prodisc C SK and prodisc C Vivo

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION | Device Generic Name: | Artificial Cervical Disc | | --- | --- | | Device Trade Name: | prodisc® C SK prodisc® C Vivo | | Device Product Code: | MJO | | Applicant's Name and Address: | Centinel Spine, LLC 900 Airport Road, Suite 3B West Chester, PA 19380 Phone: (484) 887-8810 | | Date of Panel Recommendation: | None | | Premarket Approval Application: (PMA Number) | P070001/S025 | | Date of FDA Notice of Approval: | October 10, 2025 | The original PMA (P070001) was approved on December 17, 2007, for the prodisc® C. A subsequent PMA Supplement (P070001 / S019) was approved on July 7, 2022, for the subject prodisc® C SK and prodisc® C Vivo and is indicated in skeletally mature patients for reconstruction of a single disc from C3-C7 following discectomy for intractable symptomatic cervical disc disease (SCDD). Symptomatic cervical disc disease is defined as neck or arm (radicular) pain and/or a functional/neurological deficit with at least one of the following conditions confirmed by imaging (CT, MRI, or X-rays): herniated nucleus pulposus, spondylosis (defined by the presence of osteophytes), and/or loss of disc height. The prodisc® C Total Disc Replacement is implanted via an open anterior approach. Patients receiving the prodisc® C Total Disc Replacement should have failed at least six weeks of non-operative treatment prior to implantation of the prodisc® C Total Disc Replacement. The subject PMA supplement was submitted to expand the indication for the prodisc® C SK and prodisc® C Vivo to include use of the devices at two (2) contiguous intervertebral levels in the cervical spine. ## II. INDICATIONS FOR USE The prodisc® C SK and prodisc® C Vivo are indicated for use 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 radiographic imaging (CT, MRI, X-rays): herniated nucleus pulposus, spondylosis (defined by the presence of osteophytes), and/or visible loss of disc height PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 1 of 76 {1} as compared to adjacent levels. The prodisc® C SK and prodisc® C Vivo are 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 prodisc® C SK and prodisc® C Vivo. ### III. CONTRAINDICATIONS - Fractures, infections, tumors - Spinal stenosis by hypertrophic spondylarthrosis - Cervical instability on resting (neutral) lateral or flexion-extension radiographs; translation greater than or equal to 3.5mm and/or greater than 11° of angular difference from either adjacent level - Ossification of posterior longitudinal ligament (OPLL) - Cervical anatomical deformity or malalignment (e.g., ankylosing spondylitis, scoliosis, kyphosis) at the operative or adjacent levels or anatomical compromise of the vertebral bodies or vertebral endplates at the operative levels - Osteoporosis or osteopenia defined as DEXA bone mineral density T-score less than -1.5 - Facet joint degeneration - Acute or chronic systemic, spinal, or localized infections - Allergy or sensitivity to cobalt, chromium, molybdenum, titanium or polyethylene ### IV. WARNINGS AND PRECAUTIONS - The warnings and precautions can be found in the prodisc® C SK and prodisc® C Vivo labeling. ### V. DEVICE DESCRIPTION The prodisc® C SK and prodisc® C Vivo are manufactured with chromium molybdenum alloy (Co-28Cr-6Mo (CoCrMo)) endplates (with a commercially pure titanium plasma spray coating) and an ultra-high molecular weight polyethylene (UHMWPE) inlay. The prodisc® C SK device features a midline keel oriented anterior-posterior, while the prodisc® C Vivo features six pegs oriented anterior-posterior on the lateral edges that anchor the devices to the vertebral bodies.   Figure 1: prodisc® C SK (Left), and prodisc® C Vivo (Right) Table 1 describes the available sizes and configurations of the prodisc® C SK and prodisc® C Vivo components. PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 2 of 76 {2} **Table 1: prodisc® C SK and prodisc® C Vivo Part Listing and Size Overview** | Implant Type | Catalog Number | Width (mm) | Depth (mm) | Height (mm) | | --- | --- | --- | --- | --- | | **prodisc® C SK** | | | | | | prodisc® C SK, Size M | PDCM5 | 15 | 12 | 5 | | prodisc® C SK, Size M | PDCM6 | 15 | 12 | 6 | | prodisc® C SK, Size M | PDCM7 | 15 | 12 | 7 | | prodisc® C SK, Size MD | PDCMD5 | 15 | 14 | 5 | | prodisc® C SK, Size MD | PDCMD6 | 15 | 14 | 6 | | prodisc® C SK, Size MD | PDCMD7 | 15 | 14 | 7 | | prodisc® C SK, Size L | PDCL5 | 17 | 14 | 5 | | prodisc® C SK, Size L | PDCL6 | 17 | 14 | 6 | | prodisc® C SK, Size L | PDCL7 | 17 | 14 | 7 | | prodisc® C SK, Size LD | PDCLD5 | 17 | 16 | 5 | | prodisc® C SK, Size LD | PDCLD6 | 17 | 16 | 6 | | prodisc® C SK, Size LD | PDCLD7 | 17 | 16 | 7 | | prodisc® C SK, Size XL | PDCXL5 | 19 | 16 | 5 | | prodisc® C SK, Size XL | PDCXL6 | 19 | 16 | 6 | | prodisc® C SK, Size XL | PDCXL7 | 19 | 16 | 7 | | prodisc® C SK, Size XLD | PDCXLD5 | 19 | 18 | 5 | | prodisc® C SK, Size XLD | PDCXLD6 | 19 | 18 | 6 | | prodisc® C SK, Size XLD | PDCXLD7 | 19 | 18 | 7 | | **prodisc® C Vivo** | | | | | | prodisc® C Vivo, Size M | PDVM5 | 15 | 12 | 5 | | prodisc® C Vivo, Size M | PDVM6 | 15 | 12 | 6 | | prodisc® C Vivo, Size M | PDVM7 | 15 | 12 | 7 | | prodisc® C Vivo MD | PDVMD5 | 15 | 14 | 5 | | prodisc® C Vivo MD | PDVMD6 | 15 | 14 | 6 | | prodisc® C Vivo MD | PDVMD7 | 15 | 14 | 7 | | prodisc® C Vivo L | PDVL5 | 17 | 14 | 5 | | prodisc® C Vivo L | PDVL6 | 17 | 14 | 6 | | prodisc® C Vivo L | PDVL7 | 17 | 14 | 7 | | prodisc® C Vivo LD | PDVLD5 | 17 | 16 | 5 | | prodisc® C Vivo LD | PDVLD6 | 17 | 16 | 6 | | prodisc® C Vivo LD | PDVLD7 | 17 | 16 | 7 | | prodisc® C Vivo XL | PDVXL5 | 19 | 16 | 5 | | prodisc® C Vivo XL | PDVXL6 | 19 | 16 | 6 | | prodisc® C Vivo XL | PDVXL7 | 19 | 16 | 7 | | prodisc® C Vivo XLD | PDVXLD5 | 19 | 18 | 5 | | prodisc® C Vivo XLD | PDVXLD6 | 19 | 18 | 6 | | prodisc® C Vivo XLD | PDVXLD7 | 19 | 18 | 7 | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 3 of 76 {3} ## **VI. ALTERNATIVE PRACTICES AND PROCEDURES** There are several other alternatives for the treatment of intractable radiculopathy due to a single-level or multi-level abnormality localized to the level of the disc space at one or two contiguous levels. - Nonoperative alternative treatments, which include, but are not limited to, simple neck adjustments, physical therapy, heat, traction, braces, bed rest, medications, spinal injections, or exercise programs. - Surgical alternatives, which include, but are not limited to: - Surgical decompression alone - Surgical decompression via an anterior approach with fusion using various bone grafting and anterior plating techniques - Surgical decompression with fusion using intervertebral cages, with various bone grafting techniques, with or without supplemental anterior plating - Decompression with posterior spinal systems (e.g., rods, screws, hooks, wires) - Another FDA-approved artificial cervical disc Each option has advantages and disadvantages. Patients should fully discuss the available alternatives with his or her physician to select the option that best meets their clinical condition, lifestyle, and expectations. ## **VII. MARKETING HISTORY** The original PMA (P070001) was approved on December 17, 2007, for the prodisc® C. The subject prodisc® C SK and prodisc® C Vivo devices were approved by FDA for one-level indications on July 7, 2022, under P070001/S019. Additionally, the prodisc® C Vivo has been marketed outside of the United States since 2011. The prodisc® C Vivo is currently distributed in: Argentina; Australia; Brazil; Canada; Columbia; Dubai; European Union; Hong Kong; Indonesia; Malaysia; Mexico; Qatar; Saudi Arabia; Singapore; South Africa; South Korea; Switzerland; Taiwan; Thailand; Turkey; United Kingdom; and Vietnam. The prodisc® C SK and prodisc® C Vivo have not been withdrawn from any distribution/marketing in any country for safety or effectiveness reasons. ## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH** Below is a list of the potential adverse effects (e.g., complications) identified from the prodisc® C SK and prodisc® C Vivo 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 prodisc® C SK and prodisc® C Vivo. 