MOBI-C CERVICAL DISC PROSTHESIS (ONE-LEVEL INDICATION)

{0} SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) I. GENERAL INFORMATION Device Generic Name: Artificial Cervical Disc Device Trade Name: Mobi-C® Cervical Disc Prosthesis Device Procode: MJO Applicant's Name and Address: LDR Spine USA, Inc. 13785 Research Boulevard, Suite 200 Austin, TX 78750 USA Date of Panel Recommendation: None Premarket Approval Application (PMA) Number: P110002 Date of FDA Notice of Approval: August 7, 2013 Expedited: Not Applicable II. INDICATIONS FOR USE The Mobi-C® Cervical Disc Prosthesis is indicated in skeletally mature patients for reconstruction of the disc at one level from C3-C7 following single-level discectomy for intractable radiculopathy (arm pain and/or a neurological deficit) with or without neck pain, or myelopathy due to a single-level abnormality localized to the level of the disc space and at least one of the following conditions confirmed by radiographic imaging (CT, MRI, X-rays): herniated nucleus pulposus, spondylosis (defined by the presence of osteophytes), and/or visible loss of disc height compared to adjacent levels. The Mobi-C® Cervical Disc Prosthesis is implanted using an anterior approach. Patients should have failed at least 6 weeks of conservative treatment or demonstrated progressive signs or symptoms despite nonoperative treatment prior to implantation of the Mobi-C® Cervical Disc Prosthesis. III. CONTRAINDICATIONS The Mobi-C® Cervical Disc Prosthesis should not be implanted in patients with the following conditions: - Acute or chronic infection, systemic or at the operative site; - Known allergy or sensitivity to the implant materials (cobalt, chromium, molybdenum, titanium, hydroxyapatite, or polyethylene); LDR Spine -Mobi-C® P110002 Page 1 of 76 {1} - Compromised vertebral bodies at the index level due to previous trauma to the cervical spine or to significant cervical anatomical deformity or disease (e.g., ankylosing spondylitis, rheumatoid arthritis); - Marked cervical instability on resting lateral or flexion/extension radiographs demonstrated by translation greater than $3.5\mathrm{mm}$ , and/or $>11^{\circ}$ angular difference to that of either adjacent level. - Osteoporosis or osteopenia defined as DEXA bone mineral density T-score $< -1.5$ - Severe facet joint disease or degeneration. # IV.WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the Mobi-C® Cervical Disc Prosthesis labeling. # V.DEVICE DESCRIPTION The Mobi-C® is a weight-bearing, articulating interbody implant comprised of an ultra-high-molecular-weight polyethylene (UHMWPE per ISO 5834-2) mobile insert sandwiched between two spinal plates consisting of cobalt, chromium, molybdenum (CoCrMo per ISO 5832-12) alloy with a titanium (per ASTM F1580) and hydroxyapatite (per ISO 13779) plasma spray coating. Multiple vertebral body footprint sizes and mobile insert heights are available to conform to the individual patient's anatomy. The components are pre-assembled to create a range of implant configurations. Illustrations of the device are provided below. A set of instruments suitable for cervical spinal interbody surgery, are needed for implantation.  Figure 1. Assembled Mobi-C® (Posterior and Anterior Views) # A. Device Components The Mobi-C® endplates consist of CoCrMo alloy with a titanium and hydroxyapatite plasma spray coating. Both the superior and inferior spinal endplates incorporate two rows of serrated teeth that are located laterally on each plate. The teeth sink into the bone to facilitate endplate fixation and do not require any bone removal or chiseling prior to insertion. The Mobi-C has a bone sparing design and technique. The inner surfaces of the LDR Spine -Mobi-C® P110002 {2} endplates that contact the mobile insert feature highly polished surfaces to permit articulation on the mobile insert while enabling a limited amount (approximately $1\mathrm{mm}$ ) of translation in the X-Y plane for the mobile insert within the endplates. The Mobi-C® endplates are available in seven footprint sizes to address individual patient anatomy and maximize endplate coverage. These sizes are illustrated in the table below. Table 1. Mobi-C® Device Configurations | Depth x Width (mm) | Inferior/Superior Plate & Mobile Insert Sizes Combinations | | | | | | | Height (mm) | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Endplates | 13 x 15 | 14 x 15 | 15 x 15 | 13 x 17 | 14 x 17 | 15 x 17 | 15 x 19 | H5H6H7 | | Mobile Insert | 11 x 12 | 11 x 12 | 11 x 12 | 11 x 12 | 11 x 12 | 13 x 14 | 13 x 14 | | | Product Scope | | | | | | | | | | Part Number | | | Footprint (mm) | | | Height (mm) | | | | MB 3355 | | | 13×15 | | | H5 | | | | MB 3356 | | | 13×15 | | | H6 | | | | MB 3357 | | | 13×15 | | | H7 | | | | MB 3455 | | | 14×15 | | | H5 | | | | MB 3456 | | | 14×15 | | | H6 | | | | MB 3457 | | | 14×15 | | | H7 | | | | MB 3555 | | | 15×15 | | | H5 | | | | MB 3556 | | | 15×15 | | | H6 | | | | MB 3557 | | | 15×15 | | | H7 | | | | MB 3375 | | | 13×17 | | | H5 | | | | MB 3376 | | | 13×17 | | | H6 | | | | MB 3377 | | | 13×17 | | | H7 | | | | MB 3475 | | | 14×17 | | | H5 | | | | MB 3476 | | | 14×17 | | | H6 | | | | MB 3477 | | | 14×17 | | | H7 | | | | MB 3575 | | | 15×17 | | | H5 | | | | MB 3576 | | | 15×17 | | | H6 | | | | MB 3577 | | | 15×17 | | | H7 | | | | MB 3595 | | | 15×19 | | | H5 | | | | MB 3596 | | | 15×19 | | | H6 | | | | MB 3597 | | | 15×19 | | | H7 | | | The Mobi-C® UHMWPE mobile insert consists of a standard (symmetric) convex spherical dome that is radiolucent. The mobile insert articulates with both the superior and inferior device endplates, the inner contact surfaces of which are spherical and flat, respectively. The bottom of the mobile insert contains a grooved feature to enhance lubrication of the mobile insert and inferior endplate surfaces with bodily fluids. The mobile insert is self-centering on the inferior endplate. Each movement of the superior plate induces the mobile insert to re-position on the inferior spinal plate, which maintains the superior versus inferior vertebral alignment. The mobile insert is available in three different heights that result in a total prosthesis height of $5\mathrm{mm}$ (H5), $6\mathrm{mm}$ (H6) or $7\mathrm{mm}$ (H7), to better accommodate individual patient anatomy. In LDR Spine -Mobi-C® P110002 {3} addition, each of the three insert heights is available in two different footprints to accommodate the range of device endplate sizes. The purpose of the Mobi-C® device is to provide pain relief and restore normal biomechanical function to a diseased spine level after disc excision. The mobile insert articulates between the superior and inferior spinal plates, which allows for multiaxial motion, including five independent degrees of freedom that include two translational and three rotational. The five independent degrees of freedom are illustrated below. The kinematic principle behind the Mobi-C® design is to allow for normal range of motion in the cervical spine and to enable or re-establish the physiological mobility of the targeted disc space through the mobile insert design. This biomechanical and kinematic concept (the mobile insert design) is designed to preserve the instantaneous axis of rotation of the affected disc space.  Figure 2. Degrees of Freedom of the Mobi-C® The inferior endplate includes two lateral stops that control and limit the translation and rotation of the mobile insert. The lateral stops also prevent the potential for migration of the mobile insert. Mobi-C® is designed to control the amount of translation by the mobile insert in the X and Y plane to $\pm 1\mathrm{mm}$ . The device is also designed to allow for $\pm 8^{\circ}$ of mobile insert rotation about the Z axis. The superior endplate is unconstrained in Z axis rotation. Rotation in flexion/extension about the Y axis is designed to be at least $\pm 10^{\circ}$ , while rotation in lateral bending about the X axis is also designed to be at least $\pm 10^{\circ}$ . This combination of controlled mobility allows the mobile insert to be self-centering on the inferior plate. Each movement of the superior plate induces the mobile insert to re-position on the inferior plate which maintains the superior versus inferior vertebral alignment. For the product scope, these design parameters are met. # VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several other alternatives for the treatment of intractable radiculopathy or myelopathy due to a single-level abnormality localized to the level of the disc space. - Nonoperative alternative treatments include, but are not limited to, physical therapy, medications, braces, chiropractic care, bed rest, spinal injections, or exercise programs. LDR Spine -Mobi-C® P110002 {4} - Surgical alternatives include, but are not limited to, surgical decompression and/or fusion using various bone grafting techniques or interbody fusion devices, which may or may not be used in conjunction with anterior cervical plating (e.g., plate and screws), or posterior spinal systems (e.g., rods, hooks, wires). Anterior cervical discectomy and fusion (ACDF) with an interbody graft or spacer is the most commonly used method for decompression and fusion. Intractable radiculopathy or myelopathy due to a single-level abnormality localized to the disc space may also be treated surgically using another FDA approved artificial cervical disc¹. Each alternative has advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician. ## VII. MARKETING HISTORY The Mobi-C® received CE Mark approval in 2004 and is currently distributed in 24 countries in Europe, Africa, Asia, Australia, and the Americas. The device has not been withdrawn from the market for any reason relating to safety and effectiveness. The Mobi-C® is available in: Argentina, Australia, Austria, Belgium, Brazil, China, Denmark, France, Germany, Greece, Italy, Korea, Malaysia, Mexico, Portugal, Singapore, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, and Venezuela. ## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (e.g., complications) identified from the Mobi-C® Cervical Disc Prosthesis 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 Mobi-C® Cervical Disc Prosthesis. 