Synergy Disc

P250028 · Synergy Spine Solutions, Inc. · MJO · Feb 26, 2026 · Orthopedic

Device Facts

Record IDP250028
Device NameSynergy Disc
ApplicantSynergy Spine Solutions, Inc.
Product CodeMJO · Orthopedic
Decision DateFeb 26, 2026
DecisionAPPR
Device ClassClass 3
AttributesTherapeutic

Intended Use

The Synergy Disc 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 Synergy Disc 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 Synergy Disc.

Device Story

Synergy Disc is a three-piece cervical artificial disc prosthesis; consists of superior/inferior titanium alloy endplates (plasma-sprayed) and UHMWPE core. Designed to replace degenerated native discs; restores motion/balance to cervical spinal unit. Implanted via anterior approach by spine surgeons. Semi-constrained design allows flexion-extension, lateral bending, axial rotation, and translation. Provides motion preservation as alternative to fusion (ACDF). Clinical benefit includes reduction in neck/arm pain and improved functional disability scores (NDI).

Clinical Evidence

Prospective, multi-center, non-randomized, historically controlled clinical study (IDE G180090) comparing Synergy Disc (n=177) to ACDF historical control (n=192). Primary endpoint: Month 24 Composite Clinical Success (CCS). Synergy Disc demonstrated non-inferiority and superiority to ACDF control. CCS rate: 87.1% (Synergy) vs 56.6% (ACDF). Synergy group showed greater NDI improvement (91.0% vs 72.1%) and lower device-related SAE rate (2.8% vs 10.9%).

Technological Characteristics

Three-piece prosthesis; titanium alloy endplates with commercially pure titanium plasma spray coating; UHMWPE core. Semi-constrained kinematics. Available in multiple footprints (12-18mm A/P x 15-19mm Lateral), heights (5-7mm), and lordotic angles (0°, 6°). Sterilized via Ethylene Oxide (EO). MR compatible (3.0T).

Indications for Use

Indicated for skeletally mature patients with single-level cervical (C3-C7) disc disease (radiculopathy or myelopathy) confirmed by imaging (herniated nucleus pulposus, spondylosis, or disc height loss) who failed 6 weeks of conservative treatment. Contraindicated in patients with tumor, trauma, multi-level disease, implant material allergy, bridging osteophytes, radiographic instability, facet degeneration, active infection, or osteoporosis (T-score ≤ -2.5).

Reference Devices

Related Devices

Submission Summary (Full Text)