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. ### *Risks Associated with Any Surgical Procedure* General surgical risks include, but are not limited to: - Infection/abscess/cyst, localized or systemic - Pain at surgical site PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 4 of 76 {4} - Blood clots, including pulmonary emboli - Medication and anesthesia reactions - Phlebitis - Pneumonia - Atelectasis - Soft tissue damage - Septicemia - Hemorrhage possibly requiring a blood transfusion, with possible transfusion reaction - Myocardial infarction - Paralysis - Poor tissue healing - Cerebrovascular accident (CVA) - Death PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 5 of 76 {5} ### Anterior Cervical Surgery Risks Anterior cervical surgical risks include, but are not be limited to: - Infection/abscess/cyst, localized or systemic - Injury or damage to the trachea, esophagus, nerves or blood vessels - Dysphagia - Hoarseness - Vocal cord paralysis - Paresis - Recurrent laryngeal nerve palsy - Soft tissue damage - Spinal cord damage - Dural tear with cerebrospinal fluid leakage - Arm weakness or numbness - Bowel, bladder or sexual dysfunction - Nerve root injury - Airway obstruction - Epidural hematoma or bleeding - Epidural fibrosis - Vertebral body fracture - Dysesthesia or numbness - Paresthesia - Unresolved pain - Surgical intervention at incorrect level - Need for supplemental fixation - Spinal instability - Death ### Cervical Artificial Disc Risks Risks specific to cervical artificial discs, including the prodisc® C SK and prodisc® C Vivo, include but are not limited to: - Infection/abscess/cyst, localized or systemic - Allergic reaction to the implant materials - Implant failure - Device migration - Device subsidence - Device fatigue or fracture or breakage - Device instability - Separation of device components - Placement difficulties, device malposition - Improper device sizing - Excessive device height loss - Wear debris - Disc space collapse PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 6 of 76 {6} - Material degradation - Excessive facet loading - Kyphosis or hyper-extension - Loss of flexibility - Asymmetric range of motion (ROM) - Vertebral body fracture - Spinal cord damage, - Dural tear with cerebrospinal fluid leakage - Soft tissue damage - Epidural fibrosis - Nerve injury, paralysis or weakness that is temporary or permanent - Injury or damage to the trachea, esophagus, or blood vessels - Epidural hematoma or bleeding - Dysesthesia or numbness - Paresthesia - Failure to relieve symptoms including unresolved pain - Additional surgery due to loss of fixation, infection or injury - Spontaneous fusion due to heterotopic ossification (HO), development of bridging bone or osteophytes - Periarticular calcification and fusion - Development of spinal conditions, including but not limited to spinal stenosis, spondylolisthesis, or retrolisthesis - Removal, revision, reoperation or supplemental fixation of the disc - Osteolysis, bone loss, or bone resorption - Death For the specific adverse events that occurred in the prodisc® C SK and prodisc® C Vivo 2-Level clinical study, please see Section X. PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 7 of 76 {7} ## IX. SUMMARY OF NON-CLINICAL STUDIES A variety of testing was conducted to characterize the performance of the prodisc® C SK and prodisc® C Vivo for one-level use (and is also applicable for two-level use), including: - Static Axial Compression - Dynamic Axial Compression - Static Compression-Shear - Dynamic Compression-Shear - Subluxation - Device Expulsion - Static Inlay Expulsion - Subsidence - Mode I Wear Testing - Mode III (Third Body) Wear Testing - Mode IV (Impingement) Wear Testing - Dynamic Creep Relaxation - Cadaver Study - Explant Analyses and Evaluations - MR Compatibility - Coating Testing - Biocompatibility / Toxicity / Neurotoxicity - Device Sterilization - Shelf Life and Transit Validation Table 2: Non-Clinical Study Summary | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | **Static and Dynamic Strength** | | | | | | **Static and Fatigue under Axial Compression** | Verify static and fatigue performance under simulated physiologic conditions are sufficient to withstand in vivo compressive loads | Six (6) prodisc® C specimens were tested under static compression in 37°C deionized water at a rate of 12mm/min until failure or capacity of load cell was reached. | Must withstand the maximum compression force during maximum flexion (1164N) | Average Static compression force of 24,072N | | | | Six (6) prodisc® C specimens were tested under dynamic compression in 37°C 0.9% saline to 10,000,000 cycles, using a sinusoidal wave form at 5 Hz. | Fatigue load (10 x 10^{6} cycles runout) ≥ 150 N | Runout ≥ 1500 N | | | | Testing per ASTM F2346 | Average residual height loss after runout ≤1.5mm | All acceptance criteria were met. | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 8 of 76 {8} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | **Static and Fatigue Shear Strength** | Verify that the static and fatigue performance are sufficient to withstand anticipated in vivo shear compressive loads | Six (6) prodisc® C specimens were tested under static compression-shear at a rate of 12mm/min until failure or capacity of load cell was reached. | Must withstand the maximum compression force during maximum flexion (1164N) | Average static compression shear ultimate force of 12,945.7N | | | | Six (6) prodisc® C specimens were tested under dynamic compression-shear to 10,000,000 cycles using a sinusoidal wave form at 5 Hz. | Must withstand the maximum forces in dynamic loading (150N) | Runout at 600N in dynamic compression-shear All acceptance criteria were met. | | **Subluxation/Expulsion** | | | | | | **Subluxation** | Characterize the force needed to result in subluxation of the prodisc® C | Six (6) prodisc® C specimens were placed within the pockets of stainless steel test blocks with a preload of 100N applied along the Z-axis. The testing was performed in displacement control at a rate of 5mm/minute until the superior endplate disassociated from the inlay and complete subluxation occurred. | Subluxation force ≥ 2 N | Average subluxation force of 120.4N with 0.43mm of displacement Acceptance criteria met | | **Device Expulsion** | Characterize the prodisc® C mechanical properties via static expulsion testing on the complete implant assemblies | Nine (9) prodisc® C specimens were placed between Grade 15 polyurethane foam test blocks with an axial preload of 100N. A 4.7mm flat point load was used to push against the prodisc® C Vivo and prodisc® C SK devices, and a 5.85mm x 2.4mm flat point load was used to push against the prodisc® C Nova (out-of-scope). The static expulsion tests were performed at a rate of 6mm/minute. Additional expulsion testing conducted on 3 prodisc® C Vivo, SK and Nova (out-of-scope) M5 devices and 3 prodisc® C Vivo, SK, Nova (out-of-scope) XLD7 devices was conducted. | Must withstand the largest occurring in-vivo antero-posterior shear load of 135N | Average expulsion forces for prodisc® C Vivo: 382.4 ± 2.7N with 0.97 ± 0.27mm of displacement Average expulsion forces for prodisc® C SK: 274.8 ± 17.9N with 1.35 ± 1.36mm of displacement Additional subsidence testing demonstrated that the endplate geometry does not impact subsidence performance relative to the original prodisc® C implant. All acceptance criteria met | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 9 of 76 {9} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | **Static Inlay Expulsion Test** | Characterize the prodisc® C mechanical properties via static expulsion testing on the inlays from the mating inferior endplates | Six (6) prodisc® C specimens were placed within the pockets of the test blocks. A 5.85mm x 2.4mm flat point load was used to push against the prodisc® C Vivo, and a 4.7mm flat point load was applied against the prodisc® C Nova (out-of-scope). The testing was conducted in displacement control at a rate of 6 mm/minute. | Must withstand the largest occurring in-vivo antero-posterior shear load of 135N | Average inlay expulsion force for prodisc® C Vivo: 349.6 ± 8.3N with 1.57 ± 0.28mm of displacement Additional expulsion testing demonstrated that the endplate geometry does not impact expulsion performance relative to the original prodisc® C implant. All acceptance criteria met | | **Subsidence** | Characterize the prodisc® C mechanical properties per static subsidence testing | Six (6) prodisc® C Vivo and six (6) prodisc® C SK specimens were placed between Grade 15 polyurethane foam blocks for an overall test height of 40mm. The testing was performed in displacement control at a rate of 6 mm/minute. Additional subsidence testing conducted on 3 prodisc® C Vivo, SK and Nova (out-of-scope) M5 devices and 3 prodisc® C Vivo, SK, Nova (out-of-scope) XLD7 devices was conducted. | Must withstand loads greater than maximum axial load that a cervical intervertebral disc can withstand (75N) | Average subsidence yield force for prodisc® C Vivo: 1081 ± 23N with an average yield displacement of 2.67 ± 0.18mm Average subsidence yield force for prodisc® C SK: 1067 ± 17N with an average yield displacement of 2.59 ± 0.13mm All acceptance criteria were met. | | **Wear** | | | | | | **Device Wear, Mode I** | Characterize the Mode I wear performance of the device | Mode I wear testing was conducted per ISO 18192-1 and/or ASTM F2423 guidelines. Four (4) prodisc® C Vivo M5 and four prodisc® C Nova XLD7 (out-of-scope) devices provided and remained lubricated at room in Hyclone Wear Test Fluid. Six (6) assemblies were subjected to 10,000,000 wear cycles at 2.0 Hz. A comparison of explanted devices to Mode I wear testing was conducted. | Wear rates to be less than the wear rate documented for total hip and knee arthroplasty, which are reported as 30 mg/million cycles and 34 mg/million cycles respectively. The wear rate should be equivalent to other cervical devices on the market (such as 1.546 ± | On average the prodisc® C Vivo M5 mass loss was 12.32 ± 2.6 mg. The average mass wear rate of the core through 10.0 MC was 1.2 ± 0.4 mg/MC for the Vivo. This corresponds to a volumetric wear rate of 1.3 ± 0.4 mm³/MC for the Vivo. MicroCT analysis demonstrates that the maximum bearing surface penetration depth is 0.4 mm. The surface