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: abscess; cellulitis; wound dehiscence; wound, local, and/or systemic infection; wound necrosis; edema; hematoma; heart and vascular complications; hypertension; thrombosis; ischemia; embolism; thromboembolism; hemorrhage; thrombophlebitis; adverse reactions to anesthesia; pulmonary complications; organ, nerve or muscular damage; gastrointestinal or genitourinary compromise; seizure, convulsion, or changes to mental status; complications of pregnancy including miscarriage and fetal birth defects; inability to resume activities of daily living; and death. 2. Risks associated with anterior cervical spine surgery include: dysphagia; dysphonia; hoarseness; vocal cord paralysis; laryngeal palsy; sore throat; recurring aspirations; tracheal, esophageal, or pharyngeal perforation; airway obstruction; warmth or tingling in the extremities; neurologic complications including damage to nerve roots, other nerves or the spinal cord, possibly resulting in weakness, pain or even paralysis; dural tears or leak; cerebrospinal fistula; discitis, arachnoiditis, and other types of inflammation; loss of disc LDR Spine – Mobi-C® P110002 Page 5 of 76 {5} height; loss of anatomic sagittal plane curvature, vertebral listhesis; scarring, herniation or degeneration of adjacent discs; surrounding soft tissue damage, spinal stenosis; spondylolysis; fistula; vascular damage and/or rupture; and headache. 3. Risks associated with a cervical artificial disc device, including the Mobi-C® Cervical Disc Prosthesis, include: early or late loosening of the components; disassembly; bending or breakage of any or all of the components; implant migration; implant malpositioning; implant subsidence; loss of fixation; sizing issues with components; anatomical or technical difficulties; bone fracture; possible tissue reaction; metallosis, and/or scarring; bone resorption; bone formation (including heterotopic ossification) that may reduce spinal motion or result in a fusion, either at the treated level or at adjacent levels; development of new radiculopathy, myelopathy, or pain; tissue or nerve damage caused by improper positioning or placement of implants or instruments; bending or breakage of a surgical instrument; loss of neurological function; decreased strength of extremities; decreased reflexes; cord or nerve root injury; interference with radiographic imaging because of the presence of the implant; and the need for subsequent surgical intervention. For the specific adverse events that occurred in the clinical study of the Mobi-C® Cervical Disc Prosthesis, please see Section X below. ## IX. SUMMARY OF PRECLINICAL STUDIES A variety of testing was conducted to characterize the performance of the Mobi-C® Cervical Disc Prosthesis, as follows: ### A. Laboratory Studies - Static and Dynamic Axial Compression Testing - Static and Dynamic Shear Compression Testing - Creep and Stress Relaxation Testing - Static Expulsion Testing – Full Device - Static Expulsion Testing – Mobile Insert Only - Subsidence Testing - Subluxation Testing - Durability and Wear Testing - Wear Particulate Analysis ### B. Animal Studies None ### C. Additional Studies - Sterilization, Packaging, and Shelf Life Testing - Biocompatibility - Instrument Testing Table 3. Summary of Laboratory Studies LDR Spine – Mobi-C® P110002 Page 6 of 76 {6} LDR Spine –Mobi-C® P110002 Page 7 of 76 | Test Name | Purpose | Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | **Static Axial Compression** | To evaluate the performance of the Mobi-C® device under static axial compressive loading. | Six (6) Mobi-C® specimens were tested under static compression in ambient air at a rate of 0.2mm/sec until failure. | Static axial compression testing must demonstrate that the device can withstand the maximum axial load that a cervical intervertebral disc can withstand (75N²). | The mean yield load was 1934.98 ± 108.771 N, and mean yield displacement = 0.44 ± 0.03 mm. These results suggest that the Mobi-C® can withstand compressive loading that exceeds the anticipated physiologic loads on the cervical spine. | | **Dynamic Axial Compression** | To evaluate the performance of the Mobi-C® device under dynamic axial compressive loading. | Six (6) Mobi-C® specimens were tested under dynamic compression in phosphate buffered solution (“PBS”) at 37 ± 3° C to 10 million cycles, using a sinusoidal wave form with R=10 at 5Hz and 2 Hz until 10 million cycles or gross deformation/ failure. | Dynamic axial compression testing must demonstrate that the device can withstand the maximum axial load that a cervical intervertebral disc can withstand (75N²). | Specimens demonstrated endurance limit of at least 1125N. These results suggest that the Mobi-C® can withstand dynamic compressive loading that exceeds the anticipated physiologic loads on the cervical spine. | | **Static Compression-Shear** | To evaluate the performance of the Mobi-C® device under static compression-shear. | Six (6) Mobi-C® specimens were tested under static compression-shear (45° angle) in ambient air at a rate of 0.2mm/sec until failure. | Static shear compression testing must demonstrate that the device can withstand the maximum shear load that a cervical intervertebral disc can withstand (20N²). | The mean 2% yield of the samples tested demonstrated that the device withstood 454.36 (114.6N) at mean displacement of 0.41mm of displacement. These results suggest that the Mobi-C® can withstand compressive shear loading that exceeds the anticipated physiologic loads on the cervical spine. | {7} LDR Spine –Mobi-C® P110002 Page 8 of 76 | Dynamic Compression-Shear | To evaluate the performance of the Mobi-C® device under dynamic compressive-shear loading. | Six (6) Mobi-C® specimens were tested under dynamic compression shear in phosphate buffered solution (“PBS”) at 37 ± 3°C to 10 million cycles, using a sinusoidal wave form with R=10 at 5Hz and 2 Hz until 10 million cycles or gross deformation/failure. | Dynamic shear compression testing must demonstrate that the device can withstand the maximum shear load that a cervical intervertebral disc can withstand (20N²). | The two specimens tested at applied load of 450 N ran out to 10 million cycles with no observed failure. These results suggest that the Mobi-C® can withstand dynamic compressive shear loading that exceeds the anticipated physiologic loads on the cervical spine. | | --- | --- | --- | --- | --- | | Creep Characterization | To evaluate the creep characteristics of the Mobi-C® device. | Twelve (12) Mobi-C® specimens were tested under static compression in 37 ± 3°C phosphate buffered solution (“PBS”). A maximum load was applied for 24 hours and a minimum load was applied for 24 hours. Creep was evaluated at 3600N, 4800N, 6000N, & 7200N. | Test was performed for characterization only. | Specimens tested at loads in excess of 3x the dynamic axial fatigue limit demonstrated permanent height loss of less than 0.8mm. These results suggest that the height loss of the Mobi-C® occurs at loads far in excess of in anticipated in vivo loads (and beyond failure load of native anatomy). | | Static Expulsion of Full Device | To evaluate the loads required to expulse the Mobi-C® device. | Six (6) Mobi-C® specimens with axial preload of 100N were tested in rigid polyurethane foam blocks to determine the amount of force required to displace the device from simulated bone. Devices loaded at 0.1mm/sec in ambient air. Tests were conducted in displacement control at a rate of 6mm/min | Device must withstand the shear failure load of the cervical intervertebral disc (20N²) without expulsion. | The mean peak expulsion load was 142N ±18N at 0.93mm ±0.64mm of displacement. These results suggest that the Mobi-C® can resist pushout forces that exceed the anticipated physiologic loads on the cervical spine. | {8} LDR Spine –Mobi-C® P110002 Page 9 of 76 | Static Expulsion of Device Mobile Core Only | To evaluate the loads required to expulse the Mobi-C® mobile insert from the adjacent endplates. | Six (6) Mobi-C® specimens with axial preload of 100N and tested to determine the amount of force required to displace the core from the endplates by at least 3mm. Devices loaded at 0.1mm/sec in ambient air. Tests were conducted in displacement control at a rate of 6mm/min. | Mobile core must withstand the shear failure load of the cervical intervertebral disc (20N²) without expulsion. | Expulsion force of 496.64 N under the worst-case scenario of a force applied directly to the polyethylene inlay at 3.00 mm displacement exceeded the shear failure load. These results suggest that the Mobi-C® can resist disassembly at loads that exceed anticipated physiologic loads on the cervical spine. | | --- | --- | --- | --- | --- | | Subsidence | To evaluate the Mobi-C® implant’s resistance to subsidence into the vertebral endplate. | Six (6) Mobi-C® specimens were inserted into rigid polyurethane blocks simulating cancellous bone and loaded in compression at a rate of 0.1mm/sec in ambient air until 6mm of displacement was