{0} SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) I. GENERAL INFORMATION Device Generic Name: Artificial Cervical Disc Device Trade Name: Synergy Disc Device Product Code: MJO Applicant’s Name/Address: Synergy Spine Solutions Inc. 357 S. McCaslin Blvd., Suite 120 Louisville, CO 80027 Date of Panel Recommendation: None Premarket Approval Application: P250028 (PMA Number) Date of FDA Notice of Approval: February 26, 2026 II. INDICATIONS FOR USE The Synergy Disc 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 Synergy Disc 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 Synergy Disc. III. CONTRAINDICATIONS Synergy Disc should not be implanted in patients with the following conditions: - Tumor or trauma - Intractable radiculopathy or myelopathy necessitating surgical treatment at more than one cervical level - Allergy or sensitivity to the implant materials (e.g., titanium and polyethylene) - Bridging osteophytes - Radiographic instability on lateral, coronal or flexion / extension radiographs: translation greater than 3.5mm and/or greater than 11 degrees of angular difference from either adjacent segments - Facet joint degeneration - Active systemic or local infection - Osteoporosis defined as Dual-Energy X-ray Absorptiometry (DEXA) bone mineral density T-score less than -2.5 P250028: FDA Summary of Safety and Effectiveness Data 1 of 66 {1} - Advanced cervical spine conditions or diseases at the index level other than those included in the Indications for Use (e.g., rheumatoid arthritis, Diffuse Idiopathic Skeletal Hyperostosis (DISH), ankylosing spondylitis) # IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the Synergy Disc labeling. # V. DEVICE DESCRIPTION The Synergy Disc is a three-piece cervical artificial disc manufactured from titanium alloy and Ultra-high-molecular-weight-polyethylene (UHMWPE). As shown in Figure 1, the three components of the Synergy Disc include a superior titanium alloy endplate, an UHMWPE core, and an inferior titanium alloy endplate. The titanium alloy endplates are coated with commercially pure titanium plasma spray. ![img-0.jpeg](img-0.jpeg) Figure 1: Schematic of Synergy Disc (left), Exploded Schematic of the Synergy Disc (right) The Synergy Disc is an intervertebral disc prosthesis designed to restore motion and balance to the intervertebral segment of the cervical spine when replacing a degenerated native disc. The Synergy Disc is designed to restore and maintain the natural behavior of a functional spinal unit by maintaining motion and balance, which are inherent to the properties of the native disc. The Synergy Disc is a cervical artificial disc manufactured from titanium alloy endplates and a UHMWPE core. As shown in Figure 2, flexion-extension, lateral bending, axial rotation, and translation are all semi-constrained. P250028: FDA Summary of Safety and Effectiveness Data {2} ![img-1.jpeg](img-1.jpeg) $20^{\circ} - 22^{\circ}$ Flexion-Extension ![img-2.jpeg](img-2.jpeg) 2mm A-P Translation ![img-3.jpeg](img-3.jpeg) $\pm 12^{\circ}$ Lateral Bending ![img-4.jpeg](img-4.jpeg) $\pm 12^{\circ}$ Axial Rotation Figure 2: Synergy Disc Targeted Ranges of Motion The Synergy Disc is available in the sizes shown below in Table 1. Table 1: Synergy Disc Part Listing and Size Overview | Footprint Size | Disc Height | Lordotic Angle | Reference Number | | --- | --- | --- | --- | | Extra Small (12mm A/P x 15mm Lateral) | 5mm | 0° | 1077-3050 | | | 5mm | 6° | 1077-3056 | | | 6mm | 0° | 1077-3060 | | | 6mm | 6° | 1077-3066 | | | 7mm | 6° | 1077-3076 | | Small (14mm A/P x 15mm Lateral) | 5mm | 0° | 1077-3150 | | | 5mm | 6° | 1077-3156 | | | 6mm | 0° | 1077-3160 | | | 6mm | 6° | 1077-3166 | | | 7mm | 6° | 1077-3176 | | Small-Wide (14mm A/P x 17mm Lateral) | 5mm | 0° | 1077-3450 | | | 5mm | 6° | 1077-3456 | | | 6mm | 0° | 1077-3460 | | | 6mm | 6° | 1077-3466 | | | 7mm | 6° | 1077-3476 | | Medium (16mm A/P x 17mm Lateral) | 5mm | 0° | 1077-3250 | | | 5mm | 6° | 1077-3256 | | | 6mm | 0° | 1077-3260 | | | 6mm | 6° | 1077-3266 | | | 7mm | 6° | 1077-3276 | | Medium-Wide (16mm A/P x 19mm Lateral) | 5mm | 0° | 1077-3550 | | | 5mm | 6° | 1077-3556 | | | 6mm | 0° | 1077-3560 | | | 6mm | 6° | 1077-3566 | | | 7mm | 6° | 1077-3576 | | Large (18mm A/P x 19mm Lateral) | 5mm | 0° | 1077-3350 | | | 5mm | 6° | 1077-3356 | | | 6mm | 0° | 1077-3360 | | | 6mm | 6° | 1077-3366 | | | 7mm | 6° | 1077-3376 | P250028: FDA Summary of Safety and Effectiveness Data {3} VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several other alternatives for the 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. These alternative treatments are summarized below: - Nonoperative alternative treatments, which include, but are not limited to, simple neck adjustments, physical therapy, traction, heat, medications, braces, chiropractic care, bed rest, 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 using intervertebral cages, with various bone grafting techniques, with or without supplemental anterior plating - Decompression with posterior spinal systems (e.g., rods, hooks, wires) - Another FDA-approved artificial cervical disc Each option has advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle. VII. MARKETING HISTORY The Synergy Disc received CE mark in 2013. It is currently distributed in the European Union, United Kingdom, Australia, Switzerland, Malaysia, South Africa, and Canada via Special Access. The Synergy Disc has 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 Synergy Disc clinical study results, approved device labeling for other cervical total disc replacement (cTDR) devices, and published scientific literature including: (1) those associated with any general surgical procedure; (2) those associated with anterior cervical spine surgery; and (3) those associated with a cervical artificial disc device, including the Synergy Disc. In addition to the risks listed below, there is also the risk that surgery may not be effective in relieving symptoms or may cause worsening of symptoms. Additional surgery may be required to correct some of the adverse effects. General Surgery Risks General surgical risks include, but are not limited to: - Abscess - Superficial (shallow) infection - Deep wound infection - Pneumonia (lung infection) - Atelectasis (collapsed lung) - Septicemia (blood poisoning) - Edema - Hematoma - Injury to blood vessels - Soft tissue damage - Nerve or muscular damage - Phlebitis (inflammation of the blood vessel in your leg) or P250028: FDA Summary of Safety and Effectiveness Data {4} thromboembolus (blood clot in the legs) - Pulmonary embolism (blood clot in the lung) - Hemorrhage (excessive bleeding) - Respiratory distress or depression (slow, shallow, or difficulty breathing) - Pulmonary edema (abnormal collection of fluid in the lungs) - Thromboembolism (blood clot in the vessel) - Reactions to the drugs or anesthesia used during and after surgery - Reactions to blood transfusions - Failure of the tissue to heal properly (e.g., hematoma [a pocket of blood caused by bleeding from a broken blood vessel]; wound dehiscence [failure of the incision to completely heal which may allow it to reopen]), cellulitis, or wound necrosis, which may require drainage, aspiration (removing a substance using suction), debridement (surgery to clean foreign material and dead tissue out of a wound), or other treatment - Pain at the incision - Complications of unknown pregnancy including miscarriage and fetal birth defects - Inability to resume activities of daily living - Myocardial infarction (heart attack) - Stroke - Seizure, convulsion, or change in mental status - Death ## Anterior Cervical Surgery Risks Anterior cervical surgical risks include, but are not limited to: - Damage to nerves that may result in changes in the sensation and/or muscle weakness in your neck, legs, arms, and/or shoulders - Paralysis (loss of ability to move muscles with the loss of feeling also) - Paresthesia (a sensation of pricking, tingling, or creeping on the skin) - Dysphagia (trouble swallowing) - Dysphonia (trouble with the voice or speaking) - Hoarseness - Dysarthria (difficulty articulating speech that is otherwise linguistically normal) - Vocal cord paralysis - Laryngeal palsy - Sore throat - Recurring aspirations (inhaling foreign substances into the lungs) - Fistula (an abnormal passage) - Tracheal, esophageal, and/or pharyngeal perforation (penetration of the windpipe, the tube that goes from the throat to the stomach, and/or the area between the mouth and esophagus that performs the swallowing action) - Airway obstruction (blockage of the airway) - Spinal stenosis (narrowing of the nerve passages that go from the spine to the rest of your body) - Hardening or tearing of the tissue surrounding the implant - Spondylosis - Worsening of the degenerative disc disease condition at adjacent levels - Discitis (inflammation of the disc), Arachnoiditis (inflammation of middle layer of the tissues that cover the spinal cord), or other types of inflammation P250028: FDA Summary of Safety and Effectiveness Data {5} - External chylorrhea - Damage to nerves, blood vessels, and nearby tissues including, for example, muscle and/or ligament injury - Dural tear or leak - Epidural bleeding (bleeding around the membrane covering the tissue surrounding your spinal cord that may require a blood transfusion or another operation) - Epidural hematoma (a pocket of blood caused by a broken blood vessel or bone bleeding in the membrane covering the nerves or the tissues surrounding your spinal cord) - Epidural fibrosis (scar tissue formation on the membrane covering the nerves) - Instability of the operated or adjacent vertebrae - Blindness by prolonged pressure on the eye during the operation - Urinary or fecal incontinence - Surgery at the wrong level of your spine - Loss of bone around the implant (osteolysis related to debris from implant wear) - Injury to the spinal cord or the nerves leaving or entering the spinal cord - Disc herniation (“slipped disc”) - Loss of disc height - Injury of the membrane (dura) surrounding the spinal nerves which may or may not result in leakage of spinal fluid - Impaired muscle or nerve function (symptoms like clumsiness, numbness, foot drop, neurological weakness, etc.) - Fracture of the vertebra, spinous process (the part of your spine that you can feel through the skin on your back), or other damage to bony structures during or after surgery - Deterioration of the facet joints in the adjacent vertebrae (worsening of the condition) - Postoperative