roughness results confirm | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 10 of 76 {10} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | | | | 0.075mg/MC for Mobi-C) | microabrasive polishing of the articulating region of the prodisc® C Vivo M5 articulating surfaces. For the prodisc® C Vivo M5 superior endplate, the articulating surfaces increased in average surface roughness over the duration of the tests, which is also consistent with abrasion of the articulating surfaces. The comparative testing demonstrated that the Mode I Wear testing was adequate at predicting Mode I wear behavior. All acceptance criteria were met. | | **Wear, Mode III (Third Body)** | To characterize the Mode III or 3rd Body wear performance of the device | Testing was conducted to ISO 18192-1 and/or ASTM F2423 unless specified otherwise. A 5 million cycle (MC) was completed to assess the wear rate and wear mechanisms of the prodisc® C Vivo and prodisc® C Nova (out-of-scope) and changes in surface roughness to the articulating surfaces of the devices. Four (4) prodisc® C Vivo M5 and four (4) prodisc® C Nova XLD7 (out-of-scope) devices were provided, and three assemblies of each were assigned as wear test samples and one assembly was assigned as load soak control and one UHMWPE Inlay was assigned as a soak control. A comparison of explanted devices to Mode III wear testing was conducted. | The wear rate is to be less than the wear rate documented for total hip and knee arthroplasty, which are reported as 30 mg/million cycles for knee and 34 mg/million cycles for hips. The wear rate should be equivalent or greater than the wear mode I testing of prodisc® C US testing. | On average, the prodisc® C Vivo M5 mass loss was 7.5 ± 1.4 mg. The average mass wear rate of the core through 5.0 MC was 1.5 ± 0.3 mg/MC. Volumetric wear rate of 1.6 ± 0.3 mm³/MC. The maximum penetration across all wear stations experienced by the Inlay was less than 0.2mm. The comparison of in vivo retrieved and Wear Mode III (3rd Body) test prodisc® cervical devices suggests the Wear Mode III test is adequate for predicting the wear behavior under abrasive and/or 3rd Body conditions. All acceptance criteria were met. | | **Wear, Mode IV (Impingement)** | Evaluate the Mode IV, or impingement, wear | Test methods met ASTM F3295-18 guidelines unless specified otherwise. There | N/A (for characterization purposes) | After 1 million cycles, no devices demonstrated fracture, delamination, or | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 11 of 76 {11} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | | performance of the prodisc® C Nova XLD5 (out-of-scope) | were eight (8) prodisc® C Nova XLD5 (out-of-scope) constructs provided to the testing facility. One (1) assembly was assigned as load soak control, six (6) assemblies were assigned as wear test samples, and one (1) UHMWPE Inlay was assigned as a soak control. Testing was performed to 10 MC, stopping every 0.25 MC. A comparison of explanted devices to Mode IV wear testing was conducted. | | any signs of functional failure. On average the UHMWPE inlay and superior endplate (total) mass loss was 2.3 ± 0.3 mg and 0.3 ± 0.2 mg, respectively. The average mass wear rate of the inlay and superior endplate through 1.0 MC was 2.4 ± 0.3 mg/MC and 0.2 ± 0.2 mg/MC, respectively. This corresponds to a volumetric wear rate of 2.7 ± 0.3 mm³/MC for the inlay and 0.02 ± 0.02 mm³/MC for the superior endplate. The comparison of the US prodisc® C and US prodisc® C Vivo retrieved and Mode IV Wear test prodisc® cervical devices suggests the Wear Mode IV test is adequate for predicting the wear behavior under Mode IV, impingement, conditions. | | **Wear Particle Analysis** | Evaluate wear particles per ASTM F1877. | Wear fluid was assessed up to 10.0 MC (1.0, 2.5, and 10.0 MC) to analyze wear debris from the US prodisc® C Vivo and prodisc® C Nova (out-of-scope) UHMWPE inlay per ASTM F1877. | N/A (for characterization purposes) | The results of this analysis supported that the sizes and morphologies of particles found from the in vitro testing of the US prodisc® C product family are consistent with the expectations for UHMWPE on CoCrMo alloy bearing couples. | | **Dynamic Creep** | | | | | | **Dynamic Creep Relaxation** | Determine the creep characteristic of the UHMWPE inlay of the prodisc® C disc replacement | The creep relaxation test was completed by executing the normal wear Mode I testing procedure. Before and after testing, the polyethylene inlay was imaged using a μCT 80 (Scanco Medical AG, Switzerland) at a maximum voxel resolution of 18 μm | The plastic deformations should be smaller than the diurnal changes of the intervertebral disc (1.5mm). | MicroCT analysis demonstrates that the maximum bearing surface penetration depth is 0.4mm. All acceptance criteria were met. | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 12 of 76 {12} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | **Cadaver Study** | | | | | | **Low Endurance Testing** | Perform low endurance cyclic tests on the four prodisc® endplate fixation variants to assess immediate fixation | The coupled eccentric loading (CEL) protocol was used to cyclically move the specimens through a sequence of combined motions of flexion or extension with right and left axial rotation. The end limits of motion were established for load limits of 1.5 Nm in flexion, extension and axial rotation (or a combined moment of 2.1 Nm) along with a compressive load of 50 N applied to the upper mounting pot directly above the midline of the disc implant. Each specimen was cycled 2000 times and measures of implant endplate migration were made after 20 initial cycles and at cycle increments of 250, 500, 1000, 1500, and 2000. | N/A | Two segments exceeded the maximum limit of 15° during flexion but no specimens exceeded the combined sagittal plane rotation of 30°. If the alignment of the implant during the potting procedure was not parallel to the transverse plane, the end ROM could exceed the allotted maximum value of 15°. All of the specimens were under the allowable 10° of axial rotation. All but one of the of the specimen migration values were below threshold acceptance of 0.3 mm. The upper endplate of specimen 7A (original PDC) reached 0.36 mm. Referring back to the maximal failure limit of 3 mm, the mean migration values of the upper component ranged between 0.02 mm and 0.08 mm or 0.7% and 2.7% of the failure limit (3 mm), respectively, and between 0.01 mm and 0.04 mm or 0.3% and 1.3% of the failure limit (3 mm), respectively, for the lower components. Overall, no significant differences occurred between the upper endplates of any of the four implants or between any of the lower endplates of any of the four implants. | | **Shear Expulsion** | Determine the failure load required to initially fail and expulse the upper and lower endplates of | The specimens were disarticulated through the disc space and separated into upper and lower segments. Each top and bottom part of the specimen | N/A | No significant differences occurred between the four implants for any of the expulsion test data sets for Peak Expulsion force, | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 13 of 76 {13} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | | the four different prodisc® C endplate fixation variants | was individually mounted in a vice located on the base plate of the testing platform and oriented with the outer top surface of the respective implant parallel to a vertical reference plane. The gimbal assembly was programmed to move the shear tool against the implant endplate and apply a 50 N compressive load. The gimbal assembly was then programmed to move downward at a rate of 0.32 mm/s causing the shear tool to expulse the implant endplate along the path of insertion. | | Failure Initiation Work, Expulsion Work and Resistive Stiffness. No differences were found in the peak force required to expulse the implant as well as with the overall work required to initiate or completely expulse the implant. | | **MR Compatibility** | | | | | | Force Measurement | Assess the force effects on prodisc® C designs in the main static magnetic field of 3.0 Tesla | Testing was conducted per ASTM F2052. The implant was suspended with a thin string at the portal of an MR imaging unit and their deflection from the vertical was determined. | The acceptance criteria based on the MRI scanner are as follows: FDA worst case 3T scanner: 25 mT/cm field gradient, <15.5° acceptable angle Philips 1.5T: 45 mT/cm field gradient, <26.5° acceptable angle Philips 3.0T: 90 mT/cm field gradient, <30.2° acceptable angle Siemens Trio 3T: 90 mT/cm field gradient, | All implants showed low force effects far below the limit of the gravitational force of the part. All acceptance criteria were met. | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 14 of 76 {14} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | | | | <45° acceptable angle | | | Torque Measurement | Assess the torque effects on prodisc® C designs in the main static magnetic field of 3.0 Tesla | Testing was conducted per ASTM F2213. A qualitative evaluation of the torque effects was performed by manually turning the implants at the isocenter of the 3T magnet. Whenever