reached. | Subsidence testing must demonstrate that the device can withstand loads greater than maximum axial load that a cervical intervertebral disc can withstand (75N²). | The average displacement at the offset load of 1039N ±25N was 3.12mm ±0.25mm. These results suggest that the Mobi-C® can resist subsidence loads that exceed anticipated physiologic loads on the cervical spine. | {9} | Subluxation | To characterize the shear force necessary to cause subluxation of the superior endplate relative to the mobile insert. | 48 total Mobi-C® specimens were tested (6 for each test configuration, 3 of each height) in deionized water in neutral, flexion/extension, and lateral bending configurations. Superior endplates were mounted and attached to a rigid superior fixtures and the inferior endplate was mounted to an actuator that applied shear force at 0.1667 mm/sec. Axial vertical preload of 100N was placed on superior test block. Mobile insert was placed between the endplates. | Peak shear force to produce subluxation was required to exceed the shear load that a natural cervical disc can withstand (20 N²). | All specimens experienced subluxation of the superior endplate from the polyethylene inlay with no observed failure to the inlay and no deformation or damage observed to the metal endplates (peak shear force applied exceeded load that natural disc can withstand). The worst case configuration experienced subluxation at 22.2±0.28N of shear load. These results suggest that the Mobi-C® can resist subluxation loads that exceed anticipated physiologic loads on the cervical spine. | | --- | --- | --- | --- | --- | LDR Spine -Mobi-C® P110002 Page 10 of 76 {10} LDR Spine –Mobi-C® P110002 Page 11 of 76 | Wear Testing | To determine the wear and durability characteristics of the Mobi-C® device under complex physiologic conditions. | Six (6) Mobi-C® specimens were tested under the ISO 18192-1 (2011) standard with two (2) loaded soak controls: **Coupled Motion** Combined flexion/extension (± 7.5°), lateral bending (± 6°) and rotation (± 4°) under axial compression (50-150N), for 10 million cycles at a frequency of 1Hz. **Controls** Controls were subjected to the axial compression load only. **Wear Particulate Analysis** Collected wear debris at 500,000 and at each 1 million cycle interval above were analyzed via electron microscopy and low angle laser light scattering under ASTM F1877-05. All specimens were placed in a 37 ± 3°C de-ionized water test medium and bovine serum. Specimens were weighed, measured, and the solution was collected at each cycle check. | The device was required to demonstrate wear data and particulate analysis consistent with what has been for other cervical discs made of the same materials (2.59±0.36mg / million cycles). | Wear Testing The mean gravimetric wear rate over the 10 million cycles was 1.546 ±0.075mg/million-cycles. Controls demonstrated negligible wear. There were no mechanical failures or damage to tested components. Wear Particulate Analysis Wear particles were polymeric, consistent with wear of the polyethylene component, and free of metal wear particles. Average particle size for all samples was 0.77 μm (SEM) and an aspect ratio of 2.15. Conclusion The wear rate and the volume and size of the particulate wear debris are similar to other legally-marketed total disc replacements featuring the same materials and similar surface geometry. | | --- | --- | --- | --- | --- | {11} | Impingement Wear Testing | To determine the wear and durability characteristics of the Mobi-C® device under conditions simulating device impingement. | Six (6) Mobi-C® specimens were tested with two (2) loaded soak controls. Each Mobi-C® specimen underwent 1 million cycles of ISO 18192-1 wear testing followed by an additional 1 million cycles simulating impingement conditions. Custom test fixtures placed the device in excessive angulation at neutral and specimens were mechanically deformed prior to testing in order to achieve the impingement conditions. Solely flexion/extension motion was applied to maximize impingement. | Test was performed for characterization only. | The 1 million cycles of ISO wear yielded 1.53 ± 0.30mg/million-cycles, similar to the results of the 10 million cycle ISO wear study (1.546 ±0.075mg/million-cycles). The mean gravimetric wear rate over the 1 million cycles of impingement testing was negligible for the polyethylene insert. For the endplates, the wear rate (mg/MC) averaged 0.23 ± 0.20 for the superior endplate and 0.87 ± 1.1 for the inferior endplate. There were no mechanical failures. | | --- | --- | --- | --- | --- | White AA, Panjabi MM. Clinical Biomechanics of the Spine. Philadelphia: Lippincott, Williams & Wilkins. 1990. Page 9 ## B. Additional Studies ## Sterilization, Packaging, and Shelf Life Testing The Mobi-C® device is provided pre-assembled in a sterile package ready for use. All Mobi-C® components are sterilized using gamma radiation at a minimum dose of 25 kGy, at a sterilization assurance level (SAL) of 10⁻⁶. Sterilization validation according to ANSI/AAMI/ISO 11137-2: 2006 was conducted to confirm that the sterility assurance level of the device is maintained through a sterile barrier. The device is provided sterile in a double barrier system to allow for easy transfer to the sterile field, with a shelf life of 5 years. The general purpose instruments used to implant the Mobi-C® are provided non-sterile for sterilization by the user. Validation of the recommended sterilization cycle was conducted on the worst case instrument set. LDR Spine –Mobi-C® P110002 Page 12 of 76 {12} LDR Spine –Mobi-C® P110002 Page 13 of 76 ## Biocompatibility The components of the Mobi-C® are constructed of Cobalt, Chromium, Molybdenum (CoCrMo) alloy with Titanium (per ASTM F1580) and hydroxyapatite (per ISO 13779) plasma spray coating and Ultra High Molecular Weight Polyethylene (UHMWPE). The CoCrMo alloy conforms to ISO 5832-12 Alloy. The UHMWPE conforms to ISO 5834-2. All these materials have a long history of use in medical implants with no significant biocompatibility issues, as shown in the literature. ## Instrument Testing Implantation of the Mobi-C® requires a set of instruments suitable for cervical spinal interbody surgery. These instruments are made of materials that have a long history of use in contact with human tissue and fluids. Validation testing was conducted with the instruments, including cleaning, steam sterilization (according to ISO 17665-1:2006), and simulated surgery on cadaveric segments performed by designing surgeons. ## X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of reconstruction of the disc with the Mobi-C® Cervical Disc Prosthesis at one level from C3-C7 following single-level discectomy for treatment of intractable radiculopathy (arm pain and/or a neurological deficit) with or without neck pain or myelopathy due to a single-level abnormality localized to the level of the disc space and at least one of the following conditions confirmed by radiographic imaging (CT, MRI, X-rays): herniated nucleus pulposus, spondylosis (defined by the presence of osteophytes), and/or visible loss of disc height compared to adjacent levels in skeletally mature patients without prior cervical fusion. The study was performed in the United States under IDE # G050212. This IDE study consisted of one-level and two-level treatment arms conducted simultaneously under the same FDA-approved protocol. The basis for this summary is data from the first arm of the two arm study consisting of treatment with the Mobi-C® Cervical Disc Prosthesis at a single level. Data from this single level clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below. ### A. Study Design Patients were treated between April 2006 and March 2008. The database for this PMA reflected data collected through August 2011 and included 271 patients (260 patients with surgery). There were 24 investigational sites. The study was a prospective, multi-center, two-arm, randomized (2:1), unmasked, concurrently controlled, non-inferiority clinical study to compare the safety and effectiveness of the Mobi-C® Cervical Disc Prosthesis to the standard of care (a legally marketed alternative with similar indications for use), anterior cervical discectomy and fusion (ACDF) using a semi-constrained, rotational anterior cervical plate (Depuy Spine SLIM-LOC™ Anterior Cervical Plate System; Medtronic Sofamor Danek ATLANTIS™ or ATLANTIS™ VISION Anterior Cervical Plate System) and structural corticocancellous allograft bone (frozen or freeze-dried, must be obtained from an American Association of Tissue Banks (AATB) accredited bone bank) in {13} treating patients with degenerative disc disease (DDD) with radiculopathy or myeloradiculopathy at one level between C3 and C7. The first subject enrolled at each center was a non-randomized subject (i.e. training case) receiving the Mobi-C® Cervical Disc Prosthesis in order for the staff to become familiar with the implantation procedure for the device. As the IDE study consisted of one-level and two-level treatment arms conducted simultaneously under the same FDA-approved protocol, some centers enrolled a one-level subject first and conducted a one-level non-randomized training case (n=15), while other centers enrolled a two-level subject first and conducted a two-level non-randomized training case (n=9). All remaining subjects were randomized by Interactive Voice Randomization System (IVRS). The investigator or study coordinator called the IVRS: 1) after the pre-operative inclusion/exclusion checklist confirmed eligibility and the signature page of the subject informed consent form