muscle and tissue pain - The chance that the surgery will not reduce the pain or symptoms felt before the surgery - Failure of the fusion to heal - Spontaneous fusion (unplanned, self-generated fusion of the vertebra) - The spine may undergo unfavorable changes or deterioration at the operated level(s) and/or the levels above and below including loss of proper spinal curvature, correction, height, and/or reduction, or malalignment, which may require another surgery ## Cervical Artificial Disc Risks Risks specific to cervical artificial discs, including the Synergy Disc, include, but are not limited to: - Airway obstruction - Wear debris generation - Foreign body (allergic) reaction to implant materials (titanium alloy, UHMWPE) - Metallosis - Staining - Tumor formation - Autoimmune disease - Early or late loosening of the components; disassembly - Bending or breakage of any or all of the components - Implant subsidence (the implant may sink into the bone) - Loss of fixation; sizing issues with components - Anatomical or technical difficulties - Bone fracture P250028: FDA Summary of Safety and Effectiveness Data {6} - Scarring - Bone resorption - Bone formation (including heterotopic ossification (HO)) 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 - Need for subsequent surgical intervention - An unfavorable reaction where the bone and the implant meet - Possible pain, infection, and permanent damage to the bone or surrounding tissues at the site where bone graft was taken - Implant migration or malposition, (the implant could be improperly positioned) either peri-operatively or post-operatively - Adverse reaction or foreign body reaction to implant materials (possible allergic reaction to the metal) or there may be some wearing of the implant material against bone or another part of the implant that creates very small particles; it is possible that these particles may eventually cause the local tissues such as bone, nerves and nearby soft tissue to respond badly - Placement of the study device at the wrong level of the spine - Implant may become loose, deform (permanently change shape), fail, break, wear out, or move which may require another surgery to correct the problem and/or remove the implant - Instruments used to insert the implant may break or malfunction in use which may cause damage to the surgical site or surrounding tissues - Pain, discomfort, and/or abnormal sensations caused by the presence of the implant - Implanting the incorrect size may cause the device to be less effective or safe - Surgery may be converted to Anterior Cervical Discectomy and Fusion (ACDF) if poor visualization at the index level due to anatomical limitations P250028: FDA Summary of Safety and Effectiveness Data 7 of 66 {7} These conditions do not include all potential adverse events (AEs) that may occur, but are important considerations in relation to the use of the Synergy Disc. For the specific AEs that occurred in the Synergy Disc clinical study, please see Section X. ## IX. SUMMARY OF NON-CLINICAL STUDIES A variety of testing was conducted to characterize the performance of the Synergy Disc, including: - Static Axial Compression - Dynamic Axial Compression - Static Compression Shear - Dynamic Compression Shear - Static Torsion - Device Expulsion - Device Subsidence - Device Creep - Pristine Wear Testing (Mode I Wear) - Abrasive (Third Body) Wear Testing (Mode III Wear) - Impingement Wear Testing (Mode IV Wear) - Range of Motion (ROM) - Coating Assessment - Biocompatibility/Toxicity - Neurotoxicity - Device Sterilization/Packaging - MR Compatibility Table 2: Non-Clinical Study Summary | Test Name | Purpose | Test Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Static and Dynamic Strength | | | | | | Static Axial Compression | Verify static performance under simulated physiologic conditions is sufficient to withstand in vivo compressive loads | ASTM F2346 | A minimum of 200 N in axial compression | Maximum compression: 0.80mm at 3449N. | | Dynamic Axial Compression | Verify dynamic performance under simulated physiologic conditions is sufficient to withstand in vivo compressive loads | ASTM F2346 | The implant must survive a fatigue test to 10 million cycles with a 100 N axial compression load | Dynamic strength ≥ 400N Change in disc height (max): 0.12mm At Runout 10 million cycles. | | Static Compression Shear | Verify static performance under simulated | ASTM F2346 | The implant should withstand at | Static shear yield load: 978N Compressive shear stiffness: 943 N/mm | P250028: FDA Summary of Safety and Effectiveness Data {8} | Test Name | Purpose | Test Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | | physiologic conditions is sufficient to withstand in vivo compressive shear loads | | least 120 N in compression shear | | | Dynamic Compression Shear | Verify dynamic performance under simulated physiologic conditions is sufficient to withstand in vivo compressive shear loads | ASTM F2346 | The implant must survive a fatigue test to 10 million cycles with a 100 N compression shear load | Dynamic shear load: ≥1000N. Change in disc height (max): 0.28mm. | | Static Torsion | Verify that the static torsion performance is sufficient to withstand anticipated in vivo torsional loads | ASTM F2346 | N/A for characterization purposes | Static torsional yield torque: 0.40Nm. Torsional stiffness: 0.039Nm/degree. | | Expulsion | | | | | | Expulsion | Verify ability of Synergy Disc to resist expulsion using simulated physiologic conditions | Synergy Discs implanted in foam blocks with 100N axial preload were subjected to anterior shear at a rate of 6 mm/min. Monotonic loading was applied to both endplates in the posterior to anterior direction. | Implant should resist at least 80 N in anterior expulsion and posterior migration | Synergy Disc was able to withstand an expulsion force of 104N. Results verify device will remain stable under in vivo shear loading conditions. | | Subsidence | | | | | | Subsidence | Verify the ability of the Synergy Disc to resist subsidence using simulated physiologic conditions | ASTM F2267 | Subsidence yield load required for 1mm plastic deformation should be greater than the 200 N axial compression | Kp value of the Synergy Disc (597N/mm). | | Creep | | | | | | Implant Creep | Evaluate the creep properties of the Synergy Disc. | Three (3) Synergy Disc devices were | | Mean core creep was significantly less than the | P250028: FDA Summary of Safety and Effectiveness Data 9 of 66 {9} | Test Name | Purpose | Test Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | | | tested in implant creep. | Implant Creep with 100 N axial compression load cannot exceed 0.5mm over 60 days | natural creep of the healthy native cervical disc. | | Wear | | | | | P250028: FDA Summary of Safety and Effectiveness Data 10 of 66 {10} | Test Name | Purpose | Test Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Pristine Wear Testing (Mode-I) | To determine the wear and durability characteristics of the Synergy Disc under complex physiologic conditions (Mode-I). | Two 10,000,000 cycles wear tests (based on ISO 18192-1 and ASTM F2423) were performed on six (6) ‘Large’ Synergy Disc test specimens. Specimens were subjected to combined ±7.5° flexion/extension, ±6°axial rotation, and ±6° lateral bending while submerged in bovine serum solution with a protein concentration of 30 g/L. One test was performed at 2.0 Hz with a 100 N axial load, and the second at 1.0 Hz with a 50-150 N axial load. Two (2) test specimens served as load soak controls. Wear particulate was collected at 1.0, 5.0, and 10.0 million cycle (MC) intervals, the 10Mc sample was analyzed via electron microscopy and low angle laser light scattering under ASTM F1877-05. | The implant must have an average total wear of less than 56mg during wear debris testing to 10 million cycles | 8.1mg of total wear during 10MC. Average gravimetric wear rate at 2.0 Hz (100 N): 0.78 mg/MC. Average gravimetric wear rate at 1.0 Hz (150 N): 0.9 mg/MC. No devices demonstrated signs of fracture or functional failure. Wear particle analysis showed size distributions and morphology in ranges consistent with other well-tolerated spinal and orthopaedic devices. All acceptance criteria were met. | P250028: FDA Summary of Safety and Effectiveness Data 11 of 66 {11} | Test Name | Purpose | Test Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Abrasive Wear Testing (Mode-III) | To characterize in vitro wear properties under third-body abrasive wear conditions (Mode III) | Testing based on ISO 18192-1 and ASTM F2423. Specimens were subjected to combined ±7.5° flexion/extension, ±6°axial rotation, and ±6° lateral bending while submerged in third-body titanium particle slurry bovine serum lubricant. Testing was performed at 1.0 Hz with a 50-150 N applied load. | N/A, for characterization purposes | Mean mass wear rates – - Superior Endplate: 0.1 mg/MC at 1MC, 0.0 mg/MC at 5MC - Polyethylene Core: 3.5 mg/MC at 1MC, 2.0 mg/MC at 5MC - Inferior Endplate: 0.1 mg/MC at 1MC, 0.0 mg/MC at 5MC. Average scratch height of 4.7μm in the superior endplates and 2.7μm on the inferior endplates. Average penetration of 0.2 ± 0.0 mm for the wear stations and had a penetration measurement range of 0.0 mm to 0.1 mm for the load soak stations after 5.0 MC. No measurable penetration on the articulating surfaces of the superior and inferior endplates following 5.0 MC of testing. Particle analysis shows size distributions and morphology in ranges consistent with other spine/ortho devices. No devices demonstrated signs of fracture or functional failure. | P250028: FDA Summary of Safety and Effectiveness Data 12 of 66 {12} | Test Name | Purpose | Test Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Impingement Wear Testing (Mode-IV) | To characterize the wear and durability of the Synergy Disc under simulated endplate-to-endplate impingement wear (Mode-IV). | Testing based on ASTM F3295-18, (ISO 18192-1, -3, and ASTM F2423-11 as guides) Three (3) ‘Large’ and three (3) ‘Small’ sized Synergy Disc were subjected to 1 x 10^{6} cycles of combined 300 N axial load, 10^{°}-26^{°} extension, and ±6^{°} axial rotation at 1 Hz per ASTM F3295-18 while submerged in bovine serum solution with a protein concentration of 30 g/L. Two (2) test specimens, one per size, served as load soak controls. Wear particulate was collected and analyzed via electron microscopy and low angle laser light scattering under ASTM F1877-05. | N/A (for characterization purposes) | Gravimetric wear rates: Size