any static torque effects could be sensed, a quantitative torque measurement was performed. | The acceptance criteria based on the MRI scanner are as follows: FDA worst case 3T scanner: 25 mT/cm field gradient, <15.5° acceptable angle Philips 1.5T: 45 mT/cm field gradient, <26.5° acceptable angle Philips 3.0T: 90 mT/cm field gradient, <30.2° acceptable angle Siemens Trio 3T: 90 mT/cm field gradient, <45° acceptable angle | No torque effects were observed with any of the implants. Therefore, no quantitative measurements according to the ASTM standards were performed. All acceptance criteria were met. | | Heating Effects | Assess the heating effects due to the Rf-field during MR-scans | Testing followed the general guidelines established in ASTM F2182. The implants were placed in the body shaped ASTM phantom filled with 30 liters of distilled water, 300g PAA and 39.6g NaCl. The conductivity of the gel was 4.8 ± 0.1mS/cm. The temperature changes were continuously measured by fiberoptic temperature probes during the 15-minute minimum time scan. | The whole- body temperature rise should not be greater than 0.5°C for normal mode and 1.0°C for controlled mode. | The temperature increase near the implant ranged from 1.1°C (1.5T) and 1.9°C (3.0T). The distribution of the increase of temperature throughout the body of the subject would result in an overall temperature increase of less than 1.0°C. All acceptance criteria were met. | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 15 of 76 {15} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Artifact Size | Estimate the artifact size around the implant | The implant was placed in a tank filled with 8L of CuSO4 solution. The part was placed on a grid and tested both orthogonally and parallel to the main magnetic field. Gradient and Spin-Echo sequences as described in ASTM 2119 were used. | N/A. The objective was to report the size of the artifact. | The maximal artifacts for the two different sequences are as follows: Implant Aligned with Magnetic Field: 1.5T Scanner, FFE: 7.0cm 1.5T Scanner, SE: 5.5cm 3.0T Scanner, FFE: 8.5cm 3.0T Scanner, SE: 6.5cm Implant Orthogonal with Magnetic Field: 1.5T Scanner, FFE: 7.0cm 1.5T Scanner, SE: 5.5cm 3.0T Scanner, FFE: 8.0cm 3.0T Scanner, SE: 6.0cm | | **Coating Characterization** | | | | | | CP Ti Plasma Spray Coating for Prodisc® Cervical Discs | Characterize the chemically pure titanium (CP Ti) plasma coating processes of the prodisc® cervical disc replacement implants | Testing was conducted per ASTM F1580, ASTM F1147, ASTM B214, ASTM F1044, ASTM F1978 | N/A | No new testing was performed as the CP Ti Coating used in the prodisc® C Vivo and prodisc® C SK are identical to the PMA-approved prodisc® C. | | **Biocompatibility/ Toxicity / Neurotoxicity** | | | | | | Implant Biocompatibility | Evaluate the biocompatibility risk of the prodisc® C implants | The biocompatibility risk assessment was conducted per ISO 10993-1, ISO 14971, and FDA General Program Memorandum #G95-1 | N/A | The prodisc® C Nova (out-of-scope), prodisc® C SK, and prodisc® C Vivo meet the requirements of ISO 10993-1, ISO 14971, and FDA General Program Memorandum #G95-1 | | Instrument Biocompatibility | Evaluate the biocompatibility risk of the prodisc® C instrumentation | The biocompatibility risk assessment was conducted per ISO 10993-1, ISO 14971, and FDA General Program Memorandum #G95-1 | N/A | The instrumentation used with the subject device were cleared for use under Traditional 510(k), K221848 | | Neurotoxicity | Assess neurologic biocompatibility of the prodisc® C implants | The wear of the articulating and non-articulating surfaces of the prodisc® C Nova (out-of-scope) were estimated using test methods in accordance with consensus standards (for Mode I Wear ASTM F2423 and ISO 18192-1, for Mode III Wear ISO 18912-1, and Mode IV Wear ASTM F3295). For the purposes of | Must be lower than a non-toxic bolus done in a human, which is described in literature as 70mg | The total estimated in vivo mass loss over 10 MC for Mode I, Mode III, and Mode IV testing were all lower than 70mg. All acceptance criteria were met. | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 16 of 76 {16} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | | | this document, the testing assessed mass loss. | | | | **Device Sterilization** | | | | | | Implant Sterilization | Validate the gamma radiation sterilization methods for the expanded family of prodisc® C SK, prodisc® C Vivo, and prodisc® C Nova (out-of-scope) | Validation testing was performed per ISO11137-2 using the VDMax^{25} sterilization dose method | Sterilization method must achieve a sterility assurance level (SAL) of 10^{-6} with 25kGy as the minimum sterilization dose | Does establishing experiment determined that 25kGy is the minimum dose required for sterilization of the prodisc® C products to achieve a SAL of 10^{-6}. All acceptance criteria were met. | | Instrument Cleaning and Sterilization | Validate the packaging, cleaning, and sterilization methods for prodisc® C instrumentation | N/A | N/A | The cleaning, sterility, packaging, and shelf-life of the Centinel Disc Instruments have been evaluated in a PMA (P070001, P070001/S019), an IDE (G190041), and most recently cleared within a traditional 510(k) (K221848). | | **Shelf Life and Transit Validation** | | | | | | Small Punch Test | Characterize the packaging and shelf-life of the prodisc® C implants | Testing was performed to ASTM F2183-02 | Average punch strength shall not decrease >20% from the time zero average | All acceptance criteria were met. | | Surface Oxidation Test | Characterize the packaging and shelf-life of the prodisc® C implants | Testing was performed to ASTM F2102-06 | No value shall exceed a SOI of 1.0 | All acceptance criteria were met. | | Residual Oxygen Test | Characterize the packaging and shelf-life of the prodisc® C implants | Testing was performed to the Fruh test method | Oxygen value ≤ 2.0% | All acceptance criteria were met. | | Leak Test | Characterize the packaging and shelf-life of the prodisc® C implants | Testing was performed to ASTM D3078 | Sterile barrier must remain undamaged | All acceptance criteria were met. | | Seal Strength Test | Characterize the packaging and shelf-life of the prodisc® C implants | Testing was performed to ASTM F88-06 | Seal strength > 1.50 lbf | All acceptance criteria were met. | | *Note, the compendium of bench testing is inclusive of the mechanical testing performed on prodisc® C SK, prodisc® C Vivo, and prodisc® C Nova (out-of-scope) which was reviewed and approved under PMA Supplement P070001/S019. The prodisc® C Nova device, which is considered out-of-scope of the subject submission, was | | | | | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 17 of 76 {17} | Test Name | Purpose | Test Method* | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | determined to be the worst-case design variant for several of the mechanical tests, which is why it is referenced in several of the tests summarized in the table above. | | | | | ## X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant conducted a clinical study to establish a reasonable assurance of safety and effectiveness of the Centinel Spine prodisc® C SK and prodisc® C Vivo devices for reconstruction of the disc from C3-C7 following discectomy at 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 radiographic 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, to treat radiculopathy/myelopathy. The study was conducted under Investigational Device Exemption (IDE) G190041 in the US. A summary of the clinical study is presented below. ### A. Study Design Subjects in the pivotal clinical trial were treated between July 2019 and December 2024. The prospective, multi-center, randomized, controlled clinical study was conducted under IDE G190041 to compare the prodisc® C SK and prodisc® C Vivo investigational devices to the Mobi-C control device, a PMA approved artificial cervical disc. The database for this PMA reflects data collected on a total of 480 subjects that were randomized and enrolled in the study; of the 480 subjects, 47 of these subjects, remained blinded, and ultimately were not treated, 433 of these subjects (N=293 prodisc® C SK and prodisc® C Vivo; and N=140 Mobi-C) had an incision time recorded. Subjects were treated at 31 US sites. Subjects in the investigational device arm could receive: treatment at two-levels with prodisc® C SK; treatment at two-levels with prodisc® C Vivo; or, treatment with a prodisc® C SK at one-level and prodisc® C Vivo at a contiguous level. It was determined that the subject device designs were similar enough to allow for different combinations in the investigational group. Subjects were randomized in a 2:1 ratio to the two-level prodisc® C SK and/or prodisc® C Vivo device (investigational group) or to the two-level Mobi-C device (control group), respectively. A statistical plan was designed to test for non-inferiority between the two groups. #### 1. Clinical Inclusion and Exclusion Criteria To be eligible for the IDE study, subjects had to meet all of the inclusion criteria and none of the exclusion criteria in **Table 3**: **Table 3: Study Inclusion and Exclusion Criteria** | Study Inclusion Criteria | Study Exclusion Criteria | | --- | --- | | In order to be eligible to participate in this study, subjects must meet all of the following criteria: 1. Male or female, age ≥18 and ≤69 years. 