CARTIVA SYNTHETIC CARTILAGE IMPLANT

P150017 · Cartiva, Inc. · PNW · Jul 1, 2016 · Orthopedic

Device Facts

• Record ID: P150017
• Device Name: CARTIVA SYNTHETIC CARTILAGE IMPLANT
• Applicant: Cartiva, Inc.
• Product Code: PNW · Orthopedic
• Decision Date: Jul 1, 2016
• Decision: APPR
• Device Class: Class 3
• Attributes: Therapeutic

Indications for Use

The Cartiva Synthetic Cartilage Implant is intended for use in the treatment of patients with painful degenerative or post-traumatic arthritis (hallux limitus or hallux rigidus) in the first metatarsophalangeal joint with or without the presence of mild hallux valgus

Device Story

Cartiva SCI is a molded, cylindrical, viscoelastic hydrogel implant composed of polyvinyl alcohol and saline. It is designed to replace focal areas of damaged cartilage in the first metatarsophalangeal (MTP) joint. The device is implanted via a minimally invasive, press-fit procedure performed by orthopedic surgeons. It functions as a bearing surface to reduce pain and maintain joint range of motion, serving as an alternative to arthrodesis (joint fusion). The device does not regrow or replace native cartilage. Healthcare providers assess patient outcomes post-operatively through pain (VAS) and function (FAAM) scores. By preserving joint motion, the device aims to provide a faster recovery and maintain the option for future surgical interventions compared to fusion.

Clinical Evidence

Pivotal prospective, randomized, controlled, multi-center MOTION study (n=202). Compared Cartiva SCI to arthrodesis. Primary endpoint: composite of VAS pain reduction (≥30%), FAAM ADL function maintenance, freedom from major complications/SSSI, and radiographic success at 24 months. Results: 79.8% Cartiva success vs 78.7% arthrodesis (mITT completers). Non-inferiority met (LB 95% CI -10.29%). Secondary endpoints showed arthrodesis had greater pain reduction, while Cartiva maintained joint motion.

Technological Characteristics

Molded cylindrical hydrogel implant composed of polyvinyl alcohol and saline. Two sizes: 8 mm and 10 mm diameter/depth. Press-fit implantation. Instrumentation includes stainless steel Placer, Introducer, and Metatarsal Drill Bit. Sterilized via E-beam radiation (ISO 11137-2). Shelf life 24 months.

Indications for Use

Indicated for patients ≥18 years with painful degenerative or post-traumatic arthritis (hallux limitus or hallux rigidus) of the first metatarsophalangeal joint, with or without mild hallux valgus (≤20°). Contraindicated in patients with active foot infection, polyvinyl alcohol allergy, inadequate bone stock (avascular necrosis, large osteochondral cysts >1 cm), lesions >10 mm, gout with tophi, or conditions eliminating implant support (e.g., cancer, osteoporosis, systemic metabolic bone disorders).

Regulatory Classification

Identification

The device is a metatarsophalangeal joint cartilage replacement device that is implanted in the metatarsal head of the first metatarsophalangeal joint.

Submission Summary (Full Text)

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# SUMMARY OF SAFETY AND EFFECTIVENESS DATA

## I. GENERAL INFORMATION

Device Generic Name: Synthetic Cartilage Implant

Device Trade Name: Cartiva® Synthetic Cartilage Implant (SCI)

Device Product Code: PNW

Applicant’s Name/Address: Cartiva, Incorporated
6120 Windward Parkway, Suite 220
Alpharetta, GA 30005

Date of Panel Recommendation: April 20, 2016

Premarket Approval Application: P150017
(PMA Number)

Date of Notice of Approval to the Applicant: July 1, 2016

## II. INDICATIONS FOR USE

The Cartiva Synthetic Cartilage Implant is intended for use in the treatment of patients with painful degenerative or post-traumatic arthritis (hallux limitus or hallux rigidus) in the first metatarsophalangeal joint with or without the presence of mild hallux valgus¹