Small: 0.5 mg/Mc Size Large: 0.6 mg/Mc No devices demonstrated signs of fracture or functional failure. | P250028: FDA Summary of Safety and Effectiveness Data 13 of 66 {13} | Test Name | Purpose | Test Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Range of Motion (ROM) | Characterize ROM of Synergy Disc using finite element techniques. | N/A | Similar in character and magnitude to the natural model | The kinematic analysis shows that ROM kinematics of the single level total disc replacement (TDR) implanted at either the C4-C5 or C5-C6 levels is similar in character and magnitude to the natural model and experiments in flexion, lateral bending and axial rotation. | | Coating | | | | | | Coating Assessment | Coating assessment provided. | ASTM F1580, ASTM F1147, ASTM F1044, ASTM F1160, ASTM F1854, ASTM F1978 | N/A | Coating specifications and mechanical performance passed standardized criteria. | | Biocompatibility/ Toxicity | | | | | | Cytotoxicity | Evaluate the cytotoxicity of the Synergy Disc | ISO 10993-5 | Less than or equal to mild cellular reactivity (Grade ≤ 2) | Pass. | | Sensitization | Evaluate the biological safety of the Synergy Disc | ISO 10993-1, ISO 14971 | N/A | Pass. Utilizing the established biological safety of a device with identical materials and manufacturing, the subject device is determined to be biocompatible. | | Irritation | | | | | | Acute Systemic Toxicity | | | | | | Material-Mediated Pyrogenicity | | | | | | Subacute/Subchronic Systemic Toxicity | | | | | | Genotoxicity | | | | | | Implantation | | | | | | Chronic Systemic Toxicity | | | | | | Carcinogenicity | | | | | | Neurotoxicity | | | | | | Neurotoxicity | Assess neurologic biocompatibility by evaluating the wear debris collected during Mode I wear testing (10 MC) | ASTM F2423 ISO 18192-1 | The implant must have an average total wear of less than 56mg during wear debris, derived from Cunningham et al. | Pass. | | Device Sterilization/Packaging | | | | | P250028: FDA Summary of Safety and Effectiveness Data 14 of 66 {14} | Test Name | Purpose | Test Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Sterilization Validation | Validate sterility of Synergy Disc Ethylene Oxide (EO) sterilization method | ANSI/AAMI/ISO 11135:2014 | Sterility assurance level (SAL) of 10^{-6} | EO sterilization validated to achieve a minimum sterility assurance level (SAL) of 10^{-6} of the Synergy Disc. | | Ethylene Oxide Residuals | Validate EO residuals following sterilization are below standardized limits to minimize exposure to the patient. | ISO 10993-7 | EO residuals must be at or below levels specified in ISO 10993-7: EO TCL < 10 μg/cm^{2} | Pass. | | Pyrogenicity (Bacterial Endotoxins) | Validate bacterial endotoxins are below a pre-established safety limit of 20 EU/device | ANSI/AMSI ST7; USP <85> | < 20.0 EU/device | Pass. | | Packaging Validation | Validate the packaging strength and integrity to maintain a sterile barrier through transport and the stated shelf life | ISO 11607, ASTM D4169 | -Devices should not be visibly damaged. -Sterile barrier must remain intact -Seal strength is ≥ 0.96PLI (pounds per a linear inch) | Passing results on real time and accelerated aged to support a 5-year shelf life. | | MR Compatibility | | | | | | Induced Displacement Force | Evaluate magnetically induced displacement force under MRI at 3.0T | ASTM F2052 | Angular displacement is ≤ 45° Calculated maximum allowable spatial gradient is ≥ 19 T/m | Induced force is substantially less than gravity. | | Induced Torque | Evaluate magnetically induced torque under MRI at 3.0T | ASTM F2213 | Minimal to no torque effects relative to gravity | MR-induced torque is substantially less than gravity. | | Induced Heating | Evaluate radio frequency (RF) induced heating under MRI at 1.5 T and 3.0T | ASTM F2182 | Less than 6°C over 15 minutes of scanning at a whole body console specific | MR-induced heating is ≤2.5°C at 1.5T and ≤4.0°C at 3.0T. | P250028: FDA Summary of Safety and Effectiveness Data {15} | Test Name | Purpose | Test Method | Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | | | | absorption rate (SAR) of 2.0 W/kg or greater | | | MRI Artifact | Evaluate MRI-induced artifact under MRI at 1.5 T and 3.0 T | ASTM F2119 | N/A | The maximum MR-induced artifact is 1.7cm using slice thickness of 3T. | ## X. SUMMARY OF PRIMARY CLINICAL STUDIES The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of the Synergy Disc 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 study was performed in the United States (US) under IDE G180090 with anterior cervical discectomy and fusion (ACDF) historical control data from a separate IDE study performed in the US (IDE G040081). A summary of the clinical study is presented below. ## A. Study Design Subjects in the Synergy Disc group of the pivotal clinical trial were treated between January 2021 and May 2023. The prospective, multi-center, non-randomized, historically controlled clinical study was conducted under IDE. The Synergy Disc database for this PMA reflects data collected through May 12, 2025, and includes 177 subjects enrolled across 20 sites. The Synergy Disc group results were compared to historical control data, non-concurrently enrolled, from the ACDF control group of the NuVasive Porous Coated Motion (PCM) Artificial Cervical Disc IDE study (G040081). An observational study design using propensity score (PS) subclassification was used to demonstrate covariate balance and enhance the quality of inferences regarding effectiveness and safety relative to ACDF control. The PS-selected control cohort included 192 subjects. The resultant PS-selected study cohort used for the pre-specified primary analysis population thus included all Synergy Disc subjects and historical control subjects (no PS-trimmed subjects were identified. Completers within the pre-specified primary analysis population are also analyzed. ### 1. Clinical Inclusion and Exclusion Criteria To be eligible for the Synergy Disc IDE study, subjects had to be eligible for a fusion procedure and meet all of the inclusion criteria and none of the exclusion criteria in Table 3: P250028: FDA Summary of Safety and Effectiveness Data {16} Table 3: Study Inclusion/Exclusion Criteria | Study Inclusion Criteria | Study Exclusion Criteria | | --- | --- | | 1) Age 18-70 years; | 1) Infection at the site of surgery; | | 2) Diagnosis of radiculopathy or myelopathy of the cervical spine, with either radiculopathy symptoms – pain, paresthesia, or paralysis in a specific nerve root distribution C4, C5, C6, or C7, including at least one of the following: | 2) History of, or anticipated treatment for, active systemic infections, including HIV infection or hepatitis C; | | a) Arm/shoulder pain (at least 30 mm on 100 mm VAS scale); | 3) Prior attempted or completed cervical spine surgery, except (1) laminoforaminotomy (greater than 6 months prior to scheduled surgical treatment), which includes removal of disc material necessary to perform a nerve root decompression, with less than one-third facetectomy at any level, (2) a successful single-level anterior cervical fusion (greater than 6 months prior to scheduled surgical treatment); | | b) Decreased muscle strength of at least one level on the 0-5 scale described below: | 4) More than one immobile vertebral level between C1-T1 from any cause, including but not limited to congenital abnormalities, osteoarthritic “spontaneous” fusions, and prior cervical spinal fusions; | | i) Abnormal sensation, including hyperesthesia or hypoesthesia; And/or abnormal reflexes; Or myelopathy symptoms including positive Romberg evaluation, abnormal heel/toe walk, pathologic hyperreflexia or clonus in lower extremity, positive Babinski, or positive Hoffman’s; | 5) Previous trauma to the C3-T1 levels resulting in significant bony or disco-ligamentous cervical spine injury; | | 3) Symptomatic at only one level from C3-C4 to C6-C7; | 6) Axial neck pain in the absence of other symptoms of radiculopathy or myelopathy justifying the need for surgical intervention; | | 4) Radiographically determined pathology at level to be treated correlating to primary symptoms, including at least one of the following: | 7) Radiographic confirmation of severe facet joint disease or degeneration; | | a) Decreased disc height compared to adjacent levels on radiographic film, CT, or MRI | 8) Osteoporosis: A screening questionnaire for osteoporosis, SCORE (Simple Calculated Osteoporosis Risk Estimation) for females or MORES (Male Osteoporosis Risk Estimation Score), will be used to screen patients to determine those patients who require a hip/spine DXA, a bone mineral density measurement. A SCORE or MORES ≥ 6 requires a DXA. If DXA is required, exclusion will be defined as a DXA bone density measured T score ≤ -2.5 (The World Health Organization definition of osteoporosis). DXA scans within the last 6 months prior to surgical treatment may be used; | | b) Degenerative spondylosis on CT or MRI | 9) Paget’s disease, osteomalacia, or any other metabolic bone disease (excluding osteoporosis which is addressed above); | | c) Disc herniation on CT or MRI | 10) Severe diabetes mellitus requiring daily insulin management; | | 5) Neck Disability Index (NDI) Score ≥ 30/100; | 11) Active malignancy: a history of any invasive malignancy (except non-melanoma skin cancer), unless the patient has been treated with curative intent and there have been no clinical signs or symptoms of the malignancy for at least 5 years; | | 6) Unresponsive to non-operative treatment for six weeks, or has presence of progressive symptoms or signs of nerve root/spinal cord compression in the face of conservative treatment; | 12) Tumor as a source of symptoms; | | 7) Appropriate for treatment using an anterior surgical approach, including having no more than one previous anterior surgical approach to the cervical spine; | 13) Symptomatic DDD or significant cervical spondylosis at two or more levels; | | 8) Ability and willingness to comply with follow-up regimen; and | 14) Marked cervical instability on resting lateral or flexion/extension radiographs demonstrated by: | | 9) Written informed consent given by subject | a) Translation > 3.5 mm and/or | P250028: FDA Summary of Safety and Effectiveness Data 17 of 66 {17} | Study Inclusion Criteria | Study Exclusion Criteria | | --- | --- | | | b) >11° angular difference to that of either adjacent level; 15) Known or suspected allergy to cobalt, chromium, molybdenum, titanium alloy or polyethylene 16) Severe