was signed and dated, and; 2) within 14 days before the scheduled surgery date. Subjects were assigned a treatment, either study or control surgery, according to a stratified randomization schedule (by NDI level) with institution balancing. The treatment-assignment was performed using a 2:1 ratio of investigational recipients to control recipients. After assigning treatment, the investigator was not blinded to the treatment. Subjects remained masked to the treatment group assignment until surgery had been performed to minimize the potential for disproportionate drop-outs in the control group. Because masking after surgery was not guaranteed (i.e. the subject would know based on post-operative requirements or X-ray images), the sponsor did not conceal assignment from the subject after surgery. The applicant is not aware of any randomized patient who was unblinded to their treatment. Patients were evaluated preoperatively, prior to discharge, and then at 6 weeks, 3 months, 6 months, 12 months, 18 months and 24 months and annually thereafter. The recommended postoperative care was according to the individual investigator's discretion and consisted of a physician-managed individual post-operative rehabilitation program which may have included the optional use of a cervical collar. Subjects were advised according to the individual physician's discretion to increase daily activity (sitting, standing and walking), shower only in absence of wound drainage, and drive after collar removal. The study excluded subjects with a current history of heavy smoking defined as more than one pack of cigarettes per day. Subjects were requested to discontinue the use of NSAIDs from one week prior to surgery until 3 months following surgery in both treatment groups. Control group subjects were permitted to use bone growth stimulators. All adverse events (device-related or not) were monitored over the course of the study and radiographic assessments were done by an independent core laboratory. Overall success was determined by data collected during the initial 24 months of follow-up. All adverse events were independently adjudicated (for seriousness and relationship to the device) by a Clinical Events Committee (CEC) comprised of three clinicians (2 neurosurgeons and 1 orthopedic surgeon) without any relationship to the study or study investigators. A Data Monitoring Committee (DMC) whose membership included a biostatistician, a bioengineer, and the same three clinicians involved in the CEC reviewed interim data during the enrollment phase. LDR Spine -Mobi-C® P110002 Page 14 of 76 {14} The study was designed using Frequentist statistical methods as a non-inferiority trial with a margin (delta) of 10%. A closed testing procedure was used to allow for superiority to be tested in the event that non-inferiority was established for the primary effectiveness endpoint. The protocol specified a sample size of 148 Mobi-C® subjects and 74 control subjects per group based on a projected 75% success rate for control subjects and 80% success rate for Mobi-C® subjects, and 80% power for a one-sided 0.05 significance level. With the addition of the anticipated 10% loss-to-follow up, the total planned randomized sample size was 164 Mobi-C® subjects and 81 ACDF control subjects. The study allowed for 1 nonrandomized training case per site, and resulted in 15 nonrandomized Mobi-C® subjects in the one level study arm. ## 1. Clinical Inclusion and Exclusion Criteria Enrollment in the one level Mobi-C® study arm was limited to patients who met the following inclusion criteria. 1. Age 18-69 years. 2. Diagnosis of radiculopathy or myeloradiculopathy of the cervical spine, with pain, paresthesias or paralysis in a specific nerve root distribution C3 through C7, including at least one of the following: - Neck and/or arm pain (at least 30 mm on the 100 mm visual analogue scale [VAS] scale). - Decreased muscle strength of at least one level on the clinical evaluation 0 to 5 scale. - Abnormal sensation including hyperesthesia or hypoesthesia; and/or - Abnormal reflexes. 3. Symptomatic at one level from C3 to C7. 4. Radiographically determined pathology at the level to be treated correlating to primary symptoms including at least one of the following: - Decreased disc height on radiography, computed tomography (CT), or magnetic resonance imaging (MRI) in comparison to a normal adjacent disc. - Degenerative spondylosis on CT or MRI. - Disc herniation on CT or MRI. 5. NDI Score of ≥ 15/50 or ≥ 30%. 6. Unresponsive to non-operative, conservative treatment (rest, heat, electrotherapy, physical therapy, chiropractic care and/or analgesics) for: - Approximately six weeks from radiculopathy or myeloradiculopathy symptom onset; or - Have the presence of progressive symptoms or signs of nerve root/spinal cord compression despite continued non-operative conservative treatment. 7. Appropriate for treatment using an anterior surgical approach, including having no prior surgery at the operative level and no prior cervical fusion procedure at any level. 8. Reported to be medically cleared for surgery. 9. Reported to be physically and mentally able and willing to comply with the Protocol, including the ability to read and complete required forms and willing and able to adhere to the scheduled follow-up visits and requirements of the Protocol. 10. Written informed consent provided by subject or subject’s legally authorized representative. LDR Spine – Mobi-C® P110002 Page 15 of 76 {15} 11. Willingness to discontinue all use of non-steroidal anti-inflammatory drugs (NSAIDs) from one week before surgery until 3 months after surgery. Patients were not permitted to enroll in the Mobi-C® study if they met any of the following exclusion criteria. 1. Reported to have an active systemic infection or infection at the operative site. 2. Reported to have a history of or anticipated treatment for active systemic infection, including HIV or Hepatitis C. 3. More than one immobile vertebral level between C1 to C7 from any cause including but not limited to congenital abnormalities and osteoarthritic “spontaneous” fusions. 4. Previous trauma to the C3 to C7 levels resulting in significant bony or disco-ligamentous cervical spine injury. 5. Reported to have had any prior spine surgery at the operative level. 6. Reported to have had a prior cervical fusion procedure at any level. 7. Axial neck pain in the absence of other symptoms of radiculopathy or myeloradiculopathy justifying the need for surgical intervention. 8. Disc height less than 3 mm as measured from the center of the disc in a neutral position and disc height less than 20% of the anterior-posterior width of the inferior vertebral body. 9. Radiographic confirmation of severe facet joint disease or degeneration. 10. Reported to have an increased risk of osteoporosis/osteopenia. This was defined as a T-score less than (worse than) -1.5 on a previous or required Hologic Sahara or dual energy X-ray absorptiometry (DEXA) scan. All subjects that met one or more of the following were to undergo a Hologic Sahara or DEXA scan as part of the study enrollment procedures: - Females 50 years and older; - Females who were post-menopausal or post-hysterectomy with oophorectomy; - Subjects taking bisphosphonate medication for the treatment of osteoporosis; and/or - Subjects with history of chronic use of high dose steroids. High dose steroid use is defined as part of Exclusion Criterion #22. All females less than 50 years of age, and all males, who had not had a Hologic Sahara or DEXA scan within six months of surgery, were screened for osteoporosis using the Simple Calculated Osteoporosis Risk Estimation (SCORE) questionnaire. Subjects whose screening suggests increased risk (SCORE greater than 6) were to undergo a Hologic Sahara or DEXA scan as part of the study enrollment procedures. 11. Reported to have Paget’s disease, osteomalacia or any other metabolic bone disease other than osteoporosis, which is addressed above. 12. Reported active malignancy that included a history of any invasive malignancy (except non-melanoma skin cancer), unless the subject had been treated with curative intent and there had been no clinical signs or symptoms of the malignancy for at least five years. 13. Symptomatic DDD or significant cervical spondylosis at more than two levels. 14. Spondylolysis. 15. Marked cervical instability on resting lateral or flexion-extension radiographs demonstrated by: - Translation ≥ 3.5 mm, and/or - Greater than 11° angular difference to that of either adjacent level. 16. Known allergy to cobalt, chromium, molybdenum or polyethylene. LDR Spine – Mobi-C® P110002 Page 16 of 76 {16} 17. Segmental angulation of greater than 11° at treatment or adjacent levels. 18. Reported pregnancy or nursing at time of enrollment, or with plans to become pregnant within the next three years. 19. Reported to have rheumatoid arthritis, lupus, or other autoimmune disease that affect the musculoskeletal system. 20. Congenital bony and/or spinal cord abnormalities that affect spinal stability. 21. Reported to have diseases or conditions that would preclude accurate clinical evaluation (e.g. neuromuscular disorders). 22. Reported concomitant conditions requiring daily, high-dose oral and/or inhaled steroids. High dose steroid use is defined as: - Daily, chronic use of oral steroids of 5 mg/day or greater. - Daily, chronic use of inhaled corticosteroids (at least twice per day). - Use of short-term (less than 10 days) oral steroids at a daily dose greater than 40 mg within one month of the study procedure. 