## III. CONTRAINDICATIONS

The Cartiva SCI device should not be implanted in subjects with the following conditions:

- Active infection of the foot
- Known allergy to polyvinyl alcohol
- Inadequate bone stock due to significant bone loss, avascular necrosis, and/or large osteochondral cyst (> 1 cm) of the first metatarsophalangeal joint
- Lesions of the first metatarsal head greater than 10 mm in size
- Diagnosis of gout with tophi
- Physical conditions that would tend to eliminate adequate implant support (e.g., insufficient quality or quantity of bone resulting from cancer, congenital dislocation, or osteoporosis), systemic and metabolic disorders leading to progressive deterioration of

¹ A hallux valgus angle less than or equal to 20° (greater than 20° was an exclusion criteria in the clinical study).

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bone (e.g., cortisone therapies or immunosuppressive therapies), and/or tumors of the supporting bone structures

## IV. PRECAUTIONS

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

- Pediatric patients (< 22 years of age)
- Subjects with osteonecrosis of the first metatarsal

Osteoarthritis involving the first metatarsophalangeal joint with grade 0 or 1 hallux rigidus per the Coughlin Scale²

The safety and effectiveness of the Cartiva SCI device for treatment in the presence of hallux varus to any degree or hallux valgus >20° is unknown.

The safety and effectiveness of using more than one Cartiva SCI device per joint is unknown.

The safety and effectiveness of the Cartiva SCI device at anatomic locations other than the first metatarsophalangeal joint is unknown.

The Cartiva SCI device should only be used by experienced surgeons who have undergone training in the use of this device. A lack of adequate experience and/or training may lead to a higher incidence of adverse events.

Examine all instruments prior to surgery for wear or damage. Replace any worn or damaged instruments.

Use aseptic technique when removing the Cartiva SCI device from the innermost packaging.

Carefully inspect the device and its packaging for any signs of damage, including damage to the sterile barrier. Do not use Cartiva SCI devices if the packaging is damaged or the implant shows signs of damage.

Use care when handling the Cartiva device to ensure that it does not come in contact with objects that could damage the implant. Damaged implants are no longer functionally reliable.

The Cartiva SCI device should not be used with components or instruments from other manufacturers.

² Coughlin MJ, Shurnas PS. Hallux rigidus. Grading and long-term results of operative treatment. American Journal of Bone Joint Surgery. 85-A(11):2072-88. November 2003

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Cartiva SCI device should not be re-used or re-implanted. Ensure proper alignment and placement of device components as misalignment may cause excessive wear and/or early failure of the device.

# V. DEVICE DESCRIPTION

The Cartiva SCI device is a polymer-based biomaterial implant for treatment of first metatarsophalangeal joint osteoarthritis. The viscoelastic hydrogel implant's material properties are conducive to replacing focal areas of damaged cartilage, providing pain reduction, and maintaining range of motion. The Cartiva SCI device does not regrow or replace cartilage. The device is intended as an alternative to fusion procedures, hereafter referred to as arthrodesis.

The device is a molded cylindrical implant composed of polyvinyl alcohol and saline that is placed into the metatarsal head in the first metatarsophalangeal (MTP) joint via press-fit implantation. This biocompatible material is widely used in other FDA cleared and approved medical devices, such as contact lenses, permanently implanted injectable embolic spheres, and nerve cuffs. The Cartiva SCI device is implanted during a short and minimally invasive implantation procedure that allows for faster recovery, preservation of joint function compared to the surgical fusion of the MTP joint, and preserves the option for future surgical treatment in the event of complications.