myelopathy to the extent that the patient is wheelchair bound; 17) Congenital canal stenosis resulting in a canal diameter of < 10 mm, as measured by CT or MRI; 18) Kyphotic segmental angulation of greater than 11 degrees at treatment or adjacent levels; 19) Arachnoiditis; 20) Pregnant (verified in patients of childbearing potential by a negative urine pregnancy test when preadmission testing is obtained), or interested in becoming pregnant during the duration of the study; 21) Autoimmune disorders that impact the musculoskeletal system (e.g., lupus, rheumatoid arthritis; ankylosing spondylitis); 22) Congenital bony and/or spinal cord abnormalities that affect spinal stability; 23) Spinal axis disease (thoracic or lumbar) to the extent that surgical consideration is likely anticipated within 6 months after the cervical procedure; 24) Other degenerative joint disease (e.g. shoulder, hip, knee) to the extent that surgical consideration is likely anticipated within 6 months after the cervical procedure; 25) Diseases or conditions that would preclude accurate clinical evaluation (e.g. neuromuscular disorders such as diffuse idiopathic skeletal hyperostosis (DISH)); 26) Medications that could interfere with fusion or other bone/soft tissue healing (e.g. anticipated continued use of systemic steroid medication postoperatively); 27) Currently experiencing acute episode of major mental illness (psychosis, major affective disorder, or schizophrenia), or manifesting physical symptoms without a diagnosable medical condition to account for the symptoms, which may indicate symptoms of psychological rather than physical origin; 28) Current or recent history of substance (drug or alcohol) per site PI’s determination; 29) Morbid obesity, defined as body max index (“BMI”) > 40 or more than 100 lbs. over ideal body weight; 30) Currently using, or planning to use, bone growth stimulators in the cervical spine; 31) Use of any other investigational drug or medical device within the last 30 days prior to surgery; 32) Currently a prisoner; 33) Currently pursuing personal litigation (defined as litigation that will likely influence the patient’s | P250028: FDA Summary of Safety and Effectiveness Data 18 of 66 {18} | Study Inclusion Criteria | Study Exclusion Criteria | | --- | --- | | | ability or willingness to accurately report their treatment outcomes) related to the neck or cervical spine injury; however, involvement in worker’s compensation related litigation is not a required exclusion. | ## 2. Control As mentioned above, a historical control study design was used with control subjects obtained from the ACDF cohort of a previously completed multi-center, prospective, randomized non-inferiority clinical trial, for the NuVasive PCM Artificial Cervical Disc IDE study (G040081). A detailed comparison of the indications, inclusion/exclusion criteria, and study outcomes of the historical ACDF cohort and the Synergy Disc IDE study protocol concluded that this dataset is an appropriate comparator to support this PMA application. A PS methodology was applied to address potential selection bias when combining historical control data with the prospectively enrolled investigational cohort. Historical control subjects were selected to achieve similarity in baseline covariates with Synergy Disc subjects within PS subclasses. Statistical and graphical balance assessments demonstrated that Synergy Disc subjects and PS-selected controls had comparable multivariate baseline covariate distributions within PS subclasses. ## 3. Follow-up Schedule All subjects were evaluated pre-operatively, at treatment, and post-operatively at the immediate post-operative visit (up to 21 days post-treatment), and at Week 6 (± 14 days), Month 3 (± 2 weeks), Month 6 (± 2 months), Month 12 (± 2 months), Month 24 (± 2 months) and annually thereafter (± 2 months) until the last subject enrolled had completed Month 24 evaluation. The following parameters were measured throughout the study (Table 4): P250028: FDA Summary of Safety and Effectiveness Data 19 of 66 {19} Table 4: Synergy Disc IDE Study Assessment Schedule | VISIT | Enrollment/Preoperative16 | Surgery Day 0 | Immediate Post-Op (7-21 days) | 6-Wk (42 days) ± 14 days | 3-Months (90 days) ± 14 days | 6-Months (180 days) ± 60 days | 12-Months (365 days) ± 60 days | 24-Months (730 days) ± 60 days | Annually Thereafter ± 60 days | Unscheduled | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Informed Consent Process | X | - | - | - | - | - | - | - | - | - | | Inclusion/Exclusion Criteria | X | X | - | - | - | - | - | - | - | - | | Demographics | X | - | - | - | - | - | - | - | - | - | | Medical History | X | - | - | - | - | - | - | - | - | - | | Pregnancy test | - | X | - | - | - | - | - | - | - | - | | MRI or CAT Scan | X | - | - | - | - | - | - | - | - | - | | Hip DEXA Scan | X2 | - | - | - | - | - | - | - | - | - | | X-Ray | X3,7 | X6 | X1 | X1 | X7 | X7 | X7 | X7 | X7 | X7 | | Assessments9 | X4,5 | - | - | X4,5 | X4,5 | X4,5 | X4,5 | X4,5 | X4,5 | X4,5 | | Record/Review Concomitant Medications | X | - | X | X | X | X | X | X | X | X | | Record/Review Adverse Events | - | X | X | X | X | X | X | X | X | X | | Record/Review Device Deficiencies | - | X | X | X | X | X | X | X | X | X | | Review Rehabilitation8 | - | - | X | X | X | - | - | - | - | X | | 1No flexion/extension x-ray immediate post-op or 6-wk.2DEXA bone mineral density will be recorded when dictated by osteoporosis screening (SCORE or MORES).3DDD pathology will be confirmed by MRI or CAT Scan.4Patient will complete self-assessment tools: neck pain, arm/shoulder pain (VAS); Patient Satisfaction (not conducted at baseline); NDI Questionnaire, SF-36 Health Survey, and Dysphagia Assessment (Bazaz, Hoarseness Scale)5The Investigator will complete the following assessments: physical examination, Nurick/Odom's Criteria, Subject Survey and Neurological Assessment. (*Odom's Criteria will only be assessed post-operatively.)6Intraoperative AP and lateral radiographs should be taken prior to closure to verify proper implant positioning.7Anteroposterior, upright neutral lateral and flexion-extension lateral films must be taken at this visit for all patients.8Rehabilitation can be marked as completed at 3 month visit or continue if necessary per investigator discretion.9The subject reported surveys should be administered prior to any other study visit assessments or procedures being performed to prevent information from the examination biasing the subject's responses.10Enrollment/Preoperative clinical evaluation will occur within 60 days of Surgery. MRI and CAT Scans can be conducted within 6 months of Surgery. X-Rays can be conducted within 3 months of Surgery | | | | | | | | | | | # 4. Clinical Endpoints The safety of the Synergy Disc was assessed by comparison to the historical ACDF control group with respect to the nature and frequency of AEs (overall and in terms of seriousness, severity, and relationship to the device or procedure), additional index level surgical procedures and maintenance or improvement in neurological status. The effectiveness of the Synergy Disc was assessed by comparison to the historical ACDF 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/shoulder pain based on a Visual Analog Scale (VAS), and quality of life using the short-form questionnaire P250028: FDA Summary of Safety and Effectiveness Data {20} (SF-36), as well as patient satisfaction of the Synergy Disc group compared to the historical ACDF Control group. Similar criteria were used to measure success in both groups. ## Primary Endpoint The study hypothesis was that in subjects with DDD defined as 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 at one level from C3 to C7 that is unresponsive to conservative management, the Month 24 composite clinical success (CCS) rate of the Synergy Disc would be non-inferior as compared to the historical ACDF control subjects at Month 24. If non-inferiority was determined, the hypothesis that the investigational device is superior to the ACDF control was also tested. The primary endpoint for the Synergy Disc subjects required the subject to meet all of the following criteria at 24 months: - At least a 15-point improvement in NDI Score (out of 100) at Month 24 compared to baseline; - Maintenance or improvement in neurologic status (motor and sensory only) at Month 24 compared to baseline; - No study failures due to secondary surgical interventions (revision, removal, reoperation, and/or supplemental fixation) at the index level; - Absence of radiographic failure, defined as any implant or component breakage or migration at the index level; and, - Absence of device-related serious adverse events (SAEs) as adjudicated by the Clinical Events Committee (CEC). Similarly, the primary endpoint for the historical ACDF control group subjects was defined as: - At least a 15-point improvement in NDI Score (out of 100) at Month 24 compared to baseline; - Maintenance or improvement in neurologic status at Month 24 compared to baseline; - No study failures due to secondary surgical interventions (revision, removal, reoperation, and/or supplemental fixation) at the index level; - Fusion occurred; and, - Absence of device-related SAEs through Month 24. Device failure is defined as breakage, migration, or mechanical failure of the components. For purpose of determining individual subject success, a SAE is defined as any of the following which are definitely related to the device system or to a device component as determined by the CEC: - Permanent neurologic damage or permanent nerve root injury related to a level at or below the level treated; - 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. P250028: FDA Summary of Safety and Effectiveness Data 21 of 66 {21} For the ACDF control group, the same components of the CCS were employed, with the exception that non-fusion was an indicator of overall clinical failure. For the purpose of evaluating whether a fusion has occurred, the following criteria were applied to the ACDF control cohort: - Translational motion less than or equal to 3 mm; - Angular motion less than or equal to 2 degrees; and, - Bridging bone; - Radiolucent lines around less than 50% of the assembly. Per the 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 apply: - Reoperation - any surgical procedure at the index level that does not involve modification, addition or removal of any components of the device in the postoperative or follow-up period. - Revision - any procedure in the