23. Reported to have current or recent history of substance abuse (alcoholism and/or narcotic addiction) requiring intervention. 24. Clinically Severe Obesity, as defined by National Institutes of Health (NIH) Clinical Guidelines Body Mass Index (BMI) > 40). 25. Reported use of any other investigational drug or medical device within the last 30 days prior to surgery. 26. Evidence of symptomatic moderate to severe facet joint degeneration or disease where the investigator felt this was a major contributor to the subject’s pain as diagnosed by injection and imaging. 27. Reported to be taking medications known to potentially interfere with bone/soft tissue healing (e.g., high-dose oral and/or inhaled steroids, immunosuppressant medication, chemotherapeutic agents). High dose steroid use is defined as part of Exclusion Criterion #22. 28. Reported to have pending personal litigation relating to spinal injury (worker’s compensation was not an exclusion). 29. Reported to have a current history of heavy smoking (more than one pack of cigarettes per day). 30. Anticipated or potential relocation greater than 50 miles that may interfere with completion of follow-up examinations. 31. Reported to have mental illness or belonged to a vulnerable population, as determined by the investigator (e.g., prisoner or developmentally disabled), that would compromise ability to provide informed consent or compliance with follow-up requirements. 32. Reported to have an uncontrolled seizure disorder. 33. Reported to have taken epidural steroids within 14 days prior to surgery. ## 2. Follow-up Schedule All patients were scheduled to return for follow-up examinations at 6 weeks (±1 week), 3 months (±30 days), 6 months (±30 days), 12 months (±30 days), 18 months (±30 days), 24 months (±30 days), and annually thereafter (±30 days). The following parameters were measured throughout the study: Table 4. Clinical Evaluation Schedule LDR Spine –Mobi-C® P110002 Page 17 of 76 {17} | Evaluation | Pre-op | Surgery/Hospital Discharge | 6 wks | 3 mo | 6 mo | 12 mo | 18 mo | 24 mo & annually | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Neck Disability Index | X | | X | X | X | X | X | X | | Neck and Arm Pain (VAS) | X | | X | X | X | X | X | X | | Health Status (SF-12) | X | | | | X | X | X | X | | Neurological Status/Gait | X | | X | X | X | X | X | X | | Dysphagia Scale (FOSS)* | | | X | X | X | X | X | X | | Adverse Events** | X | X | X | X | X | X | X | X | | Demographic/Baseline Data | X | | | | | | | | | Operative Data | | X | | | | | | | | Medication Use | X | X | X | X | X | X | X | X | | Radiographs | | | | | | | | | | Neutral (AP & Lateral ) | X | X | X | X | X | X | X | X | | Dynamic(F/E/ RSB/LSB)§ | X | | X | X | X | X | X | X | | CT and/or MRI | X | | | | | | | | | Radiographic Outcomes: | | | | | | | | | | Fusion status | X | | | | X | X | X | X | | Device condition | X | X | X | X | X | X | X | X | | Subsidence/ migration | X | X | X | X | X | X | X | X | | Range of motion | X | X | X | X | X | X | X | X | | Radiolucency | X | | | X | X | X | X | X | | Disc height | X | X | X | X | X | X | X | X | | Patient Satisfaction | | | | X | X | X | X | X | * Functional Outcome Swallowing Scale for Dysphagia (FOSS) ** Adverse events and complications were recorded at all visits (both scheduled and unscheduled) § Dynamic radiographs included flexion (F) / extension (E) bending and right side bending (RSB)/ left side bending (LSB) radiographs ## 3. Clinical Endpoints The effectiveness of the Mobi-C® was assessed using a composite definition of study success. Effectiveness was further evaluated by monitoring improvement in the Neck Disability Index (NDI), neck and arm pain based on a Visual Analog Scale (VAS), and quality of life using the short-form 12 questionnaire (SF-12) as well as patient satisfaction compared to the ACDF control group. The same criteria were used to measure success in both groups. LDR Spine -Mobi-C® P110002 Page 18 of 76 {18} The safety of the Mobi-C® Cervical Disc Prosthesis was assessed by comparison to the ACDF control group with respect to the nature and frequency of adverse events (overall and in terms of seriousness and relationship to the implant), secondary surgical procedures as well as maintenance or improvement in neurological status. In addition, several radiographic endpoints were considered in evaluating both safety and effectiveness, including range of motion, disc height, device condition, device subsidence, device migration, radiolucency, spinal fusion status, heterotopic ossification, and adjacent segment degeneration. According to the IDE protocol, an individual patient in either treatment group was considered a success if the following criteria were met at 24 months: - Improvement in NDI of at least 15/50 points in subjects with a baseline NDI score of ≥ 30/50 points, or a 50% improvement in subjects with a baseline NDI score of < 30/50 points; - No study failures due to secondary surgical interventions at the index level. - Absence of major complications defined as radiographic failure, neurological failure, or failure by adverse event as adjudicated by the CEC. A variation of the primary endpoint analysis was prospectively planned to assess subject success when major complications due to radiographic assessment were removed from the analysis. This variation was considered in order to compare the treatment groups after removing the radiographic assessments altogether. Secondary endpoints, measured in both treatment groups, included neck pain (VAS), arm pain (VAS), muscle strength, sensory deficit, significant neurological deterioration, adjacent segment degeneration, displacement or migration of the device, range of motion, radiolucency, quality of life (SF-12), Dysphagia (FOSS scale), and gait analysis (Nurick’s classification). Overall study success criteria were based on a comparison of individual patient success rates, such that the patient success rate for the Mobi-C® investigational group must be non-inferior to that of the ACDF fusion control group. Frequentist statistical methods were used to test for non-inferiority using an exact 95% one-sided confidence bound for the difference between the study and control success rates; if a 10% offset could be ruled out according to the 95% lower bound, then superiority was to be tested. A closed testing procedure was used to allow for superiority to be tested in the event that non-inferiority was established for the primary effectiveness endpoint. ## B. Accountability of PMA Cohort A total of 260 subjects completed study surgery. This included 179 subjects treated with Mobi-C® (164 randomized, 15 training) and 81 ACDF control subjects. There were an additional 11 subjects who were randomized, but withdrew prior to surgery. At the time of database lock, of the 260 subjects with surgery, complete 24 month primary endpoint data was available for 148 Mobi-C® patients (94.3%), 69 ACDF control patients (92.0%) and 15 non-randomized Mobi-C® patients (100%). At this time point, 135 Mobi-C® patients (86%), 61 ACDF control patients LDR Spine -Mobi-C® P110002 Page 19 of 76 {19} (81.3%) and 15 non-randomized Mobi-C® patients (100%) presented with complete data within the FDA Guidance Window. As the protocol specified follow-up windows were narrower than those specified in FDA guidance documents, accountability according to protocol-specified visits windows has also been provided. A summary of patient accountability data for the 12 month, 24 month, and 36 month follow-up visits is provided in Table 5, and a summary of data available at 24 months for each specific evaluation is provided in Table 6. Table 5. Patient Accountability (based on treatment assignment) | Number of Patients | 12 Months (±2 Months) | | | 24 Months (±2 Months) | | | 36 Months (±2 Months) | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Mobi-C® | ACDF | Training | Mobi-C® | ACDF | Training | Mobi-C® | ACDF | Training | | w/ Surgery | 164 | 81 | 15 | 164 | 81 | 15 | 164 | 81 | 15 | | Theoretical | 164 | 81 | 15 | 164 | 81 | 15 | 164 | 81 | 15 | | Deaths | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Failures1 | 5 | 4 | 0 | 7 | 6 | 0 | 8 | 7 | 0 | | Not yet overdue | - | - | - | - | - | - | - | - | - | | Expected2 | 159 | 77 | 15 | 157 | 75 | 15 | 156 | 74 | 15 | | Actual, efficacy3 (% Follow-up) | 147 (92.5%) | 65 (84.4%) | 15 (100.0%) | 148 (94.3%) | 69 (92.0%) | 15 (100.0%) | 128 (82.1%) | 56 (75.7%) | 15 (100.0%) | | Actual, efficacy in window4 (% Follow-up) | 137 (86.2%) | 60 (77.9%) | 15 (100.0%) | 135 (86.0%) | 61 (81.3%) | 15 (100.0%) | 116 (74.4%) | 51 (68.9%) | 14 (93.3%) | | Actual, any data5 (% Follow-up) | 148 (93.1%) | 67 (87.0%) | 15 (100.0%) | 148 (94.3%) | 69 (92.0%) | 15 (100.0%) | 136 (87.2%) | 57 (77.0%) | 15 (100.0%) | ${}^{1}$ A failure is any patient who experienced a major complication via the CEC assessment of adverse events or was a study failure due to subsequent surgical intervention. Note that this row is cumulative. Expected equals theoretical minus cumulative failures. 3 Refers to any patient having a value for the composite endpoint, i.e., for patient success, if all composite endpoint measures were collected and successes for that particular timepoint, or for patient failure, at least one composite endpoint measure was a failure for that particular timepoint. 