Figure 1: Cartiva Synthetic Cartilage Implant

The Cartiva SCI device is manufactured in two sizes for treatment of first metatarsophalangeal joint osteoarthritis:

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| Catalog Number | Size |
| --- | --- |
| CAR-08 | 8 mm
(8 mm diameter x 8 mm depth) |
| CAR-10 | 10 mm
(10 mm diameter x 10 mm depth |

The Cartiva SCI device is placed into the first MTP using dedicated instrumentation in a straightforward and bone-preserving surgical procedure. The Cartiva SCI instrumentation includes the Placer, Introducer, Metatarsal Drill Bit, guide pins (off the shelf), and sterilization tray. Each piece of instrumentation is made of surgical grade stainless steel and is provided to the user non-sterile. All instrumentation, with the exception of the guide pins are reusable and are provided with cleaning and sterilization instructions. The guide pins are provided with sterilization instructions and are disposed of after a single use.

## VI. ALTERNATIVE PRACTICES AND PROCEDURES

Alternative treatment options for first metatarsophalangeal osteoarthritis depend upon the severity of a patient’s symptoms and may include non-operative and operative treatments.

- Non-operative treatment options include the use of orthotics or accommodative footwear, use of a stiff-soled shoe, use of pain relievers and anti-inflammatory medicines, injections, hot/cold temperature baths, and limitation of activities.
- Surgical treatment options for metatarsophalangeal osteoarthritis include: cheilectomy, a joint salvage procedure that involves resection of the dorsal osteophytes from both the metatarsal and proximal phalanx and removal of the degenerative portion of the metatarsal head; hemiarthroplasty, a joint sparing procedure that involves the implantation of a device to resurface the first metatarsophalangeal head; total joint replacement, a procedure which involves replacing the entire metatarsophalangeal joint with an implant; or, arthrodesis, a procedure in which the two sides of the metatarsophalangeal joint are debrided of cartilage, and the bones are held together with plates and/or screws so that the bones grow together.

Each alternative has advantages and disadvantages. Patients should discuss the available alternatives with their physician and select the option that best meets their clinical condition, lifestyle and expectations.

## VII. MARKETING HISTORY

The Cartiva SCI device has been commercially distributed since 2002 with approvals in Europe, Canada and Brazil. Through the international market, the Cartiva SCI device has been used in over 4,000 procedures in various joint including the first metatarsophalangeal joint. The Cartiva SCI device has not been withdrawn from marketing for any reason.

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# VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the potential adverse effects (e.g., complications). In addition to the risks listed below, there is also the risk that surgery may not be effective in relieving symptoms, or may cause worsening of symptoms. Additional surgery may be required to correct some of the adverse effects.

1. Risks associated with surgical procedures involving the foot include: infection, blood clots, blood loss, damage to adjacent nerves, arteries, or veins, anesthesia-related problems, allergic reaction, numbness in the toes, painful scars, pain when wearing shoes or walking, incomplete correction, recurrence of the deformity, heart attack, stroke, nerve damage, deep vein thrombosis (DVT), pulmonary embolus (PE), and death.

2. Risks associated with implantation of the Cartiva Synthetic Cartilage Implant include infection, inflammation, pain, swelling, effusion, joint irritation, fibrosis, joint instability, joint malalignment, periarticular cyst, bone cyst, bone loss, sesamoid bone(s) irritation, sesamoid bone(s) fracture, metatarsal bone fracture, osteonecrosis, avascular necrosis, implant fracture, implant loosening, implant dislocation, implant dislodgement, implant subsidence, revision or conversion to arthrodesis, allergic reaction to polyvinyl alcohol (PVA), progressive osteoarthritis (OA), incorrect implant placement, and damage to adjacent or surrounding tissues.

For the specific adverse events that occurred in the MOTION clinical study, please see Section X.

# IX. SUMMARY OF PRE-CLINICAL STUDIES

A variety of mechanical and other non-clinical tests were conducted to characterize the mechanical properties and performance of the Cartiva SCI device, as outlined below. This testing included biocompatibility testing, long-term implant compatibility testing, wear testing, and testing to evaluate that the device provides a sufficient loading surface for the first MTP joint. Testing met all predefined requirements.

# A. BIOCOMPATIBILITY

The Cartiva SCI device and instrumentation are designed to be biocompatible for their respective intended use and duration of contact with the body. As summarized in Table 1 below, the Cartiva SCI device was assessed for biocompatibility per the testing guidelines outlined in ISO 10993.