postoperative 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 postoperative or follow-up period. - Removal - a procedure where the entire device is removed with or without replacement of the device in the postoperative or follow-up period. - Supplemental fixation – a procedure in which additional instrumentation not under study is implanted (e.g., supplemental placement of a rod/ screw system). ## Secondary Endpoints The secondary endpoints included: - Clinically significant improvement in one or more radicular symptoms or myelopathy at Month 24 compared to baseline for each group. The data collected reflect the number of subjects who improved (numbers were stratified to reflect clinical improvement), remain unchanged, and deteriorated at each study time point. These endpoints were graded and defined as follows: - Time to recovery (time to first 15-point NDI improvement) - A visual analog scale (VAS) was used to evaluate each of the following pain locations: - Neck pain; - Left arm/shoulder pain; - Right arm/shoulder pain; - Worse Arm/Shoulder pain; - Hoarseness - SF-36 at baseline and at each follow-up time-point; - Bazaz Dysphagia Score at Month 24 compared to baseline; - Results categorized according to Odom’s Criteria; - Patient Satisfaction; - Myelopathy based on the Nurick scale; P250028: FDA Summary of Safety and Effectiveness Data 22 of 66 {22} In addition to the primary and secondary objectives listed above, various neurologic, operative, and radiographic (quantitative and qualitative) assessments were measured and evaluated. ## 5. Analysis Populations The study defined the following populations for analysis: - Intent-to-Treat (ITT) Analysis Set: The ITT analysis set will include all enrolled subjects, regardless of whether or not that treatment was actually received/completed. A subject must be selected into a PS subclass in order to be included in the ITT analysis set. - As Treated (AT) Analysis Set: The AT analysis set includes those subjects in which treatment was actually completed with either the Investigational device or the Control device. - Per-Protocol (PP) Analysis Set: The Per Protocol analysis set will consist of the subset of the AT analysis set with no major protocol violations as determined by the independent CEC, including important violations of inclusion or exclusion criteria and other post-surgical protocol violations expected to have substantial impact on the likelihood of interpreting Month 24 composite clinical success. The Per Protocol Set will be used for primary analysis, as is conservative for a test of non-inferiority. The Intention-to-Treat Set will be used to confirm these results. - Safety Analysis Set: The safety analysis set included all subjects in the ITT analysis set. ## 6. Clinical Events Committees An independent CEC, comprised of three spine surgeons who are not affiliated with the sponsor and did not participate in the study, reviewed all AEs including the appropriate AE term/code and category, relationship to the device and/or procedure, seriousness, and severity. In addition, the CEC adjudicated protocol deviations to determine which deviations were considered major or minor. The recommendation of the CEC overrode the investigator's classification and became part of the clinical trial data set. The CEC also 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 Table 5 below presents subject accounting and Figure 3 presents the subject accounting tree for all subjects within the study. A total of 369 subjects (177 investigational subjects; 192 control subjects) comprised the Intent-to-Treat (ITT) Analysis Set. - Two (2) subjects in the Synergy Disc group were enrolled but not treated with the Synergy Disc. Seven (7) subjects in the ACDF control group were enrolled but not treated, including one (1) subject removed from the study intra-operatively for additional treatment. The resulting 175 Synergy Disc subjects and 184 ACDF Control subjects comprised the As-Treated (AT) Analysis Set. - Eleven (11) Synergy Disc and twenty-eight (28) ACDF control subjects had a major protocol deviation, resulting in 164 investigational subjects and 156 ACDF control subjects in the Per-Protocol (PP) Analysis Set. P250028: FDA Summary of Safety and Effectiveness Data 23 of 66 {23} Table 5: Subject Accounting | | Synergy Disc | Control | | --- | --- | --- | | Enrolled (ITT Analysis Set) | 177 | 192 | | Treated (AT Analysis Set) | 175 (2 Synergy subjects were enrolled but not treated with the Synergy Disc) | 184 (7 subjects not treated; 1 subject removed from study intraoperatively due to additional treatment required) | | Per Protocol (PP) Analysis Set | 164 (11 Synergy subjects had a Major Protocol Deviation) | 156 (28 Control subjects had a Major Protocol Deviation) | | # of Subjects (PP Analysis Set) yet to reach 24 Months (Day 730) as of Database Lock | 5* | 0 | | Theoretical Due (PP Analysis Set) (Day 730) as of Database Lock | 159 | 156 | | Subjects with Complete Primary Outcome Data (PP Analysis Set) | 155 | 136 | | Reasons for Missing Primary Outcome • Not yet overdue (Have not reached Day 790) • Below day 730 • Missing for other reasons (Withdrawal, loss to follow up etc.) | 9 subjects missing at least 1 component of CCS • 5 subjects missed the 24 Month Visit (> Day 790) • 1 subject was withdrawn from the study at 12 Months by site because subject did not return for visits • 3 subjects missing at least one component of primary endpoint | 20 subjects missing at least 1 component of the CCS | | *Subjects had yet to reach Day 730 at time of Database Lock but completed their Month-24 visit before the Database Lock. Subject data is included in the Per Protocol analysis set. | | | P250028: FDA Summary of Safety and Effectiveness Data {24} ![img-5.jpeg](img-5.jpeg) Figure 3: Subject Accounting Tree # C. Study Population Demographics and Baseline Parameters Table 6 provides a summary of pre-operative and demographic variables for subjects in the ITT Analysis Set for both the investigational and control groups. The demographics of the study population are typical for a cTDR study performed in the US. Table 6: Pre-Operative and Demographic Variables (ITT Analysis Set) | | Synergy Disc (N=177) | | | | | Control (N=192) | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Description | n | Mean | S.D. | Median | Min, Max | n | Mean | S.D. | Median | Min, Max | | Age (years) | 177 | 46.1 | 9.8 | 45 | 23.0, 70.0 | 192 | 43.6 | 8.6 | 44 | 19.0, 63.0 | | Height (in) | 177 | 67.7 | 4.3 | 68 | 58.0, 77.0 | 191 | 67.4 | 3.8 | 67 | 58.0, 75.0 | | Weight (lbs) | 177 | 189.4 | 39.6 | 185 | 110.2, 297.0 | 191 | 176.8 | 38.7 | 177 | 100.0, 295.0 | | BMI (kg/m2) | 177 | 29.0 | 4.9 | 28.6 | 18.9, 39.7 | 192 | 27.2 | 4.9 | 26 | 19.0, 41.0 | Table 7 identifies categorical demographic information for investigational and control subjects in the ITT Analysis Set. The proportions enrolled are consistent with the sex, age, racial and ethnicity of other cTDR studies conducted to support a PMA with one-level indications in the US. The table also presents information on the number of subjects with prior cervical fusion. P250028: FDA Summary of Safety and Effectiveness Data {25} Table 7: Categorical Demographic Information (ITT Analysis Population) | Description | Synergy Disc (N=177) | | Control (N=192) | | | --- | --- | --- | --- | --- | | | n | % | n | % | | Sex | | | | | | Male | 94 | 53.1 | 100 | 52.1 | | Female | 83 | 46.9 | 92 | 47.9 | | Race* | | | | | | Black or African American | 7 | 4 | 7 | 3.6 | | Native Hawaiian or Other Pacific Islander | 1 | 0.6 | 0 | 0 | | Asian | 4 | 2.3 | 5 | 2.6 | | White | 165 | 93.2 | 176 | 91.7 | | American Indian or Alaska Native | 0 | 0 | 0 | 0 | | Other | 3 | 1.7 | 4 | 2.1 | | Ethnicity | | | | | | Hispanic or Latino | 11 | 6.2 | 0 | 0 | | Not Hispanic or Latino | 166 | 93.8 | 0 | 0 | | Missing | 0 | 0 | 192 | 100 | | Educational Status | | | | | | Some high school | 5 | 2.8 | 8 | 4.2 | | High school graduate | 19 | 10.7 | 44 | 22.9 | | Some college | 62 | 35 | 76 | 39.6 | | Complete bachelor's degree | 56 | 31.6 | 31 | 16.1 | | Some graduate work | 3 | 1.7 | 3 | 1.6 | | Completed graduate degree (MBA, MD, PhD) | 32 | 18.1 | 30 | 15.6 | | Prior cervical Fusion | 18 | 10.2 | 22 | 11.5 | | N = Total number of subjects n = Number of subjects in each category *More than one can be selected | | | | | ## D. Intra-Operative Data Table 8 provides a summary of intra-operative variables for investigational and control subjects in the ITT Analysis Set. In the investigational group, the mean surgery time was 66.5 minutes as compared to a mean surgery time of 85.7 minutes in the control group. The mean estimated blood loss in the investigational group was 21.4 cc as compared to a mean estimated blood loss of 57.9 cc in the control group. Please note, if a subject was discharged on the same day as surgery, that would count as 1 day for length of stay. If discharge is the following day, the length of stay would be 2. The exact times of discharge are not available. Therefore, the 1.3 mean length of stay is not indicative of a length of stay of 31 hours. Table 8: Intra-Operative Variables (ITT Analysis Set) | Description | Synergy Disc (N=177) | | | | | Control (N=192) | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | n | Mean | S.D. | Median | Min, Max | n | Mean | S.D. | Median | Min, Max | | Surgery time (min) | 177 | 66.5 | 25.1 | 62 | 28.0, 153.0 | 184 | 85.7 | 40.5 | 72 | 23.0, 258.0 | | Estimated blood loss (cc) | 175 | 21.4 | 17.5 | 20 | 0.0, 150.0 | 184 | 57.9 | 46.2 | 50 | 0.0, 325.0 | | Length of hospital stay (days) | 175 | 1.3 | 0.5 | 1 | 1.0, 4.0 | 184 | 2.4 | 0.7 | 2 | 1.0, 7.0 | ## E. Safety and Effectiveness Results ### 1. Safety Results #### Adverse Events Summary The CEC reviewed all safety events through Month 24 for both the Synergy Disc and ACDF Control group including AEs and subsequent surgical interventions (SSIs). This allowed for uniform resolution of study-related events and evaluations and eliminated any site-by-site P250028: FDA Summary of Safety and Effectiveness Data {26} variations in reporting. The same AE code list and relationship definitions were applied to both the investigational and control groups by the CEC. All safety tables presented below include the following data: - $\mathrm{N} =$ total number of subjects - $n =$ total number of subjects in category - $m =$ number of mentions (events) in each category - $\% =$ total number of subjects in each category divided by total number of subjects (n/N) Table 9 