4Refers to defined follow-up windows from the FDA Guidance Document entitled "Clinical Data Presentations for Orthopedic Device Applications" (2004): 6 wks: $28 \leq \text{day} \leq 56$ , 3 mo: $77.25 \leq \text{day} \leq 105.25$ , 6 mo: $152.5 \leq \text{day} \leq 212.5$ , 12 mo: $305 \leq \text{day} \leq 425$ , 18 mo: $487.5 \leq \text{day} \leq 607.5$ , 24 mo: $670 \leq \text{day} \leq 790$ 5Any data refers to patients with any evaluation data available for that visit. That is, the patient appears at the visit. LDR Spine -Mobi-C® P110002 {20} Table 6. Patient Data Accounting at Month 24 | Parameter | Mobi-C® | ACDF | Training | | --- | --- | --- | --- | | Total Randomized | 169 | 87 | 15 | | Total Treated1 | 164 | 81 | N/A | | Safety Population2 | 164 | 81 | 15 | | As-treated3 | 152 | 72 | N/A | | Composite Effectiveness Endpoint4 | 156 (95.1 %) | 75 (92.6%) | 15 (100.0%) | | NDI† | 155 (94.5 %) | 70 (86.4%) | 15 (100.0%) | | VAS Neck and Arm Pain† | 155 (94.5 %) | 70 (86.4%) | 15 (100.0%) | | SF-12† | 153 (93.3%) | 70 (86.4%) | 15 (100.0%) | | Patient Satisfaction† | 155 (94.5 %) | 70 (86.4%) | 15 (100.0%) | | Dysphagia Scale (FOSS) † | 155 (94.5 %) | 70 (86.4%) | 15 (100.0%) | | Neurological Exam† | 155 (94.5 %) | 70 (86.4%) | 15 (100.0%) | | Radiologic Assessments† | | | | | Radiographic major complication | 156 (95.1 %) | 75 (92.6%) | 15 (100.0%) | | ROM | 155 (94.5%) | 69 (85.2%) | 15 (100.0%) | | Adjacent segment degeneration | 153 (93.3%) | 68 (84.0%) | 15 (100.0%) | | Migration / Subsidence | 155 (94.5%) | 69 (85.2%) | 15 (100.0%) | | Radiolucency | 155 (94.5%) | 69 (85.2%) | 15 (100.0%) | | Change in FSU Height | 154 (93.9%) | 69 (85.2%) | 15 (100.0%) | 1 Refers to all subjects who were randomized and received surgery. 2 Refers to all treated subjects, randomized and training. 3 Refers to all subjects who were randomized, received surgery as specified in the protocol, and met all eligibility criteria 4 All treated subjects for which a composite effectiveness endpoint value (success or failure) was known. † Accounting is affected by subjects lost to follow up and/or missing data. Throughout this summary, the population of all subjects treated with surgery, including randomized Mobi-C® subjects (N=164), randomized ACDF control subjects (N=81), and Mobi-C® non-randomized training subjects (N=15) will be used for safety analyses and will be termed as the "Safety Population." The as treated population (also termed "Primary Analysis Population") is used for effectiveness analyses (164 randomized Mobi-C® subjects, 81 randomized ACDF control subjects). # C. Study Population Demographics and Baseline Parameters The demographics of the study population are consistent with demographics reported for prior cervical artificial disc studies conducted in the US. Demographic data showed that the treatment groups were well-balanced and no statistically significant differences were noted in the demographic characteristics, as shown below (Table 7). LDR Spine -Mobi-C® P110002 {21} Table 7. Patient Demographics and Baseline Characteristics – Primary Analysis Population | Demographic Measure | Randomized Mobi-C® (N=164) | Non-Randomized Mobi-C® (N=15) | Randomized ACDF (N=81) | P-Value (Randomized Groups) | | --- | --- | --- | --- | --- | | Gender | | | | | | Male | 78 (47.6%) | 6 (40.0%) | 36 (44.4%) | 0.6843** | | Female | 86 (52.4%) | 9 (60.0%) | 45 (55.6%) | | | Age (years) | 43.3 ±9.23 Range: 21 - 67 | 43.0±8.10 Range: 22 - 54 | 44.0 ±8.21 Range: 27-65 | 0.5657*** | | Ethnicity | | | | | | Hispanic or Latino | 3 (1.8%) | 1 (6.7%) | 2 (2.5%) | 0.6667** | | Not Hispanic or Latino | 161 (98.2%) | 14 (93.3%) | 79 (97.5%) | | | Race | | | | | | American Indian Alaska Native | 2 (1.2%) | 1 (6.7%) | 1 (1.2%) | | | Caucasian | 152 (92.7%) | 14 (93.3%) | 69 (85.2%) | | | Asian | 3 (1.8%) | 0 | 1 (1.2%) | 0.0710** | | Black or African American | 4 (2.4%) | 0 | 10 (12.3%) | | | Native Hawaiian/other Pacific Islander | 1 (0.6%) | 0 | 0 | | | Other | 2 (1.2%) | 0 | 0 | | | Height (in) | 67.90 ±3.960 Range: 58.0-82.0 | 67.65±2.878 Range: 64.0 - 74.0 | 67.02 ±3.714 Range: 60.0-77.0 | 0.0952*** | | Weight (lbs) | 180.06 ±38.510 Range: 107.0 -289.4 | 177.89±38.808 Range: 131.0 - 247.0 | 176.16 ±36.598 Range: 106.0 - 270.0 | 0.4494*** | | BMI (kg/m²) | 27.28 ±4.42 Range: 17.91 - 37.88 | 27.14±4.67 Range: 20.46 - 38.73 | 27.39 ±4.18 Range: 17.23 - 39.15 | 0.8460*** | | Smoke more than one pack per day (yes)* | 0 | 0 | 0 | >0.9999** | | History non-op care (yes): | | | | | | Pain Medication¹ | 152 (92.7%) | 13 (86.7%) | 79 (91.4%) | 0.0099** | | Opioid Use² | - | - | - | - | | Opium Alkaloid | 23 (14.0%) | 3 (20.0%) | 5 (6.2%) | 0.0875** | | Semi-Synthetic Opioid Derivative | 87 (53.0%) | 6 (40.0%) | 44 (54.3%) | 0.8922** | | Synthetic Opioid | 20 (12.2%) | 3 (20.0%) | 7 (8.6%) | 0.5170** | | Physical therapy | 63 (38.4%) | 7 (46.7%) | 34 (42.0%) | 0.7356** | | Collar | 19 (11.6%) | 0 | 11 (13.6%) | 0.3905** | | Chiropractic | 43 (26.2%) | 3 (20.0%) | 16 (19.8%) | 0.5029** | | Cervical Traction | 37 (22.6%) | 5 (33.3%) | 17 (21.0%) | 0.5596** | | Bedrest / Immobilization | 87 (53.0%) | 9 (60.0%) | 38 (46.9%) | 0.5542** | | Acupuncture | 9 (5.5%) | 1 (6.7%) | 5 (6.2%) | 0.8255** | | Work Status (Being able to Work) | 108 (65.9%) | 13 (86.7%) | 46 (56.8%) | 0.3264** | | Driving Status (Being able to drive) | 155 (94.5%) | 14 (93.3%) | 79 (97.5%) | 0.5035** | *Data on amount and length of tobacco use was not captured. **Using Fisher Exact test to compare frequencies between the treatments. ***Using unpaired t test to compare across treatment group. ¹Aggregate usage of medications determined to be Pain Medication presented for baseline comparison. ²Opioid usage (aggregate) with specific categories is presented separately as a subset of Pain Medication. Note – ‘Injections’ were not categorically defined in the Study Protocol, and as such are not presented here. LDR Spine –Mobi-C® P110002 Page 22 of 76 {22} The mean baseline pre-operative assessments for NDI, VAS neck pain, VAS arm pain, and both component scales of SF-12 were also similar between treatment groups. There were no statistical differences between pre-operative neurological status or range of motion between the groups, as shown in Table 8. Table 8. Preoperative Evaluation of Endpoints | Variable | Randomized Mobi-C® (N=164) | Non-Randomized Mobi-C® (N=15) | Randomized ACDF (N=81) | P-Value (Randomized Groups) | | --- | --- | --- | --- | --- | | NDI | 53.98±14.038 | 46.8±15.38 | 54.15±14.642 | 0.9290** | | VAS Neck Pain | 70.76 ±22.392 | 65.67±24.189 | 70.14±21.478 | 0.8354** | | VAS Left Arm Pain | 46.66 ±36.499 | 38.83±37.374 | 55.33±37.326 | 0.0839** | | VAS Right Arm Pain | 40.98 ±36.198 | 26.63±28.812 | 34.83±35.635 | 0.2104** | | SF-12 PCS | 32.451 ±5.9075 | 34.948±5.6139 | 33.821±6.3590 | 0.1055** | | SF-12 MCS | 42.107 ±13.1166 | 42.895±13.3983 | 42.151±10.4407 | 0.9792** | | Neurological Status (normal†) | | | | | | Motor | 72 (43.9%) | 8 (53.3%) | 31 (38.3%) | 0.4131* | | Sensory | | | | | | Light Touch | 79 (48.2%) | 9 (60.0%) | 41 (50.6%) | 0.7862* | | Pin Prick | 79 (48.2%) | 7 (46.7%) | 45 (55.6%) | 0.2816* | | Reflexes | 74 (45.1%) | 5 (33.3%) | 38 (46.9%) | 0.8916* | | Other assessments (gait‡) | 160 (97.6%) | 15 (100.0%) | 75 (94.9%)³ | 0.2796*³ | | Baseline ROM Flexion-extension (°) | 8.21±4.493 | 8.59±4.918 | 7.48±4.066 | 0.2313** | | Baseline ROM Lateral bending (mm) | 5.04±2.897 | 4.84±2.370 | 5.38±3.218 | 0.4277** | *Using Fisher Exact test to compare frequencies between the treatments **Using unpaired t-test to compare across treatment groups ¹ Normal defined as normal status for both left and right sided assessments. ² Gait was the only other neurological assessment performed, per the study protocol. ³ Two ACDF subjects did not have baseline gait data available; these values are based on 79 subjects. LDR Spine –Mobi-C® P110002 Page 23 of 76 {23} D. Safety and Effectiveness Results 1. Safety Results The analysis of safety was based on the Safety Population cohort of 260 total patients with surgery (164 randomized Mobi-C® patients, 15 non-randomized Mobi-C® patients, and 81 ACDF control patients). Adverse events that occurred in the PMA clinical study: Summary A summary of the total number of adverse events is shown in Table 9. Adverse events were classified by both the Clinical Events Committee (CEC) and the Investigator for relationship to the device and for seriousness of the event. This information is presented in Table 9. The overall adverse event rate (defined as the percentage of patients experiencing at least 1 adverse event in each category) was similar for the randomized Mobi-C® group (95.1%), non-randomized Mobi-C® training group (93.3%), and ACDF control group (92.6%). LDR Spine –Mobi-C® P110002 Page 24 of 76 {24} Table 9. Summary of Adverse Events through Month 24 – Safety Population | | Mobi-C® Non-Randomized (N=15) | | | Mobi-C® Randomized (N=164) | | | ACDF with Anterior Cervical Plate (N=81) | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Events N | Subjects N (%) | Subject-Level CI* | Events N | Subjects N (%) | Subject-Level CI*** | Events N | Subjects N (%) | Subject-Level CI*** | Event Level P-value* | Subject Level P-value** | | All Adverse Events | 89 | 14 (93.3%) | (0.681, 0.998) | 1140 | 156 (95.1%) | (0.906, 0.979) | 688 | 75 (92.6%) | (0.846, 0.972) | 0.2081 | 0.5591 | | Treatment-Emergent Adverse Events | 89 | 14 (93.3%) | (0.681, 0.998) | 1140 | 156 (95.1%) | (0.906, 0.979) | 685 | 75 (92.6%) | (0.846, 0.972) | 0.2173 | 0.5591 | | Related Adverse Events (a) | 9 | 3 (20.0%) | (0.043, 0.481) | 70 | 31 (18.9%) | (0.132, 0.257) | 63 | 20 (24.7%) | (0.158, 0.355) | 0.1706 | 0.3178 | | Definitely Related | 0 | 0 | | 8 | 7 (4.3%) | (0.017, 0.086) | 7 | 6 (7.4%) | (0.028, 0.154) | 0.3566 | 0.3656 | | Possibly Related | 9 | 3 (20.0%) | (0.043, 0.481) | 62 | 27 (16.5%) | (0.111, 0.230) | 56 | 19 (23.5%) | (0.148, 0.342) | 0.1941 | 0.2237 | | Related