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Table 1: Biocompatibility Testing of the Cartiva SCI Device

| Study | Test Method | Results |
| --- | --- | --- |
| Cytotoxicity | L929 MEM Elution | Non-cytotoxic |
| Cytotoxicity | Direct Contact | Non-cytotoxic |
| Sensitization | Kligman Maximization | Non-sensitizer |
| Irritation/Intracutaneous | IC Injection | Negligible irritant |
| Acute Systemic Toxicity | Systemic Injection | Negative |
| Subchronic Toxicity | Femoral Condyle Implantation | Non-toxic |
| Chronic Toxicity | Femoral Condyle Implantation | Non-toxic |
| Genotoxicity | Ames Reverse Mutation | Non-mutagenic |
| Genotoxicity | Chromosomal Aberration Assay | Non-clastogenic |
| Genotoxicity | Rodent Bone Marrow Micronucleus | Non-clastogenic |
| Implantation | Bone Implantation in Femoral Condyle | Negative/no reaction |
| Pyrogenicity | Rabbit Pyrogen Test | Non-pyrogenic |

The Cartiva SCI device is placed into its implant position using dedicated instrumentation. As summarized in Table 2 below, the Cartiva SCI instruments were assessed for biocompatibility per the testing guidelines outlined in ISO 10993.

Table 2: Biocompatibility Testing of the Cartiva SCI Instrumentation

| Study | Test Method | Results |
| --- | --- | --- |
| Cytotoxicity | L929 MEM Elution | Non-cytotoxic |
| Sensitization | Kligman Maximization | Non-sensitizer |
| Irritation/Intracutaneous | IC Injection | Negligible irritant |

# B. MECHANICAL CHARACTERIZATION TESTING

A summary of the mechanical characterization testing of the Cartiva SCI device is presented below in Table 3.

Table 3: Mechanical Characterization Testing of the Cartiva SCI Device

| Test | Purpose | Results |
| --- | --- | --- |
| Confined Compression (aggregate modulus) | To characterize the aggregate moduli or stiffness at equilibrium. | The mean aggregate modulus for the Cartiva SCI device was 6.7 ±1.0 MPa. This value supported selection of wear test parameters. |

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| Test | Purpose | Results |
| --- | --- | --- |
| Unconfined Compression (Young's modulus) | To characterize the deformation resistance of the device to an applied load and determine the compatibility with surrounding native tissues. | The compressive moduli and equilibrium elastic moduli observed for the Cartiva SCI device was (0.31 to 0.80 unconfined compression moduli3; equilibrium elastic moduli mean .677 ± .223 MPa4), which is less than traditional hard joint replacement materials. |
| Shear | To obtain a baseline characterization of the simple shear properties as the device functions as a cartilage replacement material. | Fatigued devices exhibited no change in shear properties and resistance to mechanically induced degradation properties. All devices exhibited full 100% lateral shear strain without tearing or showing shear fracture. |
| Creep | To characterize the creep and creep recovery responses of the device under clinical loading conditions. | The compressive creep observed was due to water loss with compressive loading, which resulted in an average mass loss of 21% across all samples. Under clinical loading, the device still had sufficient mass to serve as a bearing surface for the joint. All samples demonstrated significant recovery swelling upon the removal of the compressive load, as anticipated for a porelastic hydrogel material and thus is expected to tolerate clinical loading and unloading of the joint. |
| Dynamic Axial Compression (S-N Analysis) | To determine the fatigue endurance limit of the device (the maximum axial compression stress amplitude that will not cause fatigue failure in 5,000,000 cycles). | This study demonstrates that catastrophic failure of the Cartiva SCI device does not occur even when the device is subjected to stresses approximately 6 times greater than the 4 MPa anticipated peak load for the first MTP. |
| Particulate Implant Testing | To assess the bioreactivity of device-generated wear debris. | Wear debris representing 5 years of expected debris was implanted in a rabbit model. There were no complications on injection. No test article-related adverse changes occurred. No significant findings on clinical observation, gross pathology, histomorphometry, or histopathology of localized tissue. Systemic tissues showed no microscopic changes related to the treatment. Overall, no local or systemic response was evident. |

