.5%)

13/101 (12.9%)

Decreased ≤ -2º)

44/136 (32.4%)

87/101 (86.1%)

Increased (≥ 2º)

63/136 (46.3%)

1/101 (1.0%)

No Change (-2º to 2º)

24/136 (17.6%)

2/101 (2.0%)

Decreased ≤ -2º)

49/136 (36.0%)

98/101 (97.0%)

Increased (≥ 2º)

50/140 (35.7%)

0/101 (0.0%)

No Change (-2º to 2º)

33/140 (23.6%)

14/101 (13.9%)

Decreased ≤ -2º)

57/140 (40.7%)

87/101 (86.1%)

Increased (≥ 2º)

56/130 (43.1%)

2/89 (2.2%)

No Change (-2º to 2º)

27/130 (20.8%)

15/89 (16.9%)

Decreased ≤ -2º)

47/130 (36.2%)

72/89 (80.9%)

Increased (≥ 2º)

57/130 (43.8%)

1/89 (1.1%)

No Change (-2º to 2º)

23/130 (17.6%)

2/89 (2.2%)

Decreased ≤ -2º)

50/130 (38.5%)

86/89 (96.6%)

Both Treated Levels

Superior Level Only

24 Months

36 Months

60 Months

84 Months

Inferior Level Only

Both Treated Levels

Superior Level Only

Inferior Level Only

Both Treated Levels

Superior Level Only

Inferior Level Only

Both Treated Levels

Superior Level Only

Inferior Level Only

Both Treated Levels

Superior Level Only

120 Months

Inferior Level Only

Both Treated Levels

Functional Spinal Unit (FSU) Height:

Post-operative measurement of FSU height was considered a surrogate measure of subsidence
due to loss of disc space height. A subject was considered FSU height success if either the
anterior or posterior post-operative FSU height was no more than 2 mm less than the 6 week
post-operative FSU height at both treated levels.

Table 50 presents timecourse data on observed FSU height success rates by treatment group.
FSU height success was similar between the two treatment groups at all timepoints, and FSU
height success rates at 24 months following surgery were 93.5% in the 2-level Prestige LP™
group and 95.7% in the 2-level ACDF control group. FSU height success rates at 120 months
following surgery were 93.3% in the 2-level Prestige LP™ group and 91.6% in the 2-level

Medtronic Page 95 of 103

155/173 (89.6%)

141/149 (94.6%)

158/167 (94.6%)

143/149 (96.0%)

163/171 (95.3%)

129/137 (94.2%)

159/170 (93.5%)

132/138 (95.7%)

146/159 (91.8%)

121/127 (95.3%)

130/140 (92.9%)

109/117 (93.2%)

116/128 (90.6%)

102/110 (92.7%)

112/120 (93.3%)

87/95 (91.6%)

ACDF control group.

Table 50: Time Course of Radiographic Disc Height Success

Timepoint INV CTR

3 Months
6 Months
12 Months
24 Months
36 Months
60 Months
84 Months
120 Months

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

Implant Condition:

In all of the post-operative radiographic reviews, implant condition was assessed for both
treatment groups by independent radiologists. If a plate/screw/graft (control group) or Prestige
LP™ (investigational group) was found to be fractured, bent, broken or had migrated, the
findings were recorded on the study Case Report Forms.

Through 120 months following surgery, one implant in the 2-level ACDF control group was
found to have migrated (at the 12 month visit) and another was found to have broken at the 60
month visit and 120 month visit (same subject). In addition, at the time of PMA application,
there were 3 instances where at least one of the independent radiologists commented on a
radiolucency near a Prestige LP™ device (all at the 24 month visit). Note that these assessments
were not pre-specified and therefore only limited data are available.

Heterotopic Ossification:

Available radiographs for the 2-level Prestige LP™ study subjects were assessed by an
independent radiographic evaluator to determine Heterotopic Ossification (HO) grade (grade 0 to
grade IV) at both the superior and inferior treated levels according to the following grade
definitions established by Mehren:

• Grade 0: No HO present.