2. Diagnosis of radiculopathy or myeloradiculopathy of the cervical spine, with pain, paresthesia or paralysis in a specific | Subjects who meet any of the following criteria will be excluded from participating in this study: 1. Have an active systemic infection or infection at the operative site. | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 18 of 76 {18} | Study Inclusion Criteria | Study Exclusion Criteria | | --- | --- | | nerve root distribution C3 through C7, including at least one of the following: a. Neck and/or arm pain (at least 30 mm on the 100 mm visual analogue scale [VAS] scale). b. Decreased muscle strength of at least one level on the clinical evaluation 0 to 5 scale. c. Abnormal sensation including hyperesthesia or hypoesthesia; and/or d. Abnormal reflexes. 3. Symptomatic cervical disc disease (SCDD) at two contiguous levels 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: a. Decreased disc height on radiography, computed tomography (CT), or magnetic resonance imaging (MRI) in comparison to a normal adjacent disc. b. Degenerative spondylosis on CT or MRI. c. Disc herniation on CT or MRI 5. NDI Score ≥30% 6. Unresponsive to non-operative, conservative treatment (rest, heat, electrotherapy, physical therapy, chiropractic care and/or analgesics) with the following conditions: a. Approximately six weeks or more of radicular symptoms; or b. Have the presence of progressive symptoms or signs of nerve root/spinal cord compression despite continued non-operative, conservative treatment; or c. Sooner than 6 weeks for worsening symptoms of neurologic compromise. 7. Appropriate for treatment using an anterior surgical approach. 8. Reported to be medically cleared for surgery. 9. 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 | 2. Have a history of or anticipated treatment for active systemic infection, including HIV or Hepatitis C. 3. Have 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. Have previous trauma to the C3 to C7 levels resulting in significant bony or disco-ligamentous cervical spine injury. 5. Have had any prior cervical spine surgery at the operative level(s), i.e., laminotomy. 6. Have had a prior cervical TDR or fusion procedure at any level. 7. Have axial neck pain in the absence of other symptoms of radiculopathy or myeloradiculopathy justifying the need for surgical intervention. 8. Have disc height less than 3 mm as measured from the center of the disc in a neutral position. 9. Have radiographic confirmation of severe cervical facet joint disease or degeneration at any level. 10. Have osteoporosis or is at increased risk of osteoporosis, defined as a DEXA bone density measured T-score of ≤ -1.5 or worse (i.e., -1.6, -1.7, etc.). Note: A qualifying T-score from either the hip or spine may be used to confirm eligibility. For subjects without a DEXA within 24 months of screening, a score of ≥ 6 on either the SCORE (females) or MORES (males) requires a DEXA to determine eligibility. 11. Have Paget’s disease of bone, osteomalacia or any other metabolic bone disease other than osteoporosis, which is addressed above. 12. Have 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. Have Symptomatic Cervical Disc Disease or significant cervical spondylosis at three (3) or more levels. 14. Have marked cervical instability on resting (neutral) lateral or flexion-extension radiographs demonstrated by: a. Translation ≥ 3.5 mm, and/or b. Greater than 11° angular difference to that of either adjacent level | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 19 of 76 {19} | Study Inclusion Criteria | Study Exclusion Criteria | | --- | --- | | | 15. Have known allergies to cobalt, chromium, molybdenum, titanium, nickel, or polyethylene. 16. Are currently pregnant or breastfeeding at time of enrollment or have plans to become pregnant within the next three years. 17. Have rheumatoid arthritis, lupus, or other autoimmune disease that affect the musculoskeletal system. 18. Have congenital bony and/or spinal cord abnormalities that affect spinal stability. 19. Have diseases or conditions that would preclude accurate clinical evaluation (e.g. neuromuscular disorders, uncontrolled fibromyalgia). 20. Have concomitant conditions requiring daily, high-dose oral and/or inhaled steroids. High dose steroid use is defined as: a. Daily, chronic use of oral steroids equivalent to 5 mg/day of prednisone or greater. b. Daily, chronic use of inhaled corticosteroids (at least twice per day). c. Use of short-term (less than 10 days) oral steroids at a daily dose greater than 40mg prednisone equivalent within one month of the study procedure. 21. Have current or recent history (defined ≤ 1 year prior to screening) of substance abuse (alcoholism and/or narcotic addiction) requiring intervention. 22. Have a Body Mass Index (BMI) > 40 kg/m2. 23. Using any other investigational drug or medical device within the last 30 days prior to surgery. 24. Have 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. 25. 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 #21. 26. Have pending personal litigation relating to spinal injury (worker's compensation is not an exclusion). 27. Have a current history of heavy smoking (more than one pack of cigarettes per day). | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 20 of 76 {20} | Study Inclusion Criteria | Study Exclusion Criteria | | --- | --- | | | 28. Currently reside in a location, or anticipating a potential relocation, that may interfere with completion of follow-up examinations. 29. 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. 30. Have an uncontrolled seizure disorder. 31. Have had a cervical epidural steroid injection within 14 days prior to surgery | ## 2. Control Control subjects were prospectively enrolled and randomized to treatment with the Mobi-C (N=140), a PMA-approved artificial cervical disc. The Mobi-C Cervical Disc was implanted according to its surgical technique guide. ## 3. Follow-Up Schedule All subjects were evaluated pre-operatively, at treatment/discharge (prior to the subject being discharged from the hospital) and post-operatively at Week 6 (±2 weeks), Month 3 (±2 weeks), Month 6 (±1 month), Month 12 (±2 months), Month 24 (±2 months), Month 36 (±2 months) and annually thereafter (±3 months). The following parameters were measured throughout the study (Figure 2): PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 21 of 76 {21} | Procedures | Screening^{1} | Surgery (Day 0) | Day 14 (+/- 7 days) | 6 Wk (+/- 2 wks) | 3 Mo (+/- 2 wks) | 6 Mo (+/- 4 wks) | 12 Mo (+/- 8 wks) | 18 Mo^{6} (+/- 8 wks) | 24 Mo (+/- 8 wks) | 36-84 Mos (+/- 8 wks) | Unscheduled | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Informed Consent | X | - | - | - | - | - | - | - | - | - | - | | Inclusion/Exclusion Criteria | X | X | - | - | - | - | - | - | - | - | - | | Demographics | X | - | - | - | - | - | - | - | - | - | - | | Medical History | X | - | - | - | - | - | - | - | - | - | - | | Pregnancy Test | - | X | - | - | - | - | - | - | - | - | - | | MRI or CAT Scan | X | - | - | - | - | - | - | - | - | - | - | | DEXA Scan | X^{2} | - | - | - | - | - | - | - | - | - | - | | X-Ray | X | X^{5} | X | X | X | X | X | - | X | X | X^{7} | | Assessments | X^{3,4} | - | - | X^{3,4} | X^{3,4} | X^{3,4} | X^{3,4} | - | X^{3,4} | X^{3,4} | X^{3} | | Concomitant Medications | X | X | X | X | X | X | X | X | X | X | X^{7} | | Adverse Events | - | X | X | X | X | X | X | X | X | X | X^{7} | | Device Deficiencies | - | X | X | X | X | X | X | X | X | X | X^{7} | | Review Rehabilitation | - | X | X | X | X | X | X | - | X | - | X^{7} | | 1. Screening may begin up to 60 days before surgery. Refer to Section 8.2 for the screening visit procedures that should be conducted before randomization occurs. 2. DEXA required if the subject has a SCORE/MORES value ≥ 6. A new DEXA is not required if the subject had a DEXA within the 24 months prior to the screening visit. 3. Subject will complete Patient Reported Outcome questionnaires: VAS neck pain, VAS arm/shoulder pain, VAS hoarseness, Treatment Satisfaction (not at Screening), NDI Questionnaire, SF-12 Health Survey, and Dysphagia Handicap Index. These surveys should be administered prior to any other study visit assessments or procedures being performed. 4. The Investigator/designee will complete the following assessments: a physical examination, the Nurick scale, Odom's Criteria (starting at the 6 Wk. visit), and a neurological assessment. 5. Intraoperative AP and lateral radiographs/fluoroscopy should be taken prior to closure to verify proper implant positioning. 6. The 18-month visit will be completed by telephone. 