identifies a summary of AE categories and rates between the investigational and control subjects in the ITT Analysis Set. Overall, the investigational group reported a numerically greater rate of any AEs (79.7% - 141/177) as compared to the rate of any AEs recorded in the control subjects (71.4% - 137/192). However, the investigational group reported a numerically lower rate of SAEs (18.1% - 32/177) as compared to the rate of SAEs calculated for the control group (22.9% - 44/192). Table 9: Comparisons of Summary Adverse Event Percentages between Synergy Disc and ACDF Groups (ITT Analysis Set) | | Synergy Disc (N=177) | | | Control (N=192) | | | | --- | --- | --- | --- | --- | --- | --- | | Description | n | % | m | n | % | m | | Any Treatment-emergent Adverse Event | 141 | 79.7 | 408 | 137 | 71.4 | 271 | | Mild | 115 | 65 | 241 | 76 | 39.6 | 105 | | Moderate | 84 | 47.5 | 138 | 85 | 44.3 | 118 | | Severe | 28 | 15.8 | 28 | 43 | 22.4 | 48 | | Unknown | 1 | 0.6 | 1 | 0 | 0 | 0 | | Any Device Related Treatment-emergent Adverse Event1 | 32 | 18.1 | 36 | 66 | 34.4 | 83 | | Any Definitely Device Related Treatment-emergent Adverse Event | 3 | 1.7 | 3 | 1 | 0.5 | 1 | | Any Procedure Related Treatment-emergent Adverse Event1 | 72 | 40.7 | 90 | 75 | 39.1 | 104 | | Any Definitely Procedure Related Treatment-emergent Adverse Event | 39 | 22 | 44 | 28 | 14.6 | 34 | | Any Serious Treatment-emergent Adverse Event | 32 | 18.1 | 35 | 44 | 22.9 | 52 | | Mild | 2 | 1.1 | 2 | 0 | 0 | 0 | | Moderate | 8 | 4.5 | 8 | 7 | 3.6 | 8 | | Severe | 24 | 13.6 | 24 | 39 | 20.3 | 44 | | Unknown | 1 | 0.6 | 1 | 0 | 0 | 0 | | Any Device Related Serious Treatment-emergent Adverse Event1 | 5 | 2.8 | 6 | 21 | 10.9 | 21 | | Any Definitely Device Related Serious Treatment-emergent Adverse Event | 2 | 1.1 | 2 | 0 | 0 | 0 | | Any Procedure Related Serious Treatment-emergent Adverse Event1 | 6 | 3.4 | 7 | 23 | 12 | 24 | | Any Definitely Procedure Related Serious Treatment emergent Adverse Event | 5 | 2.8 | 6 | 8 | 4.2 | 8 | | N = Total number of subjects. n = Number of subjects in each category. The percentage calculation is based on the total number of subjects in the sections denoted by indent. m = Number of mentions in each category. 1 Includes 'Possibly Related', 'Probably Related' and 'Definitely Related'. | | | | | | | # All Adverse Events Table 10 lists all AEs reported as of the database lock by AE code, 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. As mentioned above, the P250028: FDA Summary of Safety and Effectiveness Data {27} investigational group presented with 408 events occurring in 79.7% (141/177) of subjects, compared to 271 events occurring in 71.4% (137/192) of the control subjects. The most commonly reported AEs included: Radiculopathy (investigational - 19.8%, 35/177; control - 15.6%, 30/192); Cervical Pain (investigational - 16.4%, 75/177; control - 15.1%, 29/192); and Trauma (investigational - 10.7%, 19/177; control - 6.8% 13/192). P250028: FDA Summary of Safety and Effectiveness Data 28 of 66 {28} Table 10: All Adverse Events (ITT Analysis Set) | System Organ Class Preferred Term | Synergy Disc (N=177) | | | Control (N=192) | | | | --- | --- | --- | --- | --- | --- | --- | | | n | % | m | n | % | m | | Any Adverse Event | 141 | 79.7 | 408 | 137 | 71.4 | 271 | | Musculoskeletal and Connective Tissue Disorders | 75 | 42.4 | 114 | 98 | 51 | 133 | | Cervical Pain | 29 | 16.4 | 32 | 29 | 15.1 | 33 | | Adjacent Segment Degeneration | 3 | 1.7 | 3 | 29 | 15.1 | 29 | | Lumbar Pain | 18 | 10.2 | 20 | 13 | 6.8 | 14 | | Musculoskeletal Inflammation | 17 | 9.6 | 19 | 12 | 6.3 | 16 | | Joint Pain | 12 | 6.8 | 13 | 3 | 1.6 | 3 | | Other Musculoskeletal Pain | 11 | 6.2 | 11 | 3 | 1.6 | 3 | | Soft Tissue Injury | 2 | 1.1 | 3 | 11 | 5.7 | 11 | | Pseudarthrosis | 0 | 0 | 0 | 7 | 3.6 | 7 | | Osteoarthritis | 3 | 1.7 | 3 | 3 | 1.6 | 3 | | Fracture, Any Bone | 2 | 1.1 | 2 | 3 | 1.6 | 3 | | Other Musculoskeletal and Connective Tissue Disorder | 2 | 1.1 | 2 | 3 | 1.6 | 3 | | Herniated Disc | 1 | 0.6 | 1 | 2 | 1 | 2 | | Spasms | 1 | 0.6 | 1 | 1 | 0.5 | 1 | | Spondylosistesis | 1 | 0.6 | 1 | 1 | 0.5 | 1 | | Sprain | 0 | 0 | 0 | 2 | 1 | 2 | | Cervical Degenerative Disc Disease | 0 | 0 | 0 | 1 | 0.5 | 1 | | Joint Instability | 0 | 0 | 0 | 1 | 0.5 | 1 | | Joint Stiffness | 1 | 0.6 | 1 | 0 | 0 | 0 | | Muscle Weakness | 1 | 0.6 | 1 | 0 | 0 | 0 | | Spinal Stenosis | 1 | 0.6 | 1 | 0 | 0 | 0 | | Nervous System Disorders | 60 | 33.9 | 88 | 47 | 24.5 | 58 | | Radiculopathy | 35 | 19.8 | 44 | 30 | 15.6 | 36 | | Compressive Neuropathy | 11 | 6.2 | 13 | 10 | 5.2 | 11 | | Numbness/Tingling | 12 | 6.8 | 13 | 3 | 1.6 | 3 | | Headache | 9 | 5.1 | 9 | 2 | 1 | 2 | | Other Nervous System Disorder | 3 | 1.7 | 3 | 0 | 0 | 0 | | Cerebrospinal fluid leak | 1 | 0.6 | 1 | 1 | 0.5 | 1 | | Dizziness | 2 | 1.1 | 2 | 0 | 0 | 0 | | Horner's Syndrome | 0 | 0 | 0 | 2 | 1 | 2 | | Ataxia | 1 | 0.6 | 1 | 0 | 0 | 0 | | Cognitive Disturbance | 1 | 0.6 | 1 | 0 | 0 | 0 | | Dysesthesia | 0 | 0 | 0 | 1 | 0.5 | 1 | | Myelopathy | 0 | 0 | 0 | 1 | 0.5 | 1 | | Neurological Deterioration (Motor, Sensory or Reflex) | 0 | 0 | 0 | 1 | 0.5 | 1 | | Tremors | 1 | 0.6 | 1 | 0 | 0 | 0 | | Other Complications/Events | 35 | 19.8 | 41 | 18 | 9.4 | 25 | | Trauma | 19 | 10.7 | 24 | 13 | 6.8 | 17 | | Cancer | 7 | 4 | 7 | 1 | 0.5 | 1 | | Other Event, Describe | 2 | 1.1 | 2 | 4 | 2.1 | 6 | | Adverse Reaction to Medication | 4 | 2.3 | 4 | 1 | 0.5 | 1 | | Surgery at a location other than the spine | 4 | 2.3 | 4 | 0 | 0 | 0 | | Gastrointestinal Disorders | 30 | 16.9 | 37 | 18 | 9.4 | 19 | | Dysphagia | 11 | 6.2 | 11 | 15 | 7.8 | 15 | | Constipation | 7 | 4 | 8 | 1 | 0.5 | 1 | | Other Gastrointestinal Disorder | 6 | 3.4 | 6 | 1 | 0.5 | 1 | | Gastrointestinal Pain | 3 | 1.7 | 3 | 0 | 0 | 0 | | Nausea | 2 | 1.1 | 2 | 1 | 0.5 | 1 | | Colitis | 2 | 1.1 | 2 | 0 | 0 | 0 | | Diarrhea | 1 | 0.6 | 1 | 1 | 0.5 | 1 | | Gastroesophageal Reflux Disease | 2 | 1.1 | 2 | 0 | 0 | 0 | | Pancreatitis | 1 | 0.6 | 1 | 0 | 0 | 0 | | Vomiting | 1 | 0.6 | 1 | 0 | 0 | 0 | P250028: FDA Summary of Safety and Effectiveness Data {29} | System Organ Class Preferred Term | Synergy Disc (N=177) | | | Control (N=192) | | | | --- | --- | --- | --- | --- | --- | --- | | | n | % | m | n | % | m | | Infections and Infestations | 29 | 16.4 | 35 | 10 | 5.2 | 11 | | Infection, Not at Surgical Site | 15 | 8.5 | 18 | 7 | 3.6 | 8 | | Infection, Surgical Site | 7 | 4 | 7 | 1 | 0.5 | 1 | | Rash | 4 | 2.3 | 4 | 2 | 1 | 2 | | Sinusitis | 5 | 2.8 | 5 | 0 | 0 | 0 | | Sepsis | 1 | 0.6 | 1 | 0 | 0 | 0 | | COVID-19 Infection | 15 | 8.5 | 16 | 0 | 0 | 0 | | COVID-19 | 15 | 8.5 | 16 | 0 | 0 | 0 | | Respiratory, Thoracic and Mediastinal Disorders | 12 | 6.8 | 13 | 2 | 1 | 2 | | Hoarseness | 4 | 2.3 | 4 | 1 | 0.5 | 1 | | Nasal Congestion | 3 | 1.7 | 3 | 0 | 0 | 0 | | Pneumonia | 2 | 1.1 | 2 | 1 | 0.5 | 1 | | Pulmonary Edema | 2 | 1.1 | 2 | 0 | 0 | 0 | | Airway Obstruction | 1 | 0.6 | 1 | 0 | 0 | 0 | | Sleep Apnea | 1 | 0.6 | 1 | 0 | 0 | 0 | | Cardiac Disorders | 10 | 5.6 | 12 | 3 | 1.6 | 3 | | Congestive Heart Failure | 3 | 1.7 | 4 | 1 | 0.5 | 1 | | Other Cardiac Disorders | 3 | 1.7 | 3 | 0 | 0 | 0 | | Atrial Fibrillation | 2 | 1.1 | 2 | 0 | 0 | 0 | | Syncope/Fainting | 1 | 0.6 | 1 | 1 | 0.5 | 1 | | Hyperlipidemia | 1 | 0.6 | 1 | 0 | 0 | 0 | | Mitral Valve Disease | 1 | 0.6 | 1 | 0 | 0 | 0 | | Ventricular Arrhythmia | 0 | 0 | 0 | 1 | 0.5 | 1 | | Immune System Disorders | 8 | 4.5 | 8 | 3 | 1.6 | 3 | | Allergic Reaction | 3 | 1.7 | 3 | 1 | 0.5 | 1 | | Inflammation | 2 | 1.1 | 2 | 2 | 1 | 2 | | Autoimmune Disorder | 3 | 1.7 | 3 | 0 | 0 | 0 | | Vascular Disorders | 7 | 4 | 8 | 3 | 1.6 | 3 | | Hypertension | 3 | 1.7 | 3 | 0 | 0 | 0 | | Other Vascular Disorder | 2 | 1.1 | 3 | 0 | 0 | 0 | | Thromboembolic Event | 2 | 1.1 | 2 | 0 | 0 | 0 | | Hypotension | 0 | 0 | 0 | 1 | 0.5 | 1 | | Lymphedema | 0 | 0 | 0 | 1 | 0.5 | 1 | | Phlebitis | 0 | 0 | 0 | 1 | 0.5 | 1 | | Psychiatric Disorders | 5 | 2.8 | 5 | 3 | 1.6 | 4 | | Depression | 4 | 2.3 | 4 | 2 | 1 | 2 | | Anxiety Disorders | 1 | 0.6 | 1 | 0 | 0 | 0 | | Delirium | 0 | 0 | 0 | 1 | 0.5 | 1 | | Insomnia | 0 | 0 | 0 | 1 | 0.5 | 1 | | Skin and Subcutaneous Tissue Disorders | 5 | 2.8 | 5 | 2 | 1 | 3 | | Other Skin and Subcutaneous Tissue Disorder | 1 | 0.6 | 1 | 1 | 0.5 | 2 | | Urticaria | 2 | 1.1 | 2 | 0 | 0 | 0 | | Itching/Pruritus | 1 | 0.6 | 1 | 0 | 0 | 0 | | Wound complications (e.g., dehiscence, bruising) and soft tissue damage | 1 | 0.6 | 1 | 0 | 0 | 0 | | Wound secretions / drainage | 0 | 0 | 0 | 1 | 0.5 | 1 | | Eye Disorders | 6 | 3.4 | 6 | 1 | 0.5 | 1 | | Blurred Vision | 2 | 1.1 | 2 | 0 | 0 | 0 | | Conjunctivitis | 2 | 1.1 | 2 | 0 | 0 | 0 | | Other Eye Disorders | 1 | 0.6 | 1 | 1 | 0.5 | 1 | | Glaucoma | 1 | 0.6 | 1 | 0 | 0 | 0 | P250028: FDA Summary of Safety and Effectiveness Data 30 of 66 {30} | System Organ Class Preferred Term | Synergy Disc (N=177) | | | Control (N=192) | | | | --- | --- | --- | --- | --- | --- | --- | | | n | % | m | n | % | m | | Ear and Labyrinth Disorders | 4 | 2.3 | 4 | 2 | 1 | 2 | | Vertigo | 1 | 0.6 | 1 | 2 | 1 | 2 | | Other Ear and Labyrinth Disorders | 2 | 1.1 | 2 | 0 | 0 | 0 | | Impaired Hearing | 1 | 0.6 | 1 | 0 | 0 | 0 | | Endocrine Disorders | 5 | 2.8 | 5 | 1 | 0.5 | 1 | | Other Endocrine Disorder | 2 | 1.1 | 2 | 1 | 0.5 | 1 | | Hypothyroidism | 2 | 1.1 | 2 | 0 | 0 | 0 | | Diabetes Mellitus | 1 | 0.6 | 1 | 0 | 0 | 0 | | General Disorders and Administrative Site Conditions | 4 | 2.3 | 4 | 2 | 1 | 2 | | Fatigue | 2 | 1.1 | 2 | 1 | 0.5 | 1 | | Flu-like symptoms | 2 | 1.1 | 2 | 0 | 0 | 0 | | Fever | 0 | 0 | 0 | 1 | 0.5 | 1 | | Renal and Urinary Disorders | 5 | 2.8 | 5 | 1 | 0.5 | 1 | | Urinary Retention | 2 | 1.1 | 2 | 1 | 0.5 | 1 | | Renal Calculi | 2 | 1.1 | 2 | 0 | 0 | 0 | | Other Renal and Urinary Disorder | 1 | 0.6 | 1 | 0 | 0 | 0 | | Blood and Lymphatic System Disorders | 1 | 0.6 | 1 | 0 | 0 | 0 | | Anemia | 1 | 0.6 | 1 | 0 | 0 | 0 | | Hepatobiliary Disorders | 1 | 0.6 | 1 | 0 | 0 | 0 | | Cholecystitis | 1 | 0.6 | 1 | 0 | 0 | 0 | | N = Total number of subjects. n = Number of subjects in each category. The percentage calculation is based on the total number of subjects in the sections denoted by indent. m = Number of mentions in each category. | | | | | | | ## All Adverse Events Time Course Table 11 presents all AEs through Month 24 for both treatment groups. Counts in this table represent the number of mentions, i.e., events. The time course interval where the highest number of AEs took place was between Month 12 and Month 24 for both the investigational