• Grade I: HO detectable in front of the vertebral body but not in the anatomic interdiscal

space.

• Grade II: HO growing into the disc space. Possible affection of the function of the prosthesis.

• Grade III: Bridging ossifications which still allow movement of the prosthesis.

• Grade IV: Complete fusion of the treated segment without movement in flexion/extension.

In addition, the independent radiographic evaluator determined the number of subjects with
stable or “worsening” (progressing by at least one grade) HO from visit to visit.

The results are shown in Table 51. The majority of 2-level Prestige LP™ subjects were assessed
as having non-severe HO (grades 0, I, or II). At 24 months post-operative, 14.1% and 16.7% of
2-level Prestige LP™ subjects were assessed as having grade III HO at the superior and inferior
treated levels, respectively. Grade IV HO was present in 2.0% of 2-level Prestige LP™ subjects

Medtronic Page 96 of 103

Grade

Superior Level

Inferior Level

Either Superior

Level

Grade 0

185/202 (91.6%)

173/202 (85.6%)

NA

Grade I

5/202 (2.5%)

14/202 (6.9%)

NA

Grade II

10/202 (5.0%)

9/202 (4.5%)

NA

Grade III

2/202 (1.0%)

6/202 (3.0%)

NA

Grade IV

0/202 (0.0%)

0/202 (0.0%)

0/202 (0.0%)

Grade III/IV

2/202 (1.0%)

6/202 (3.0%)

7/202 (3.5%)

Stable vs. Previous visit

188/201 (93.5%)

176/201 (87.6%)

NA

Worsening vs. Previous visit

13/201 (6.5%)

25/201 (12.4%)

NA

Grade 0

164/202 (81.2%)

151/202 (74.8%)

NA

Grade I

9/202 (4.5%)

11/202 (5.4%)

NA

Grade II

15/202 (7.4%)

18/202 (8.9%)

NA

Grade III

14/202 (6.9%)

21/202 (10.4%)

NA

Grade IV

0/202 (0.0%)

1/202 (0.5%)

1/202 (0.5%)

Grade III/IV

14/202 (6.9%)

22/202 (10.9 %)

27/202 (13.4%)

Stable vs. Previous visit

174/200 (87.0%)

162/199 (81.4%)

NA

Worsening vs. Previous visit

26/200 (13.0%)

37/199 (18.6%)

NA

Grade 0

143/198 (72.2%)

126/198 (63.6%)

NA

Grade I

10/198 (5.1%)

11/198 (5.6%)

NA

Grade II

13/198 (6.6%)

22/198 (11.1%)

NA

Grade III

28/198 (14.1%)

33/198 (16.7%)

NA

Grade IV

4/198 (2.0%)

6/198 (3.0%)

7/198 (3.5%)

Grade III/IV

32/198 (16.1%)

39/198 (19.7%)

48/198 (24.2%)

Stable vs. Previous visit

162/198 (81.8%)

153/197 (77.7%)

NA

Worsening vs. Previous visit

36/198 (18.2%)

44/197 (22.3%)

NA

Grade 0

119/184 (64.7%)

111/184 (60.3%)

NA

Grade I

11/184 (6.0%)

7/184 (3.8%)

NA

Grade II

19/184 (10.3%)

18/184 (9.8%)

NA

Grade III

26/184 (14.1%)

39/184 (21.2%)

NA

Grade IV

9/184 (4.9%)

9/184 (4.9%)

14/184 (7.6%)

Grade III/IV

35/184 (19.0%)

48/184 (26.1%)

59/184 (32.1%)

Stable vs. Previous visit

150/182 (82.4%)

158/182 (86.8%)

NA

Worsening vs. Previous visit

32/182 (17.6%)

24/182 (13.2%)

NA

Grade 0

83/165 (50.3%)

75/165 (45.5%)

NA

Grade I

10/165 (6.1%)

15/165 (9.1%)

NA

Grade II

26/165 (15.8%)

28/165 (17.0%)

NA

Grade III

32/165 (19.4%)

33/165 (20.0%)

NA

Grade IV

14/165 (8.5%)