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C. PERFORMANCE TESTING

Performance testing was conducted to evaluate the device in simulated clinical use conditions or under simulated worst-case conditions. These are described below:

Fatigue Testing

The purpose of dynamic fatigue testing of the Cartiva SCI device was to assess if the device has adequate compressive strength to survive the repetitive, compressive loads that occur clinically in the first metatarsophalangeal joint. Mechanical fatigue was carried out utilizing the anticipated clinical loading. Cartiva SCI devices withstood the equivalent of 5 years of continual cyclic loading without fracturing, indicating a mechanical durability representing 5 years of continuous use.

Wear Testing

Cartiva SCI devices were subjected to loading parameters reflecting the normal gait cycle and opposing surfaces that were intended to simulate the wear environment of the first metatarsophalangeal joint. The Cartiva SCI devices sustained only minor damage during the 5,000,000 cycles under worst-case wear conditions under maximum loading that simulated 5 years of continuous walking.

To assess the long-term effect of the material and possible wear debris, a worst-case 5-year amount of Cartiva SCI device particulate was injected intra-articularly into the rabbit knee in amounts 9 times greater than that identified during wear testing. The test conditions applied incorporated the use of excessive quantities of potential wear debris in a bolus application. The rabbit particulate implant study demonstrated a lack of local or systemic toxicity to the Cartiva SCI device particulate at both 3-months and 6-months. The particulate implant testing results demonstrated no toxic or adverse reactions to the wear debris from the hydrogel material.

The average total mass of debris collected per specimen over the 5 million cycles was 1.64 mg (0.18% of average initial mass of the test articles) based on the worst-case assumption that all of the debris was of Cartiva device origin. The morphology of the particulate recovered was generally granular, oval in shape and with average aspect ratios < 1.8. The associated volumetric wear rate was determined to be 0.53 mm³/yr. The amount of wear produced under these testing parameters indicates a low rate of wear compared with other polymers utilized in bearing surfaces of orthopedic implants. However, the threshold wear rate to induce osteolysis in the vicinity of the first metatarsophalangeal joint is unknown.

One-Year Animal Implant Study

A one-year animal implant study was conducted in accordance with Good Laboratory Practices (GLP) in a load-bearing large animal model (goat). The intent of the study was to evaluate the integrity of the implanted device after 1 year and to assess local and systemic toxicity of the Cartiva SCI device, as well as to, determine whether the implants elicit any inflammatory

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reaction in a load-bearing environment. The test animals received Cartiva SCI devices while the controls received empty defects. Both groups were followed out to one year with an interim assessment at six months. The surgical procedure was well tolerated by all animals. There were no obvious differences observed between the two groups following necropsy. There were no instances of device failure, such as dislodgement or fragmentation. There were non-significant changes to the opposing tibial surface in both groups. No differences in presence of subarticular cysts between test animals that received Cartiva SCI device, as compared to the control, were observed. No implant wear and no particulate migration were observed. The results of the study demonstrated that there was no local or systemic toxicity, no ongoing chronic inflammatory reaction around the implant, and no osteolytic bone loss.

## Conclusion

These data fully characterize the mechanical properties and performance of the device in simulated clinical use conditions or under simulated worst-case conditions.

## D. STERILIZATION AND CLEANING

The Cartiva SCI device is provided sterile within a tray-in-pouch configuration that allows for aseptic introduction into the sterile field. The primary packaging (the tray) holds the Cartiva SCI device and saline and is sealed with a foil lid. The sealed tray is packaged in a secondary outer Tyvek pouch. The Cartiva SCI device is implanted using dedicated instrumentation. All instruments outside of the guide pins are reusable. All instrumentation, including guide pins and the sterilization tray are provided with cleaning and sterilization instructions. The guide pins are disposed of after a single use.