and control groups. P250028: FDA Summary of Safety and Effectiveness Data {31} Table 11: Counts of Specific Adverse Events by Time of Occurrence – (ITT Analysis Population) (I = Synergy Disc, C = ACDF) | System Organ Class Preferred Term | <1 | | 1-3 | | 4-31 | | 32-91 | | 92-181 | | 182-366 | | 367-729 | | 730-790 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | I | C | I | C | I | C | I | C | I | C | I | C | I | C | I | C | | Any Adverse Event | 0 | 1 | 2 | 1 | 5 | 2 | 6 | 3 | 6 | 4 | 9 | 5 | 9 | 7 | 3 | 1 | | Musculoskeletal and Connective Tissue Disorders | 0 | 1 | 4 | 1 | 1 | 1 | 2 | 1 | 1 | 2 | 2 | 2 | 2 | 4 | 2 | 1 | | Cervical Pain | 0 | 0 | 1 | 1 | 3 | 6 | 6 | 4 | 2 | 7 | 1 | 6 | 9 | 8 | 1 | 1 | | Musculoskeletal Inflammation | 0 | 0 | 0 | 0 | 2 | 1 | 6 | 5 | 4 | 1 | 3 | 4 | 4 | 3 | 0 | 2 | | Lumbar Pain | 0 | 0 | 1 | 0 | 1 | 1 | 5 | 0 | 4 | 2 | 6 | 4 | 3 | 5 | 0 | 2 | | Adjacent Segment Degeneration | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 2 | 8 | 0 | 1 | 0 | 4 | | Joint Pain | 0 | 0 | 1 | 0 | 1 | 0 | 2 | 0 | 2 | 1 | 2 | 1 | 5 | 1 | 0 | 0 | | Other Musculoskeletal Pain | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 4 | 2 | 1 | 0 | 2 | 1 | 0 | 0 | | Soft Tissue Injury | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 3 | 0 | 2 | 2 | 1 | 0 | 2 | 0 | 1 | | Pseudarthrosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 4 | 0 | 2 | 0 | 0 | | Osteoarthritis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | | Fracture, Any Bone | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 2 | 1 | 0 | 0 | | Other Musculoskeletal and Connective Tissue Disorder | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | | Herniated Disc | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | | Spasms | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | | Spondylolisthesis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | | Sprain | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Cervical Degenerative Disc Disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Joint Instability | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | | Joint Stiffness | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Lumbar Degenerative Disc Disease | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Muscle Weakness | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Spinal Stenosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Nervous System Disorders | 0 | 0 | 6 | 4 | 1 | 4 | 1 | 9 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 3 | | Radiculopathy | 0 | 0 | 2 | 1 | 7 | 3 | 9 | 6 | 1 | 8 | 8 | 9 | 8 | 7 | 0 | 2 | | Compressive Neuropathy | 0 | 0 | 1 | 0 | 2 | 0 | 2 | 2 | 2 | 3 | 3 | 3 | 3 | 3 | 0 | 0 | | Numbness/Tingling | 0 | 0 | 1 | 0 | 3 | 1 | 3 | 0 | 2 | 1 | 4 | 0 | 0 | 1 | 0 | 0 | | Headache | 0 | 0 | 1 | 0 | 2 | 0 | 1 | 1 | 2 | 0 | 1 | 0 | 2 | 1 | 0 | 0 | | Other Nervous System Disorder | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Cerebrospinal fluid leak | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | | Dizziness | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Horner's Syndrome | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Ataxia | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Cognitive Disturbance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Dysesthesia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Myelopathy | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Neurological Deterioration (Motor, Sensory or Reflex) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Tremors | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Other Complications/Events | 0 | 0 | 0 | 1 | 3 | 2 | 4 | 3 | 8 | 4 | 1 | 7 | 1 | 8 | 0 | 0 | | Trauma | 0 | 0 | 0 | 0 | 2 | 2 | 3 | 2 | 5 | 4 | 8 | 4 | 6 | 5 | 0 | 0 | | Cancer | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 4 | 0 | 2 | 1 | 0 | 0 | | Other Event, Describe | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 3 | 0 | 2 | 0 | 0 | | Adverse Reaction to Medication | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Surgery at a location other than the spine | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0 | | Gastrointestinal Disorders | 0 | 0 | 7 | 5 | 1 | 1 | 4 | 4 | 4 | 1 | 5 | 1 | 7 | 5 | 0 | 2 | P250028: FDA Summary of Safety and Effectiveness Data 32 of 66 {32} | System Organ Class Preferred Term | <1 | | 1-3 | | 4-31 | | 32-91 | | 92-181 | | 182-366 | | 367-729 | | 730-790 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | I | C | I | C | I | C | I | C | I | C | I | C | I | C | I | C | | Dysphagia | 0 | 0 | 4 | 4 | 3 | 0 | 2 | 4 | 0 | 0 | 1 | 1 | 1 | 4 | 0 | 2 | | Constipation | 0 | 0 | 3 | 0 | 3 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Other Gastrointestinal Disorder | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 3 | 0 | 0 | 0 | | Gastrointestinal Pain | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | | Nausea | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Colitis | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Diarrhea | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Gastroesophageal Reflux Disease | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Pancreatitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Vomiting | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Infections and Infestations | 0 | 0 | 2 | 2 | 7 | 5 | 9 | 0 | 5 | 0 | 3 | 1 | 9 | 2 | 0 | 1 | | Infection, Not at Surgical Site | 0 | 0 | 0 | 1 | 1 | 3 | 4 | 0 | 5 | 0 | 1 | 1 | 7 | 2 | 0 | 1 | | Infection, Surgical Site | 0 | 0 | 0 | 0 | 5 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Rash | 0 | 0 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Sinusitis | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | | Sepsis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | COVID-19 Infection | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 4 | 0 | 4 | 0 | 4 | 0 | 0 | 0 | | COVID-19 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 4 | 0 | 4 | 0 | 4 | 0 | 0 | 0 | | Respiratory, Thoracic and Mediastinal Disorders | 0 | 0 | 3 | 1 | 2 | 0 | 1 | 0 | 3 | 0 | 2 | 0 | 1 | 1 | 1 | 0 | | Hoarseness | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Nasal Congestion | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Pneumonia | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | | Pulmonary Edema | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Airway Obstruction | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Sleep Apnea | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Cardiac Disorders | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 4 | 1 | 5 | 1 | 0 | 0 | | Congestive Heart Failure | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 3 | 0 | 0 | 0 | | Other Cardiac Disorders | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | | Atrial Fibrillation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Syncope/Fainting | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Hyperlipidemia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Mitral Valve Disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Ventricular Arrhythmia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Immune System Disorders | 0 | 0 | 3 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | | Allergic Reaction | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Inflammation | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | | Autoimmune Disorder | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | | Vascular Disorders | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 0 | 2 | 1 | 3 | 0 | 0 | 1 | 0 | 0 | | Hypertension | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | | Other Vascular Disorder | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Thromboembolic Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Hypotension | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Lymphedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Phlebitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | | Psychiatric Disorders | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 2 | 2 | 1 | 0 | 0 | | Depression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 2 | 2 | 0 | 0 | 0 | | Anxiety Disorders | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Delirium | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Insomnia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Skin and Subcutaneous Tissue Disorders | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 3 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | P250028: FDA Summary of Safety and Effectiveness Data 33 of 66 {33} | System Organ Class Preferred Term | <1 | | 1-3 | | 4-31 | | 32-91 | | 92-181 | | 182-366 | | 367-729 | | 730-790 | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | I | C | I | C | I | C | I | C | I | C | I | C | I | C | I | C | | Other Skin and Subcutaneous Tissue Disorder | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Urticaria | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Itching/Pruritus | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Wound complications (e.g., dehiscence, bruising) and soft tissue damage | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Wound secretions / drainage | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Eye Disorders | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 2 | 1 | 0 | 0 | | Blurred Vision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | | Conjunctivitis | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Other Eye Disorders | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | | Glaucoma | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Ear and Labyrinth Disorders | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 2 | 0 | 0 | 0 | | Vertigo | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | | Other Ear and Labyrinth Disorders | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | | Impaired Hearing | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | Endocrine Disorders | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 2 | 0 | 0 | 0 | | Other Endocrine Disorder | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | | Hypothyroidism | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | | Diabetes Mellitus | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | | General Disorders and Administrative Site Conditions | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | | Fatigue | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Flu-like symptoms | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |…
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