14/165 (8.5%)

19/165 (11.5%)

Grade III/IV

46/165 (27.9%)

47/165 (28.5%)

64/165 (38.8%)

Stable vs. Previous visit

121/161 (75.2%)

123/161 (76.4%)

NA

Worsening vs. Previous visit

40/161 (24.8%)

38/161 (23.6%)

NA

Grade 0

74/151 (49.0%)

64/151 (42.4%)

NA

Grade I

7/151 (4.6%)

12/151 (7.9%)

NA

Grade II

18/151 (11.9%)

26/151 (17.2%)

NA

Grade III

39/151 (25.8%)

38/151 (25.2%)

NA

Grade IV

13/151 (8.6%)

11/151 (7.3%)

18/151 (11.9%)

Grade III/IV

52/151 (34.4%)

49/151 (32.5%)

64/151 (42.4%)

Stable vs. Previous visit

125/149 (83.9%)

121/148 (81.8%)

NA

Worsening vs. Previous visit

24/149 (16.1%)

27/148 (18.2%)

NA

Grade 0

73/146 (50.0%)

56/146 (38.4%)

NA

Grade I

7/146 (4.8%)

7/146 (4.8%)

NA

at the superior treated level and 3.0% of 2-level Prestige LP™ subjects at the inferior treated
level at 24 months post-operative. The rate of HO of either Grade III or IV at either or both
levels was 24.2% at 24 months postoperative. At 120 months post-operative, 20.5% and 19.9%
of 2-level Prestige LP™ subjects were asses sed as havi ng grade III HO at the superior and
inferior treated levels, respectively. Grade IV HO was present in 8.2% of 2-level Prestige LP™
subjects at the superior treated level and 10.3% of 2-level Prestige LP™ subjects at the inferior
treated level at 120 months post-operative. The rate of HO of either Grade III or IV at either or
both levels was 39.0% at 10 years postoperative, not an increase from 7 years (42.4%).

Table 51: Timecourse of Heterotopic Ossification (HO)

Level/Inferior

6 Months

12 Months

24 Months

36 Months

60 Months

84 Months

120 Months

Medtronic Page 97 of 103

Grade

Superior Level

Inferior Level

Either Superior

Level

Grade II

24/146 (16.4%)

39/146 (26.7%)

NA

Grade III

30/146 (20.5%)

29/146 (19.9%)

NA

Grade IV

12/146 (8.2%)

15/146 (10.3%)

19/146 (13.0%)

Grade III/IV

42/146 (28.7%)

44/146 (30.2%)

57/146 (39.0%)

Stable vs. Previous visit

125/139 (89.9%)

109/135 (80.7%)

NA

Worsening vs. Previous visit

14/139 (10.1%)

26/135 (19.3%)

NA

Level/Inferior

Available radiographs for the 2-level Prestige LP™ study subjects were also assessed for
bridging bone (Criteria was comparable to grade IV assessment on the McAfee and Mehren
classification system for Heterotopic Ossification) between the vertebral bodies of the implanted
motion segment. Bridging was defined as evidence of a continuous bony connection from the
superior vertebral body to the inferior vertebral body laterally, anteriorly, and/or posteriorly.
At 24 months post-operatively, 88.9% (176/198) of the subjects treated with the 2-level Prestige
LP™ exhibited no bridging bone at either treatment level, whereas 11.1% (22/198) exhibited
bridging bone at one or both treatment levels [7.1% (14/198) at the superior treated level and

10.6% (21/198) at the inferior treated level]. At 120 months post-operatively, 62.9% (90/143) of
the subjects treated with the 2-level Prestige LP™ exhibited no bridging bone at either treatment
level, whereas 37.1% (53/143) exhibited bridging bone at one or both treatment levels [27.4%
(40/146) at the superior treated level and 28.7% (41/143) at the inferior treated level]. Even
though grade IV HO and bridging bone assessments are interrelated, the results are similar but
not identical because the assessment methods were different and independent.