7. The following procedures may be performed, if deemed necessary by the Investigator: Physical Examination, X-rays, Nurick Scale, Odom's Criteria Assessment, Neurological Assessment | | | | | | | | | | | | **Figure 2: Clinical Study Schedule of Procedures** PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 22 of 76 {22} #### 4. Clinical Endpoints The safety of the prodisc® C SK and prodisc® C Vivo at two levels was assessed by comparison to the Mobi-C control group with respect to the nature and frequency of adverse events (overall and in terms of severity and relationship to the implant), subsequent index level surgical procedures, and maintenance or improvement in neurological status. The effectiveness of the prodisc® C SK and prodisc® C Vivo at two levels was assessed by comparison to the Mobi-C control group with respect to a primary composite endpoint, as described below. Effectiveness was further evaluated by assessing improvement in the Neck Disability Index (NDI), neck and arm pain questionnaires, and quality of life using the short-form questionnaire (SF-12), as well as subject satisfaction of the prodisc® C SK and prodisc® C Vivo treatment as compared to the Mobi-C Cervical treatment. Similar criteria were used to measure success in both groups. #### Primary Endpoint The primary composite endpoint was defined as: - 15-point improvement in NDI Score (out of 100) in subjects at the Month 24 timepoint compared with baseline; - Maintenance or improvement in neurological status (motor and sensory only) at Month 24 compared to baseline; - No secondary surgical interventions (revision, removal, re-operation, supplemental fixation) at the index level(s); and, - Absence of major device-related adverse events (DRAEs) defined as radiographic failure, neurological failure, or failure by AE as adjudicated by the Clinical Events Committee (CEC). For the purpose of determining individual subject success, the subject may not experience a major AE. A major AE was defined as any of the following which are definitely related to the device system or to a device component as determined by the CEC: - No new or worsening permanent neurologic deficit; - Implant or component breakage or migration that does not require revision, reoperation or removal, but causes persistent or moderate to severe dysphagia and/or, - Subject death. PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 23 of 76 {23} Subject success was evaluated using the primary composite endpoint above at Month 24. Study success was evaluated for the Month 24 Composite Clinical Success (CCS) using the following pre-specified hypotheses pertaining to clinical non-inferiority: H₀: πT - πC <= -0.10 (the CCS rate of investigational device was clinical inferior to control) Ha: πT - πC > -0.10 (the CCS rate of investigational device was not clinical inferior to control) where πT and πC are the probabilities of achieving Month 24 CCS of the investigational and control devices, respectively. In all circumstances, non-inferiority hypotheses were based on the a priori selected non-inferiority margin, δ = -0.10. The claim of non-inferiority was pre-specified to be accepted if the posterior probability of non-inferiority, is greater than or equal to 0.967. That is, if, Pr(πT - πC > - δ | Trial Results) ≥ 0.967. This posterior probability is calculated using Beta(1, 1) non-informative priors for both the investigational arm. A Bayesian posterior probability threshold of 0.967 controls type 1 error to 0.044 with statistical power of 84.6%. Per FDA Guidance for the Preparation of IDEs for Spinal Systems (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-document-preparation-ides-spinal-systems-guidance-industry-andor-fda-staff, the following definitions applied: - Reoperation - any surgical procedure at the index level(s) that does not involve modification, addition, or removal of any components of the device in the post-operative or follow-up period. - Revision – any procedure in the post-operative or follow-up period that adjusts, modifies, or removes part of the original implant configuration with or without replacement of a component – may include adjusting the position of the original configuration in the post-operative or follow-up period. - Removal – a procedure where the entire device is removed with or without replacement of the device in the post-operative or follow-up period. - Supplemental fixation – a procedure in which additional instrumentation not under study is implanted (e.g., supplemental placement of a plate/ screw fusion system). # Secondary Endpoints The Secondary endpoints measured in both groups included: - Neck pain related disability as measured on a 100-point scale using the NDI questionnaire; - Neck pain as measured on a 100mm Visual Analog Scale (VAS) at baseline and at each follow-up time-point; - Worse arm/shoulder pain as measured separately on a 100mm VAS at baseline and at each follow-up time-point; - VAS Hoarseness on a 100mm scale at baseline and at each follow-up time-point; - Health Survey (SF-12v2) Physical Component Summary (PCS) at baseline and at each follow-up time-point (Results for MCS will be summarized); PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 24 of 76 {24} - Treatment Satisfaction; - Dysphagia Handicap Index (DHI) at Month 24 compared to baseline; - Results at Month 24 for both treatment groups as categorized by the physician according to Odom's Criteria; - Myelopathy based on the Nurick scale. A change of at least one grade at Month 24 compared to baseline will be regarded as clinically significant. In addition to the above secondary endpoints, various neurologic and radiographic (quantitative and qualitative) assessments were measured and evaluated in both groups. # 5. Clinical Events Committee A CEC was utilized for the prodisc® C SK and prodisc® C Vivo IDE study, including the Mobi-C Cervical Disc control group, to mitigate reporting bias of safety-related events. The CEC consisted of two spine surgeons and one neurosurgeon who are not affiliated with the sponsor and did not participate in the study. The CEC charter was used to define the role of the CEC. The recommendations of the CEC override the investigator's classification and become part of the clinical trial data set. The CEC adjudicated all AEs, secondary surgical interventions (SSIs), protocol deviations, and Month 24 neurological status. AEs were reviewed to confirm or re-classify the AE term, severity, seriousness, anticipated versus unanticipated, and relationship to the investigational or control devices and/or the associated procedures. For events determined to be Serious, the CEC reviewed for the potential to re-classify the event as an Unanticipated Adverse Device Effect (UADE) or not a UADE. For the events determined to be definitely related to device, the CEC determined if they qualified as a 'Major' AE, per the primary endpoint. AEs which led to SSI were reviewed to determine if the SSI met the primary endpoint criteria for SSI failure and re-classify the event as reoperation, revision, removal or supplemental fixation. Protocol deviations were classified as 'major' or 'minor'. Lastly, the CEC adjudicated neurologic status at Month 24 for all subjects to determine if neurologic status was maintained, improved, or deteriorated relative to baseline. # B. Accountability of PMA Cohort At the time of the December 31, 2024 database lock, a total of 480 subjects signed the informed consent form and were randomized (Intent-to-Treat Analysis Set): - A total of 47 subjects were randomized, remained blinded, and ultimately not treated. - A total of 46 of the 47 subjects did not meet the eligibility criteria defined in Section 7.1 and Section 7.2 of the Protocol prior to treatment. - A total of 1 of the 47 subjects was not treated because they did not meet insurance requirements. The resulting 433 available randomized subjects, with an operation date at the time of the database lock (293 prodisc® C SK and prodisc® C Vivo subjects and 140 Mobi-C control subjects) were assessed as part of the modified Intent-to-Treat (mITT) Analysis Set. Two subjects in the prodisc® C SK and prodisc® C Vivo group received fusion; therefore, the As-Treated (AT) Analysis Set includes 291 prodisc® C SK and prodisc® C Vivo subjects, and 140 Mobi-C subjects. There were PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 25 of 76 {25} a total of 25 major protocol deviations, leaving the Per Protocol (PP) Analysis Set to include 406 subjects (274 prodisc® C SK and prodisc® C Vivo subjects, and 132 Mobi-C subjects). This information is presented in tabular form in Table 4 below; similarly, this information is presented graphically via a patient accounting tree in Figure 3 below. Table 4: Accounting Information | | prodisc® C SK and prodisc® C Vivo | Mobi-C | | --- | --- | --- | | Randomized (ITT Analysis Set) | 321 | 159 | | Subjects randomized but not treated* | 28 | 19 | | mITT Analysis Set | 293 | 140 | | As Treated (AT Analysis Set) | 291 | 140 | | Number yet to reach 24 months (Day 730) as of database lock (mITT Analysis Set) | 16** | 2 | | Theoretical due (Day 730) as of database lock (mITT Analysis Set) | 277 | 138 | | Subjects with known primary outcome (CCS) at the time of database lock (mITT Analysis Set) | 253 | 127 | | Subjects with missing CCS outcome (mITT Set) | Subjects without CCS N=40 • Not yet overdue (between 730 and 790) (N=5) • Below Day 730 (N=14)** • Missing for other reasons (N=21): ○ Lost to Follow-up (N=4) ○ Death (N=2) ○ Missed 24 Month Visit (N=10) ○ Missing CCS Component (N=5) | Subjects without CCS N=13 • Not yet overdue (N=2) • Below Day 730 (N=2) • Missing for Other Reasons (N=9) ○ Withdrawn by investigator due to AE (N=1) ○ Missed 24 Month Visit (N=3) ○ Missing CCS Component (N=5) | *This includes subjects who were randomized, but not treated because they did not meet eligibility criteria per Section 7.1 and 7.2 of the Protocol. One of these subjects was withdrawn because of an issue with insurance. **The difference between Number Yet to Reach Day 730 (N=16) and subjects Below Day 730 (N=14) is two subjects (06-039, 06-040) who had an SSI before Day 730, therefore they had a known CCS outcome, and are not a subject with a missing CCS. PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 26 of 76 {26}  **Figure 3: Subject Analysis Populations** This submission includes data up to the database lock that occurred on December 31, 2024. The Month 24 CCS endpoint within the PP Analysis Set is based on 93% (342/367) of all subjects expected due. The Month 24 CCS endpoint for the mITT Analysis Set is based on 89% (348/392) of all subjects expected due. Within the mITT Analysis Set, 94.5% (277/293) of prodisc® C SK and prodisc® C Vivo subjects, and 98.6% (138/140) of Mobi-C subjects are theoretically due (Day 730); within this same analysis set, 91.3% (253/277) of prodisc® C SK and prodisc® C Vivo subjects, and 92.0% (127/138) of Mobi-C subjects have a known primary outcome. The subject accountability summary through the Month 24 timepoint is presented in **Table 5** for the mITT Analysis Set. The accounting table is stratified by treatment arm with the overall prodisc® C SK and prodisc® C Vivo group subjects referred to hereafter as the investigational group (“I”), and Control group (“C”) for subjects that have completed follow up through Month 24. PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 27 of 76 {27} Table 5: Subject Accounting Summary (mITT Population, N=433) Through Month 24 | | Pre-Op | | Treatment | | Week 06 | | Month 03 | | Month 06 | | Month 12 | | Month 24 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | I | C | I | C | I | C | I | C | I | C | I | C | I | C | | Accounting | | | | | | | | | | | | | | | | (1) Theoretical follow-up | 293 | 140 | 293 | 140 | 293 | 140 | 293 | 140 | 293 | 140 | 293 | 140 | 277 | 138 | | (2) Cumulative Death | | | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | | (3) Cumulative SSI Failures | | | 0 | 0 | 1 | 0 | 1 | 1 | 2 | 3 | 4 | 4 | 9 | 6 | | (4) Not Yet Overdue | | | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 2 | | (5) Deaths+SSI failures among theoretically due | | | 0 | 0 | 1 | 0 | 1 | 1 | 2 | 3 | 5 | 4 | 9 | 6 | | (6) Expected Due [(6)+(1)-(4)-(5)] | | | | | 292 | 140 | 292 | 139 | 291 | 137 | 288 | 136 | 262 | 130 | | (7) SSI failures among theoretically due | | | 0 | 0 | 1 | 0 | 1 | 1 | 2 | 3 | 4 | 4 | 7 | 6 | | (8) Expected due+SSI failures among theoretically Due [(8)+(6)+(7)] | | | | | 293 | 140 | 293 | 140 | 293 | 140 | 292 | 140 | 269 | 136 | | All Evaluated Accounting (Actual^{A}) Among Expected Due Procedures | | | | | | | | | | | | | | | | (9) Procedures with any clinical data in interval† | 293 | 140 | | | 272 | 134 | 279 | 135 | 280 | 136 | 277 | 130 | 243 | 121 | | (10) Visit Compliance (%) | | | | | 93% | 96% | 96% | 97% | 96% | 99% | 96% | 96% | 93% | 93% | | (11) Change in NDI | | | | | 272 | 134 | 279 | 135 | 280 | 136 | 277 | 130 | 243 | 121 | | (12) Composite Clinical Success (CCS) | | | | | | | | | | | | | 243 | 121 | | (13) Actual^{B} % Follow-up for CCS | | | | | | | | | | | | | 93% | 93% | | Within Window Accounting (Actual^{A}) Among Expected Due Procedures | | | | | | | | | | | | | | | | (14) Procedures with any clinical data in interval† | 293 | 140 | | | 263 | 132 | 224 | 111 | 243 | 121 | 269 | 125 | 233 | 116 | | (15) Visit Compliance (%) | | | | | 90% | 94% | 77% | 80% | 84% | 88% | 93% | 92% | 89% | 89% | | (16) Change in NDI | | | | | 263 | 132 | 224 | 111 | 243 | 121 | 269 | 125 | 233 | 116 | | (17) Composite Clinical Success (CCS) | | | | | | | | | | | | | 232 | 116 | | (18) Actual^{A} % Follow-up for CCS | | | | | | | | | | | | | 89% | 89% | | ^{A} Patients with complete data for each endpoint, within window. ^{B} Patients with any follow-up data reviewed or evaluated by investigator ("all evaluated" accounting). †Change in NDI. Source: Tables Follow-up Compliance mITT.sas; Analyzed: 31MAR2025 | | | | | | | | | | | | | | | PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 28 of 76 {28} ### C. Study Population Demographics and Baseline Parameters The tables below provide a summary of pre-operative and demographic variables for subjects treated in the study for both the investigational and control groups in the mITT Analysis Set. Variables summarized include age, BMI, height, and weight stratified by gender as well as race and ethnicity. Further, the demographics of the study population are typical for a cervical total disc replacement study performed in the United States. The proportions enrolled are consistent with the sex, age, racial and ethnicity of other cervical total disc replacement studies conducted to support a PMA with two-level indications in the US. Table 6: Pre-operative and Demographic Continuous Variables (mITT Analysis, N=433) | | prodisc® C | | | | | | Mobi-C | | | | | | Group Difference* | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | Δ | LB | UB | p | | All | | | | | | | | | | | | | | | | | | Age (years) | 293 | 49.4 | 8.8 | 50.0 | 22.6 | 69.5 | 140 | 48.7 | 9.1 | 47.9 | 29.1 | 69.0 | 0.7 | -1.0 | 2.5 | 0.448 | | BMI (kg/m²) | 292 | 29.2 | 4.8 | 29.2 | 17.7 | 40.6 | 140 | 28.4 | 4.5 | 28.2 | 18.5 | 39.8 | 0.9 | 0.0 | 1.8 | 0.069 | | Height (inches) | 292 | 67.7 | 3.9 | 68.0 | 58.0 | 76.0 | 140 | 67.9 | 4.0 | 68.0 | 55.0 | 78.0 | -0.2 | -1.0 | 0.6 | 0.647 | | Weight (lbs) | 292 | 191.5 | 37.9 | 190.0 | 103.0 | 275.0 | 140 | 186.8 | 36.8 | 182.3 | 118.0 | 284.0 | 4.7 | -2.5 | 12.1 | 0.225 | | Female | | | | | | | | | | | | | | | | | | Age (years) | 146 | 48.9 | 8.4 | 48.8 | 22.6 | 66.9 | 66 | 47.9 | 9.2 | 46.6 | 29.1 | 68.4 | 1.0 | -1.3 | 3.6 | 0.422 | | BMI (kg/m²) | 145 | 28.6 | 5.5 | 28.1 | 17.7 | 40.6 | 66 | 27.5 | 5.1 | 26.9 | 18.5 | 39.8 | 1.1 | -0.4 | 2.6 | 0.194 | | Height (inches) | 145 | 64.7 | 2.7 | 65.0 | 58.0 | 71.0 | 66 | 64.9 | 2.7 | 65.0 | 55.0 | 70.0 | -0.1 | -0.9 | 0.6 | 0.716 | | Weight (lbs) | 145 | 170.0 | 33.3 | 167.6 | 103.0 | 270.0 | 66 | 164.4 | 30.6 | 159.5 | 118.0 | 239.0 | 5.6 | -3.3 | 15.1 | 0.254 | | Male | | | | | | | | | | | | | | | | | | Age (years) | 147 | 49.8 | 9.1 | 52.0 | 26.6 | 69.5 | 74 | 49.3 | 8.9 | 49.6 | 31.4 | 69.0 | 0.4 | -2.0 | 2.9 | 0.740 | | BMI (kg/m²) | 147 | 29.9 | 3.9 | 29.5 | 23.0 | 39.5 | 74 | 29.1 | 3.7 | 29.1 | 20.8 | 39.0 | 0.8 | -0.2 | 1.9 | 0.143 | | Height (inches) | 147 | 70.7 | 2.4 | 70.5 | 63.0 | 76.0 | 74 | 70.6 | 2.8 | 70.5 | 63.0 | 78.0 | 0.1 | -0.6 | 0.8 | 0.861 | | Weight (lbs) | 147 | 212.7 | 29.3 | 210.0 | 135.0 | 275.0 | 74 | 206.7 | 29.9 | 203.0 | 155.0 | 284.0 | 6.0 | -1.8 | 14.2 | 0.156 | | Clinical Scores | | | | | | | | | | | | | | | | | | Neck Disability Index (NDI) | 293 | 58.9 | 15.8 | 58.0 | 30.0 | 100.0 | 140 | 57.2 | 15.9 | 56.0 | 28.0 | 96.0 | 1.7 | -1.3 | 4.8 | 0.305 | | VAS Back | 293 | 73.8 | 18.7 | 77.0 | 2.0 | 100.0 | 140 | 74.3 | 17.4 | 77.0 | 0.0 | 100.0 | -0.5 | -4.0 | 3.1 | 0.786 | | VAS Hoarseness | 293 | 19.0 | 25.9 | 5.0 | 0.0 | 100.0 | 140 | 19.5 | 27.2 | 4.0 | 0.0 | 100.0 | -0.6 | -5.6 | 4.7 | 0.827 | | VAS Left Arm/Shoulder | 293 | 53.2 | 34.0 | 60.0 | 0.0 | 100.0 | 140 | 52.5 | 35.4 | 63.0 | 0.0 | 100.0 | 0.8 | -5.8 | 7.6 | 0.828 | | VAS Right Arm/Shoulder | 293 | 52.0 | 33.4 | 59.0 | 0.0 | 100.0 | 140 | 54.1 | 33.2 | 66.5 | 0.0 | 100.0 | -2.0 | -8.4 | 4.6 | 0.546 | Table 7: Pre-operative and Demographic Categorical Variables (mITT Analysis, N=433) | | prodisc® C | | | Mobi-c | | | p* | | --- | --- | --- | --- | --- | --- | --- | --- | | | N | n | % | N | n | % | | | Race | | | | | | | | | Black or African American | 293 | 17 | 5.8% | 140 | 3 | 2.1% | 0.242 | | Native Hawaiian or Other Pacific Islander | | 2 | 0.7% | | 0 | 0.0% | | | Asian | | 1 | 0.3% | | 2 | 1.4% | | | White | | 265 | 90.4% | | 131 | 93.6% | | | Other | | 8 | 2.7% | | 4 | 2.9% | | | Ethnicity | | | | | | | | | Hispanic or Latino | 293 | 14 | 4.8% | 140 | 9 | 6.4% | 0.496 | | Not Hispanic or Latino | | 279 | 95.2% | | 131 | 93.6% | | The tables below provide a summary of intraoperative surgical variables for subjects treated in the study for both the investigational and control groups in the AT Analysis Set, and mITT Analysis Set. Variables summarized include operative time, blood loss, and length of stay. There was a difference in blood loss, in favor of Mobi-C. It is important to note that this difference is expected as Mobi-C does not require a keel cut during implantation. Furthermore, the keel cut into the PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 29 of 76 {29} cancellous bone, which is required during implantation of prodisc® C SK, will create more bone bleeding than should be seen on average with prodisc® C Vivo or Mobi-C. **Table 8: Summary of Continuous Intra-Operative Variables (mITT Analysis, N=433)** | | prodisc® C | | | | | | Mobi-C | | | | | | Group Difference* | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | N | Mean | SD | Med | Min | Max | N | Mean | SD | Med | Min | Max | Δ | LB | UB | p | | **All** | | | | | | | | | | | | | | | | | | Operative Time (minutes) | 293 | 104.1 | 38.0 | 97.0 | 35.0 | 241.0 | 140 | 102.5 | 38.1 | 97.0 | 42.0 | 214.0 | 1.6 | -5.7 | 9.1 | 0.697 | | Length of Stay (days) | 293 | 0.5 | 0.8 | 0.0 | 0.0 | 9.0 | 140 | 0.5 | 0.6 | 0.5 | 0.0 | 4.0 | 0.0 | -0.2 | 0.1 | 0.642 | | Blood Loss (cc) | 293 | 33.6 | 30.5 | 25.0 | 5.0 | 200.0 | 140 | 26.7 | 17.9 | 25.0 | 5.0 | 100.0 | 7.0 | 1.8 | 12.3 | 0.013 | | *Device group mean differences and 95% Credible Intervals. Nominal Two-sided t-test p-value (equal variance). Source: Tables Intra-Op mITT.sas; Analyzed: 17MAR2025 | | | | | | | | | | | | | | | | | As demonstrated above, the investigational subjects and control subjects that make up the mITT analysis population are not significantly different with respect to baseline variables. Intra-operative data differed only for blood loss, with the control group reporting a lower mean amount (p = 0.013) than the investigational group. ## **D. Study Results** ### **1. Safety Results** #### *Adverse Event Summary* The CEC reviewed all safety events for both treatment groups, including AEs and SSIs, to allow for uniform adjudication of study-related events and evaluations and to eliminate any site-by-site variations in reporting. Specifically, the CEC reviewed and adjudicated AE category, severity, procedure and implant-relatedness, seriousness, and if serious, whether or not the event was anticipated. **Table 9** shows a summary of AE categories and rates between the investigational and control groups in the ITT Analysis Set. Overall, similar rates of AEs occurred in the investigational group (78.5% - 252/321) and control group (78.6% - 125/159). SAEs that were considered “definitely” device-related were also comparable between the two groups, where 1.6% (5/321) of investigational subjects had “definitely” device-related SAEs, while 1.9% (3/159) control of subjects had “definitely” device-related SAEs. Lastly, the rate of SAEs that were considered “definitely” procedure-related was 3.1% (10/321) in investigational subjects and 1.9% (3/159) in control subjects. PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 30 of 76 {30} **Table 9: Adverse Event Summary (ITT Analysis Set, N=480)** | | prodisc® C (N= 321) | | | Mobi-C (N= 159) | | | prodisc® C - Mobi-C | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Events | n | % | Events | n | % | Δ | LB^{3} | UB^{3} | p-value^{4} | | **Adverse Events (AE)** | | | | | | | | | | | | All | 832 | 252 | 78.5% | 354 | 125 | 78.6% | -0.1% | -7.9% | 7.7% | 0.999 | | Device Related^{1} | 153 | 123 | 38.3% | 82 | 65 | 40.9% | -2.6% | -11.9% | 6.7% | 0.620 | | Device Related - Definitely | 9 | 8 | 2.5% | 4 | 4 | 2.5% | 0.0% | -3.0% | 2.9% | 0.999 | | Procedure Related^{2} | 252 | 158 | 49.2% | 124 | 78 | 49.1% | 0.2% | -9.3% | 9.7% | 0.999 | | Procedure Related - Definitely | 41 | 35 | 10.9% | 21 | 17 | 10.7% | 0.2% | -5.7% | 6.1% | 0.999 | | **Serious Adverse Events (SAE)** | | | | | | | | | | | | All | 72 | 60 | 18.7% | 31 | 28 | 17.6% | 1.1% | -6.2% | 8.4% | 0.803 | | Device Related^{1} | 10 | 9 | 2.8% | 7 | 7 | 4.4% | -1.6% | -5.3% | 2.1% | 0.419 | | Device Related - Definitely | 6 | 5 | 1.6% | 3 | 3 | 1.9% | -0.3% | -2.8% | 2.2% | 0.724 | | Procedure Related^{2} | 19 | 17 | 5.3% | 9 | 9 | 5.7% | -0.4% | -4.7% | 4.0% | 0.834 | | Procedure Related - Definitely | 10 | 10 | 3.1% | 3 | 3 | 1.9% | 1.2% | -1.6% | 4.1% | 0.559 | | **AE by Severity** | | | | | | | | | | | | Mild | 485 | 202 | 62.9% | 204 | 90 | 56.6% | 6.3% | -3.0% | 15.7% | 0.197 | | Moderate | 261 | 137 | 42.7% | 107 | 73 | 45.9% | -3.2% | -12.7% | 6.2% | 0.558 | | Severe | 86 | 70 | 21.8% | 43 | 36 | 22.6% | -0.8% | -8.8% | 7.1% | 0.907 | | **SAE by Severity** | | | | | | | | | | | | Mild | 1 | 1 | 0.3% | 1 | 1 | 0.6% | -0.3% | -1.7% | 1.1% | 0.553 | | Moderate | 7 | 7 | 2.2% | 6 | 6 | 3.8% | -1.6% | -5.0% | 1.8% | 0.372 | | Severe | 64 | 54 | 16.8% | 24 | 23 | 14.5% | 2.4% | -4.5% | 9.2% | 0.597 | | **Death** | | | | | | | | | | | | All | 2 | 2 | 0.6% | 0 | 0 | 0.0% | 0.6% | -0.2% | 1.5% | 0.999 | | NA=Not applicable. | | | | | | | | | | | | ^{1}Device related is anything that was possibly, probably or definitely related to the device. | | | | | | | | | | | | ^{2}Procedure related is anything that was possibly, probably or definitely related to the procedure. | | | | | | | | | | | | ^{3}95% Exact unconditional confidence intervals. | | | | | | | | | | | | ^{4}Fisher's exact test. | | | | | | | | | | | | Source: Tables AE Summary ITT.sas; Analyzed: 01APR2025 | | | | | | | | | | | ### All Adverse Events **Table 10** lists all AEs reported as of the database lock by AE term, with the number of subjects experiencing the events. Percentages are calculated as the number of subjects experiencing an event divided by the number of subjects treated in the ITT Analysis Set. The investigational group presented with 832 events occurring in 78.5% (252/321) of the 321 prodisc® subjects, compared to 354 events occurring in 78.6% (125/159) of the 125 Mobi-C control subjects. The most common AEs (rate of 5% or more) included: dysphagia (investigational – 7.8%, 25/321; control – 8.8%, 14/159); general disorders and administrative site conditions – Covid-19 (investigational – 9.3%, 30/321; control – 8.2%, 13/159); joint pain (investigational – 11.5%, 37/321; control – 13.2%, 21/159); spasms (investigational – 7.5%, 24/321; control – 4.4%, 7/159); other musculoskeletal pain (investigational – 6.2%, 20/321; control – 6.9%, 11/159); numbness/tingling (investigational – 7.2%, 23/321; control – 5.7%, 9/159); radiculopathy (investigational – 21.5%, 69/321; control – 23.9%, 38/159); and trauma (investigational – 10.0%, 32/321; control – 11.9%, 19/159). PMA P070001/S025: FDA Summary of Safety and Effectiveness Data Page 31 of 76 {31} **Table 10: All Adverse Events (ITT Analysis Set N=480)** | | prodisc® C (N= 321) | | | Mobi C (N= 159) | | | Group Difference^{1} | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Events | Subs | %* | Events | Subs | %* | Δ | LB | UB | | **All** | **832** | **252** | **78.5%** | **354** | **125** | **78.6%** | **-0.1%** | **-7.9%** | **7.7%** | | **Blood and Lymphatic System Disorders** | **9** | **9** | **2.8%** | **2** | **2** | **1.3%** | **1.5%** | **-1.3%** | **4.4%** | | Anemia | 3 | 3 | 0.9% | 1 | 1 | 0.6% | 0.3% | -1.4% | 2.0% | | Blood Clots (non-pulmonary) | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Other Blood and Lymphatic System Disorders | 5 | 5 | 1.6% | 1 | 1 | 0.6% | 0.9% | -1.2% | 3.0% | | | prodisc® C (N= 321) | | | Mobi C (N= 159) | | | Group Difference^{1} | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Events | Subs | %* | Events | Subs | %* | Δ | LB | UB | | **Cardiac Disorders** | **8** | **8** | **2.5%** | **4** | **4** | **2.5%** | **0.0%** | **-3.0%** | **2.9%** | | Acute Coronary Syndrome | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Atrial Fibrillation | 0 | 0 | 0.0% | 1 | 1 | 0.6% | -0.6% | -1.5% | 0.2% | | Chest Pain | 2 | 2 | 0.6% | 1 | 1 | 0.6% | 0.0% | -1.5% | 1.5% | | Myocardial Infarction | 2 | 2 | 0.6% | 0 | 0 | 0.0% | 0.6% | -0.6% | 1.8% | | Syncope/Fainting | 2 | 2 | 0.6% | 1 | 1 | 0.6% | 0.0% | -1.5% | 1.5% | | Ventricular Arrhythmia | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Other Cardiac Disorders | 0 | 0 | 0.0% | 1 | 1 | 0.6% | -0.6% | -1.5% | 0.2% | | **Ear and Labyrinth Disorders** | **6** | **6** | **1.9%** | **3** | **2** | **1.3%** | **0.6%** | **-1.8%** | **3.0%** | | Ear Pain | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Impaired Hearing | 2 | 2 | 0.6% | 0 | 0 | 0.0% | 0.6% | -0.6% | 1.8% | | Vertigo | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Other Ear and Labyrinth Disorders | 2 | 2 | 0.6% | 3 | 2 | 1.3% | -0.6% | -2.4% | 1.1% | | **Endocrine Disorders** | **11** | **9** | **2.8%** | **4** | **3** | **1.9%** | **0.9%** | **-2.1%** | **3.9%** | | Diabetes Mellitus | 6 | 6 | 1.9% | 1 | 1 | 0.6% | 1.2% | -1.0% | 3.5% | | Hypothyroidism | 2 | 2 | 0.6% | 2 | 2 | 1.3% | -0.6% | -2.4% | 1.1% | | Hyperlipidemia | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Other Endocrine Disorder | 2 | 2 | 0.6% | 1 | 1 | 0.6% | 0.0% | -1.5% | 1.5% | | **Eye Disorders** | **8** | **6** | **1.9%** | **2** | **2** | **1.3%** | **0.6%** | **-1.8%** | **3.0%** | | Blurred Vision | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Cataract | 3 | 2 | 0.6% | 1 | 1 | 0.6% | 0.0% | -1.5% | 1.5% | | Dry Eye | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Glaucoma | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Retinal Detachment | 0 | 0 | 0.0% | 1 | 1 | 0.6% | -0.6% | -1.5% | 0.2% | | Other Eye Disorders | 2 | 2 | 0.6% | 0 | 0 | 0.0% | 0.6% | -0.6% | 1.8% | | **Gastrointestinal Disorders** | **60** | **47** | **14.6%** | **32** | **26** | **16.4%** | **-1.7%** | **-8.5%** | **5.1%** | | Constipation | 1 | 1 | 0.3% | 1 | 1 | 0.6% | -0.3% | -1.5% | 0.9% | | Diarrhea | 1 | 1 | 0.3% | 0 | 0 | 0.0% | 0.3% | -0.6% | 1.2% | | Dyspepsia | 3 | 3 | 0.9% | 1 | 1 | 0.6% | 0.3% | -1.4% | 2.0% | | Dysphagia | 26 | 25 | 7.8% | 14 | 14 | 8.8% | -1.0% | -6.2% | 4.2% | | Gastroesophageal Reflux Disease | 8 | 8 | 2.5% | 1 | 1 | 0.6% | 1.9% | -0.7% | 4.4% | | Hemorrhage | 0 | 0 | 0.0% | 1 | 1 | 0.6% | -0.6% | -…