Adverse Events (b) | 6 | 4 (26.7%) | (0.078, 0.551) | 66 | 39 (23.8%) | (0.175, 0.310) | 58 | 23 (28.4%) | (0.189, 0.395) | 0.1224 | 0.4391 | | Definitely Related | 0 | 0 | | 1 | 1 (0.6%) | (0.000, 0.034) | 2 | 2 (2.5%) | (0.003, 0.086) | 0.3144 | 0.2547 | | Possibly Related | 6 | 4 (26.7%) | (0.078, 0.551) | 65 | 38 (23.2%) | (0.169, 0.304) | 56 | 23 (28.4%) | (0.189, 0.395) | 0.1326 | 0.4327 | | Serious Adverse Events | 5 | 2 (13.3%) | (0.017, 0.405) | 60 | 30 (18.3%) | (0.127, 0.251) | 52 | 21 (25.9%) | (0.168, 0.369) | 0.2220 | 0.1828 | | Related Serious Adverse Events (c) | 2 | 1 (6.7%) | (0.002, 0.319) | 5 | 3 (1.8%) | (0.004, 0.053) | 15 | 6 (7.4%) | (0.028, 0.154) | 0.1524 | 0.0629 | | Definitely Related | 0 | 0 | | 1 | 1 (0.6%) | (0.000, 0.034) | 5 | 5 (6.2%) | (0.020, 0.138) | 0.0468 | 0.0160 | | Possibly Related | 2 | 1 (6.7%) | (0.002, 0.319) | 4 | 3 (1.8%) | (0.004, 0.053) | 10 | 3 (3.7%) | (0.008, 0.104) | 0.2818 | 0.4001 | | Related Serious Adverse Events (d) | 1 | 1 (6.7%) | (0.002, 0.319) | 7 | 5 (3.0%) | (0.010, 0.070) | 13 | 6 (7.4%) | (0.028, 0.154) | 0.1723 | 0.1860 | | Definitely Related | 0 | 0 | - | 0 | 0 | - | 2 | 2 (2.5%) | (0.003, 0.086) | 0.1586 | 0.1084 | | Possibly Related | 1 | 1 (6.7%) | (0.002, 0.319) | 7 | 5 (3.0%) | (0.010, 0.070) | 11 | 4 (4.9%) | (0.014, 0.122) | 0.2725 | 0.4832 | | Unanticipated Adverse Device Effects | 0 | 0 | - | 0 | 0 | - | 0 | 0 | - | | >0.9999 | * The event-level incidences between Mobi-C® Randomized and ACDF treatment groups will be analyzed using an unpaired t-test. ** The subject-level p-value between Mobi-C® Randomized and ACDF treatment groups will be calculated using Fisher Exact test. *** The subject-level incidences of these outcomes will be analyzed using a 95% two-sided Binomial exact confidence interval. (a) Adverse events classified by the investigator as possibly or definitely related to study device. (b) Adverse events classified by CEC members as possibly or definitely related to study device. (c) Serious adverse events classified by the investigator as possibly or definitely related to study device. (d) Serious adverse events classified by CEC members as possibly or definitely related to study device. LDR Spine -Mobi-C® P110002 Page 25 of 76 {25} # Adverse Events by Level of Treatment Table 10a provides summary data on the number of adverse events in each treatment group, including statistical analysis and comparison between the randomized and non-randomized Mobi-C® subjects. Table 10b provides data on the number of adverse events in each treatment group stratified by level of treatment. There was a trend across levels toward fewer device-related AEs, serious AEs, and device-related serious AEs for the Mobi-C® group. Across treatment groups, relatively fewer subjects were treated at the C3-4 (N=5) and C4-5(N=13) compared with treatment at the C5-6 (N=146) and C6-7 (N=96) levels. Table 10a. Summary of Adverse Events through Month 24 – Safety Population | | Mobi-C® Non-Randomized (N=15) | | | Mobi-C® Randomized (N=164) | | | ACDF with Anterior Cervical Plate (N=81) | | | P-values | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Events N | Subjects N (%) | Subject-Level CI* | Events N | Subjects N (%) | Subject-Level CI*** | Events N | Subjects N (%) | Subject-Level CI*** | Event Level P-value* | Subject Level P-value** | | All Adverse Events | 89 | 14 (93.3%) | (0.681, 0.998) | 1140 | 156 (95.1%) | (0.906, 0.979) | 688 | 75 (92.6%) | (0.846, 0.972) | 0.2081 | 0.5591 | | Treatment-Emergent Adverse Events | 89 | 14 (93.3%) | (0.681, 0.998) | 1140 | 156 (95.1%) | (0.906, 0.979) | 685 | 75 (92.6%) | (0.846, 0.972) | 0.2173 | 0.5591 | CI = confidence interval * The event-level incidences between Mobi-C® Randomized and ACDF groups are presented using an unpaired t-test. ** The subject-level p-values between Mobi-C® Randomized and ACDF groups are calculated using Fisher Exact test. *** The subject-level incidences of these outcomes are analyzed using a 95% two-sided Binomial exact confidence interval. Table 10b. Total Adverse Events by Level Treated – Safety Population | | Mobi-C® (N=179)* | | | ACDF (N=81) | | | | --- | --- | --- | --- | --- | --- | --- | | | Events N | Subjects N (%) | Subject-Level CI** | Events N | Subjects N (%) | Subject-Level CI** | | Treated Segment: C3-C4 | (N=1) | | | (N=4) | | | | TEAEs | 5 | 1 (100%) | | 24 | 3 (75.0%) | (0.194, 0.994) | | Treated Segment: C4-C5 | (N=11) | | | (N=2) | | | | TEAEs | 97 | 11 (100%) | | 18 | 1 (50.0%) | (0.013, 0.987) | | Treated Segment: C5-C6 | (N=100) | | | (N=46) | | | | TEAEs | 705 | 95 (95.0%) | (0.887, 0.984) | 478 | 44 (95.7%) | (0.852, 0.995) | | Treated Segment: C6-C7 | (N=67) | | | (N=29) | | | | TEAEs | 422 | 63 (94.0%) | (0.854, 0.983) | 165 | 27 (93.1%) | (0.772, 0.992) | TEAE = treatment emergent adverse event * Includes all Mobi-C® study subjects. **The subject-level incidences of these outcomes are analyzed using a 95% two-sided Binomial exact confidence interval. ## All Adverse Events The adverse events reported in the PMA from all 260 total patients (164 randomized Mobi-C® patients, 81 ACDF control patients, 15 non-randomized Mobi-C® patients) are shown in Table 11. This table includes adverse events from all patients, randomized and non-randomized, to establish the safety profile of the device for the primary study endpoint (24 months). Adverse events are listed in alphabetical order according to adverse event categories. Definitions of the adverse event categories are provided in Table 12. Table 13 is presented in a similar fashion as LDR Spine –Mobi-C® P110002 Page 26 of 76 {26} Table 11 (using the categories as defined in Table 12), and includes all known adverse event data at the time of PMA submission, including all available subject AE data through 60 months of follow up. 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. Events per patient are based on the number of adverse events, divided by the number of patients. The most commonly reported categories of adverse events were Neck Pain (in 41.3% of randomized and non-randomized Mobi-C® subjects and 45.7% of ACDF subjects), Arm Pain (in 25.7% of all Mobi-C® subjects and 24.7% of ACDF subjects), Headache (in 25.1% of all Mobi-C® subjects and 32.1% of ACDF subjects), Trauma (in 26.3% of all Mobi-C® subjects and 24.7% of ACDF subjects), Back Pain (in 24.6% of all Mobi-C® subjects and 22.2% of ACDF subjects), Neurological – Neck (in 22.9% of all Mobi-C® subjects and 25.9% of ACDF subjects), Neurological – Upper Extremity-Sensory (in 37.4% of all Mobi-C® subjects and 39.5% of ACDF subjects), Shoulder Pain (in 21.8% of all Mobi-C® subjects and 25.9% of ACDF subjects), and Other Pain (in 57.0% of all Mobi-C® subjects and 58.0% of ACDF subjects). Notably, the ACDF subjects reported higher rates for dysphagia and dysphonia (21%) compared to Mobi-C® subjects (11.2%). Higher rates of local wound events were noted in ACDF subjects (22.2%) compared to Mobi-C® subjects (11.2%). The nonunion rate in ACDF subjects was 4.9%. The investigator reported heterotopic ossification rate at the level of surgery was 2.8% in Mobi-C® subjects. No deaths or unanticipated adverse device effects were reported during the study. LDR Spine -Mobi-C® P110002 Page 27 of 76 {27} Table 11. All Treatment Emergent Adverse Events through 24 Months in US IDE Study – All Study Subjects | | Surgery to Discharge | | Discharge to Week 6 | | Week 6 to Month 3 | | Months 3 to 6 | | Months 6 to 12 | | Months 12 to 18 | | Months 18 to 24 | | Mobi-C® | | ACDF | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Complication | M | F | M | F | M | F | M | F | M | F | M | F | M | F | #Patients (% of 179) | Total Events | #Patients (% of 81) | Total Events | | All Adverse Events1 | 148 | 53 | 149 | 76 | 137 | 134 | 156 | 96 | 288 | 166 | 232 | 102 | 140 | 84 | 170 (95.0%) | 1229 | 75 (92.6%) | 688 | | Anatomy/Technical Difficulty | 2 | 0 | 0 | 1 | 2 | 2 | 1 | 0 | 1 | 1 | 5 | 0 | 1 | 0 | 11 (6.1%) | 12 | 2 (2.5%) | 4 | | Cervical – Study Surgery | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 4 (2.2%) | 4 | 2 (2.5%) | 3 | | Cervical – Non Study Surgery | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 5 (2.8%) | 6 | 1 (1.2%) | 1 | | Non-Cervical | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 (1.1%) | 2 | 0 (0.0%) | 0 | | Cancer | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 3 | 0 | 4 (2.2%) | 5 | 1 (1.2%) | 2 | | Cardiovascular | 6 | 1 | 2 | 2 | 0 | 0 | 4 | 2 | 6 | 2 | 4 | 3 | 4 | 0 | 20 (11.2%) | 26 | 10 (12.3%) | 10 | | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Dysphagia/Dysphonia | 9 | 5 | 7 | 5 | 4 | 2 | 0 | 1 | 2 | 3 | 1 | 4 | 3 | 0 | 20 (11.2%) | 26 | 17 (21.0%) | 20 | | Dysphagia | 8 | 2 | 6 | 5 | 4 | 2 | 0 | 1 | 1 | 3 | 1 | 4 | 2 | 0 | 19 (10.6%) | 22 | 15 (18.5%) | 17 | | Dysphonia | 1 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 3 (1.7%) | 4 | 3 (3.7%) | 3 | | Gastrointestinal | 28 | 9 | 2 | 3 | 2 | 2 | 2 | 1 | 16 | 11 | 9 | 6 | 1 | 5 | 39 (21.8%) | 60 | 15 (18.5%) | 37 | | Heterotopic Ossification | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 5 | 2 | 2 | 1 | 2 | 1 | 9 (5.0%) | 10 | 4 (4.9%) | 4 | | Cervical - Index Level | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 0 | 1 | 0 | 5 (2.8%) | 5 | 0 (0.0%) | 0 | | Cervical - Adjacent Level | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 (0.6%) | 1 | 1 (1.2%) | 1 | | Non-Cervical | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 1 | 1 | 1 | 4 (2.2%) | 4 | 3 (3.7%) | 3 | | Infection | 3 | 1 | 14 | 4 | 5 | 8 | 7 | 0 | 9 | 8 | 8 | 5 | 5 | 2 | 33 (18.4%) | 51 | 20 (24.7%) | 28 | | Superficial Wound – Cervical | 2 | 