Demographic and baseline characteristics were evaluated for potential correlation with HO
grade, and no correlation was found. In addition, to assess the effect of HO on clinical outcomes,
the applicant evaluated overall success (and component) outcomes as well as NDI outcomes and
arm and neck pain outcomes in subjects with non-severe HO (defined as grades 0, I, and II) and
in subjects with severe HO (defined as grades III and IV). No clinically meaningful correlation
was found.

Adjacent Level Treatments:
Some subjects went on to receive post-operative treatment at adjacent level(s). The incidence and
progression of adjacent level disease was not collected prospectively, but was assessed in terms
of symptoms, treatment, and surgery performed at adjacent level(s) by a thorough review of
adverse event source documentation for adverse events coded as pain (neck and/or upper
extremity), dysesthesia (neck and/or upper extremity), neurological, weakness, muscle spasms,
surgery, pseudoarthrosis, or headache to isolate possible adjacent level symptoms, diagnoses,
treatments, and surgeries.

Based on this review, the percentage of subjects who underwent surgery at adjacent level(s)
(including those who had combined subsequent surgery at the index and adjacent level(s)) was

7.7% (16 subjects, 16 events) for the 2-level Prestige LP™ group and 12.8% (24 subjects, 34
events) for the 2-level ACDF control group. The types of adjacent level procedures that were
performed are summarized in Table 52. The percentages are based on the number of subjects
experiencing a particular type of adjacent level surgery divided by the total number of subjects in
each group. For the row of “total”, the percentage is based on the number of subjects who
experienced any type of adjacent level surgeries divided by the total number of subjects in each
group.

Medtronic Page 98 of 103

Adjacent Level Treat ment

INV

CTR

#Events

# Subject (%)

# Events

# Subject (%)

Adjacent level fusion-1 level

10

10 (4.8%)

9

9 (4.8%)

Adjacent level fusion- 2 level

2

2 (1.0%)

3

3 (1.6%)

Adjacent level fusion- 3 level

0

0 (0%)

1

1 (0.5%)

Adjacent level decompression- 1 Level

7

7 (3.0%)

10

10 (5.3%)

Adjacent level decompression- 2 Level

1

1 (0.5%)

7

7 (3.7%)

Bone Growth Stimulator

0

0 (0.0%)

1

1 (0.5%)

Cervical Total Disc Replacement- 1 Level

1

1 (0.5%)

4

4 (2.1%)

Cervical Total Disc Replacement- 2 Level

1

1 (0.5%)

2

2 (1%)

Cervical wound exploration and repair of dural t ear and CSF leak

0

0 (0.0%)

1

1 (0.5%)

Rhizotomy

1

1 (0.5%)

0

0 (0.0%)

Total

16

16 (7.7%)

34

24 (12.8%)

INV

CTR

Pre-operative

Non-Narcotic Medica t io ns

138/208 (66.4%)

133/185 (71.9%)

Weak Narco t ic Medications*

83/208 (39.9%)

78/186 (41.9%)

Strong Narcot ic Medications**

52/207 (25.1%)

44/188 (23.4%)

Muscle Relaxant Med ic ati o ns

75/208 (36.0%)

73/188 (38.8%)

24 Months

Non-Narcotic Medica t io ns

85/199 (42.8%)

63/157 (40.2%)

Weak Narco t ic Medications*

25/197 (12.7%)

30/157 (19.2%)

Strong Narcot ic Medications**

15/196 (7.7%)

16/158 (10.1%)

Muscle Relaxant Med ic ati o ns

35/197 (17.7%)

36/157 (22.9%)

120 Months

Non-Narcotic Medica t io ns

51/147 (34.7%)

50/113 (44.3%)

Weak Narco t ic Medications*

12/146 (8.2%)

16/112 (14.4%)

Strong Narcotic Medications**

10/146 (6.9%)

13/113 (11.5%)

Muscle Relaxant Med ic ati o ns

20/144 (14.0%)

15/113 (13.3%)

Table 52: Types of Adjacent Level Treatments

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

Decompression includes foraminotomy, laminotomy, laminoplasty, corpectomy, osteophytectomy, micorforaminotomy, laminoforaminotomy,
hemilaminectom y, an d lam inectomy

Most surgical interventions required more than one treatment type.

Pain Management:
Table 53 presents data on pain and muscle relaxant medication use at baseline pre-operative, at
24 months, and at 120 months post-operative by treatment group. Use of pain medication was
similar in all treatment groups. For subjects on medication, the frequency of medication use
ranged from once a week to three or more times a day.

Table 53: Pain and Muscle Relaxant Medication Usage Pre-operative, 24 Months, and

120 Months Post-operative

*Weak narcotic medications include such examples as Tylenol #3, Darvocet N-100, Darvon, and Vicodin.

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

** Strong narcotic medications include such examples as Percodan, Percocet, Morphine, and Demerol.

Some subjects required additional non-surgical procedures at one or both of the index levels,
subsequent to the initial surgery. Through all available follow-up, there were 136 additional
procedures at the index level(s) in 63 (30.1%) 2-level Prestige LP™ subjects and 172 additional
procedures at the index level(s) in 57 (30.3%) 2-level ACDF control subjects. The timecourse of
the additional procedures through all available follow-up is summarized in Table 54.

Medtronic Page 99 of 103

Procedure

INV

CTR

Facet Injection

5 /209 (2.4%)

8/188 (4.3%)

Medial Branch Block

0/209 (0.0%)

3/188 (1.6%)

Selective Nerve Root Bl oc k

4/209 (1.9%)

4/188 (2.1%)

Series of Epidural Steroid Injections

10/209 (4.8%)

7/188 (3.7%)

Single Epidur al Steroid Injection

23/209 (11.0%)

21/188 (11.2%)

Steroid Injection

23/209 (11.0%)

31/188 (16.5%)

Sympathetic Block (Including Ganglion)

0/209 (0.0%)

1/188 (0.5%)

Trial Spinal Cord Stimulator

2/209 (1.0%)

2/188 (1.1%)

Trigger Point Injection

3/209 (1.4%)

10/188 (5.3%)

Other

24/209 (11.5%)

20/188 (10.6%)

Total

63/209 (30.1%)

57/188 (30.3%)

Table 54: Additional Non-Surgical Procedures at the Index Level(s) Through All

Available Follow-up Classified by Procedure Type

INV=2-level Prestige LP™ (N=209); CTR = 2-level ACDF control (N=188)

Study Strength and Limitations

The following are important study design strengths of the IDE study as well as the post-approval
study:
▪ The PAS provided extended term profile of safety and effectiveness as well as functional data
established on a multicenter, randomized, controlled clinical trial.
▪ The consistency of data gathering approaches and endpoints was maintained through both the
IDE and the PAS studies.
▪ The strength and reliability of the final IDE and PAS conclusions were confirmed by several
sensitivity analyses.
▪ The study design minimized potential biases by integrating a wide variety of assessments
including subjective data, physician-judged and core laboratory-assessed evaluations.

The following potential study design limitations should also be considered when interpreting the
results of the IDE study as well as the post-approval study:
▪ Although overall success data was available for 85-86% of all the subjects expected at 120
months, due to the long-term nature of the IDE and the post-approval studies, some subjects
were lost to follow-ups because some sites stopped participating in the PAS study, which may
affect interpretation of long-term study results.
▪ Several of the primary and secondary study endpoints are subjective (e.g., NDI, pain scores,
SF-36), and this subjectivity may present biases.
▪ The capability to evaluate device performance for individual segments of the subject population
is limited. This limitation is mainly because the study was not designed to assess performance
among subgroups. Any subgroup analyses should be evaluated with caution.

Conclusions Drawn from the Study Data

The clinical data support the reasonable assurance of safety and effectiveness of the Prestige
LP™ Cervical Disc when used in accordance with the indications for use. Based on the clinical
study results, it is reasonable to conclude that a significant portion of the indicated patient
population will achieve clinically significant results and that the clinical benefits of the use of the
Prestige LP™ Cervical Disc at two contiguous levels in terms of improvement in pain and

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