0 | 5 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 (3.4%) | 7 | 1 (1.2%) | 1 | | Deep Wound – Cervical | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Other Wound - Non Study Surgery | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 1 (0.6%) | 1 | 3 (3.7%) | 3 | | Systemic | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 3 | 3 | 2 | 0 | 1 | 0 | 8 (4.5%) | 9 | 2 (2.5%) | 3 | | Local | 1 | 0 | 7 | 4 | 5 | 7 | 6 | 0 | 5 | 4 | 6 | 5 | 4 | 1 | 20 (11.2%) | 34 | 18 (22.2%) | 21 | | Malpositioned Implant | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 (1.1%) | 2 | 1 (1.2%) | 1 | | Neck and/or Arm Pain | 30 | 8 | 28 | 9 | 26 | 23 | 25 | 17 | 41 | 20 | 41 | 13 | 21 | 8 | 102 (57.0%) | 212 | 47 (58.0%) | 98 | | Neck Pain | 25 | 8 | 17 | 7 | 11 | 7 | 11 | 10 | 26 | 12 | 23 | 6 | 10 | 6 | 74 (41.3%) | 123 | 37 (45.7%) | 56 | | Arm Pain | 3 | 0 | 11 | 1 | 12 | 10 | 10 | 3 | 13 | 4 | 16 | 5 | 11 | 2 | 46 (25.7%) | 76 | 20 (24.7%) | 25 | | Neck And Arm Pain | 2 | 0 | 0 | 1 | 3 | 6 | 4 | 4 | 2 | 4 | 2 | 2 | 0 | 0 | 9 (5.0%) | 13 | 7 (8.6%) | 17 | | Neurological | 33 | 11 | 47 | 25 | 48 | 54 | 65 | 36 | 91 | 43 | 70 | 17 | 47 | 29 | 121 | 401 | 52 (64.2%) | 215 | LDR Spine -Mobi-C® P110002 Page 28 of 76 {28} | | Surgery to Discharge | | Discharge to Week 6 | | Week 6 to Month 3 | | Months 3 to 6 | | Months 6 to 12 | | Months 12 to 18 | | Months 18 to 24 | | Mobi-C® | | ACDF | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Complication | M | F | M | F | M | F | M | F | M | F | M | F | M | F | #Patients (% of 179) | Total Events | #Patients (% of 81) | Total Events | | | | | | | | | | | | | | | | | (67.6%) | | | | | Upper Extremity – Sensory | 4 | 2 | 17 | 11 | 25 | 45 | 31 | 24 | 43 | 20 | 36 | 9 | 19 | 15 | 67 (37.4%) | 175 | 32 (39.5%) | 126 | | Upper Extremity – Motor | 7 | 3 | 5 | 2 | 3 | 2 | 5 | 2 | 10 | 5 | 5 | 2 | 8 | 4 | 26 (14.5%) | 43 | 15 (18.5%) | 20 | | Upper Extremity – Reflex | 0 | 0 | 5 | 10 | 12 | 4 | 11 | 5 | 6 | 1 | 4 | 0 | 6 | 0 | 18 (10.1%) | 44 | 7 (8.6%) | 20 | | Lower Extremity – Sensory | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 9 | 0 | 6 | 2 | 4 | 1 | 11 (6.1%) | 22 | 2 (2.5%) | 3 | | Lower Extremity – Motor | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 4 | 1 | 1 | 0 | 2 | 1 | 6 (3.4%) | 9 | 4 (4.9%) | 4 | | Lower Extremity – Reflex | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 (0.0%) | 0 | 1 (1.2%) | 1 | | Upper & Lower Extremity - Sensory | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 (0.6%) | 1 | 1 (1.2%) | 1 | | Upper & Lower Extremity – Motor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Upper & Lower Extremity - Reflex | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Neck | 10 | 5 | 10 | 1 | 4 | 0 | 9 | 3 | 10 | 7 | 6 | 0 | 2 | 5 | 41 (22.9%) | 51 | 21 (25.9%) | 21 | | Back | 1 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 1 | 1 | 1 | 1 | 2 | 0 | 7 (3.9%) | 8 | 2 (2.5%) | 2 | | Spinal Cord Disturbance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Gait Disturbance | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.6%) | 1 | 1 (1.2%) | 1 | | Non Specific | 5 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 6 (3.4%) | 6 | 1 (1.2%) | 1 | | Other* | 3 | 0 | 7 | 1 | 3 | 2 | 6 | 0 | 7 | 7 | 11 | 3 | 4 | 2 | 35 (19.6%) | 41 | 8 (9.9%) | 15 | | Non-Union | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 (0.0%) | 0 | 4 (4.9%) | 4 | | Other** | 17 | 8 | 14 | 10 | 7 | 3 | 12 | 9 | 25 | 19 | 25 | 9 | 14 | 8 | 77 (43.0%) | 114 | 33 (40.7%) | 66 | | Other Pain | 12 | 3 | 18 | 7 | 33 | 27 | 29 | 18 | 60 | 29 | 48 | 35 | 26 | 25 | 102 (57.0%) | 226 | 47 (58.0%) | 144 | | Shoulder | 4 | 1 | 6 | 2 | 6 | 7 | 8 | 2 | 12 | 5 | 12 | 8 | 7 | 6 | 39 (21.8%) | 55 | 21 (25.9%) | 31 | | Back | 2 | 0 | 2 | 2 | 6 | 8 | 5 | 3 | 15 | 7 | 13 | 4 | 7 | 6 | 44 (24.6%) | 50 | 18 (22.2%) | 30 | | Torso | 0 | 0 | 2 | 0 | 0 | 1 | 1 | 0 | 4 | 2 | 0 | 1 | 0 | 0 | 5 (2.8%) | 7 | 3 (3.7%) | 4 | | Lower Extremity | 1 | 0 | 3 | 0 | 4 | 0 | 3 | 5 | 12 | 3 | 13 | 15 | 4 | 6 | 26 (14.5%) | 40 | 12 (14.8%) | 29 | | Headache | 5 | 1 | 3 | 3 | 15 | 10 | 9 | 7 | 14 | 11 | 7 | 4 | 5 | 5 | 45 (25.1%) | 58 | 26 (32.1%) | 41 | | Other*** | 0 | 1 | 2 | 0 | 2 | 1 | 3 | 1 | 3 | 1 | 3 | 3 | 3 | 2 | 15 (8.4%) | 16 | 8 (9.9%) | 9 | | Respiratory | 3 | 2 | 1 | 1 | 1 | 3 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 6 (3.4%) | 6 | 6 (7.4%) | 8 | | Spinal Disorder | 2 | 0 | 0 | 2 | 0 | 0 | 2 | 0 | 1 | 7 | 2 | 1 | 0 | 2 | 6 (3.4%) | 7 | 10 (12.3%) | 12 | | Cervical - Study Surgery | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 (0.6%) | 1 | 2 (2.5%) | 2 | | Cervical - Non Study Surgery | 2 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 1 | 2 | 0 | 0 | 1 | 5 (2.8%) | 6 | 3 (3.7%) | 3 | | Non-Cervical | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 1 | 0 | 1 | 0 (0.0%) | 0 | 5 (6.2%) | 7 | LDR Spine -Mobi-C® P110002 Page 29 of 76 {29} | | Surgery to Discharge | | Discharge to Week 6 | | Week 6 to Month 3 | | Months 3 to 6 | | Months 6 to 12 | | Months 12 to 18 | | Months 18 to 24 | | Mobi-C® | | ACDF | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Complication | M | F | M | F | M | F | M | F | M | F | M | F | M | F | #Patients (% of 179) | Total Events | #Patients (% of 81) | Total Events | | Trauma | 1 | 1 | 14 | 2 | 9 | 7 | 7 | 9 | 22 | 9 | 9 | 6 | 8 | 4 | 47 (26.3%) | 70 | 20 (24.7%) | 38 | | Upper Extremity Nerve Entrapment | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 1 | 4 | 0 | 3 | 1 | 2 | 0 | 8 (4.5%) | 9 | 4 (4.9%) | 5 | | Urogenital | 0 | 3 | 2 | 1 | 0 | 1 | 0 | 1 | 5 | 6 | 2 | 0 | 2 | 0 | 9 (5.0%) | 11 | 9 (11.1%) | 12 | | Vascular Intraop | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.6%) | 1 | 0 (0.0%) | 0 | | Wound Issue - Non-Infection | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 (0.6%) | 1 | 3 (3.7%) | 3 | | Hematoma | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 (0.6%) | 1 | 3 (3.7%) | 3 | | Hematoma Evacuation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | CSF Leakage | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | M= All Mobi-C® Subjects; F = All ACDF Subjects Sum of all treatment emergent adverse events experienced in the study for each treatment group. *Neurological Other includes Neurological events not appropriately defined elsewhere in the Neurological category. This includes amnesia, convulsion, facial neurologic events (dysaesthesia, hypoaesthesia), unexplained loss of consciousness, 'other' nerve compression, Parkinson's disease, and stroke. **Other includes events not appropriately defined elsewhere. This includes adverse drug reactions, allergies, anemia, anxiety, arthritis, attention deficit disorder, benign neoplasm, blood & lymphatic system disorders, complications from other medical procedures, congenital defects, dehydration, dermatitis, diabetes, dizziness, ear/eye disorders, endocrine disorders, fatigue, feeling hot, fever, gout, high/low cholesterol, immune system disorders, injury/poisoning, lupus, menopause, miscarriage, muscle atrophy, nutritional disorders, obesity, osteoarthritis, osteoporosis, other inflammation, other medical procedures, plantar fasciitis, polyps, pregnancy, psychiatric disorders, rotator cuff syndrome, skin disorders, sinus infection, social issues, sleep disorders, swelling, tendonitis, thyroid conditions, vascular disorders, and weight gain/loss. ***Other Pain Other includes events not appropriately defined elsewhere. This includes facial pain, fibromyalgia, muscle soreness, chronic pain, nerve pain and arthritis. LDR Spine -Mobi-C® P110002 Page 30 of 76 {30} Table 12. Adverse Event Categories and Subcategories | AE Category or Subcategory | Definition | | --- | --- | | Anatomy/Technical Difficulty | Includes surgical procedure related events, such as technical issues with the device or with the anatomy during surgery or post-operative. Where events are more accurately described in another category (such as ‘Malpositioned Implant’) they will be placed into the more accurate category. | | Cervical – Study Surgery | Stratified by cervical study surgery related to illustrate clinical relevance to the study. Study Surgery is intended to mean the index level, or other events directly attributed to the study surgery or device. Includes technical issues with the device or with anatomy during surgery or post-operative. | | Cervical – Non Study Surgery | Stratified by cervical non-study surgery related to illustrate clinical relevance to the study. This AE subcategory is unrelated (lacks clinical relevance) to the index level and is unrelated to study surgery. | | Non-Cervical | Non Cervical captures non-study related events, such as technical difficulty with an unrelated procedure. | | Cancer | All reported AEs of cancer (malignancy or malignant tumor/neoplasm). | | Cardiovascular | All reported AEs of the cardiovascular system. | | Death | All reports of death. | | Dysphagia/Dysphonia | | | Dysphagia | All reported AEs of Dysphagia and other terms consistent with “difficulty swallowing.” | | Dysphonia | All reported AEs of Dysphonia and other terms consistent with “voice change and/or disruption.” | | Gastrointestinal | All reported AEs of the gastrointestinal system, except those more appropriately categorized elsewhere. | | Heterotopic Ossification | | | Cervical – Index Level | All reported AEs of Heterotopic Ossification, stratified by cervical events at the index level. | | Cervical – Adjacent Level | All reported AEs of Heterotopic Ossification, stratified by cervical events at the adjacent levels. | | Non-Cervical | Events that occur outside of the cervical spine, or non-specific event reports…