The final, packaged Cartiva SCI device is terminally sterilized to a sterility assurance level of $10^{-6}$ using E-beam radiation per a validated method in accordance with industry standard ISO 11137-2 Third Edition 2013, Sterilization of Health Care Products – Radiation – Part 2: Establishing the Sterilization Dose – Sterility.

The Cartiva SCI instrumentation's cleaning and sterilization cycle specifications are validated and consistent with cycle specifications outlined in AAMI TIR 12:2010 Designing, testing and labeling reusable medical devices for reprocessing in health care facilities: A guide for medical device manufacturers; AAMI TIR 30:2011 A Compendium of Processes, Materials, Test Methods, and Acceptance Criteria for Cleaning Reusable Medical Devices, and ANSI/AAMI ST79 Comprehensive Guide to Steam Sterilization and Sterility Assurance in Health Care Facilities, including a Pre-Vacuum $132^{\circ}\mathrm{C}$ 4-minute cycle and a Gravity $132^{\circ}$ 25-minute cycle.

## E. PACKAGING AND SHELF LIFE

The Cartiva SCI device is provided in sterile packaging and ready for use. The Cartiva SCI device packaging, a tray-in-pouch configuration, has been qualified to maintain device functionality and sterility and tested in accordance with ASTM F1929-98 Standard Test Method

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for Detecting Seal Leaks in Porous Medical Packaging by Dye Penetration and ASTM D4169 Standard Practice for Performance Testing of Shipping and Containers and Systems.

The Cartiva SCI instrumentation is provided non-sterile. The Cartiva SCI instrumentation packaging has been qualified to maintain device functionality through simulated distribution conditions in accordance with ASTM D4169 Standard Practice for Performance Testing of Shipping and Containers and Systems.

The Cartiva SCI device has a labeled shelf life of 24 months. This duration was qualified by direct testing of real-time aged product to confirm retention of critical physical and mechanical characteristics of the device and to ensure the tray-in-pouch packaging retained integrity of both the outer and inner packaging seals.

The Cartiva SCI instrumentation is provided non-sterile, is reusable, and does not carry a labeled shelf life.

## X. SUMMARY OF CLINICAL STUDIES

This PMA presents data from a prospective, randomized, controlled multi-center clinical trial performed to evaluate the safety and effectiveness of the Cartiva SCI device compared to arthrodesis for the treatment of subjects with painful degenerative or post-traumatic arthritis (hallux limitus or hallux rigidus) involving the first metatarsophalangeal joint, with or without the presence of mild hallux valgus. A summary of the clinical trial is presented below.

## A. STUDY DESIGN

The pivotal clinical study (the "MOTION" Study) compared the Cartiva SCI device to the control treatment, arthrodesis. The study was a prospective, randomized (2:1), multi-center, two arm, unmasked, concurrently controlled, non-inferiority clinical study in 202 subjects treated at 12 sites in the United Kingdom and Canada. The study was conducted in compliance with ICH guidelines and Good Clinical Practice (GCP) guidelines. All sites had Ethics Approval and subjects were required to sign an Informed Consent in compliance with 21 CFR Part 50 and ICH guidelines. Subjects were treated between October 2009 and February 2013. The database for this PMA reflected data collected through February 2015 and was updated with a retrospective analysis of peri-operative data in October 2015.

The study employed a composite primary endpoint that reflected three outcomes (pain, function, and safety). The individual components of the primary outcome measures were a Visual Analog Scale (VAS) to assess pain, the Foot and Ankle Ability Measure (FAAM) to assess function, and the absence of major complications and subsequent surgical interventions to assess safety.

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This was a frequentist, non-inferiority study with a pre-specified endpoint of the proportion of subjects achieving success (i.e., meeting all criteria of the primary composite endpoint) and a non-inferiority margin of 15%. The statistical model for this endpoint was two independent binomial proportions.

Letting $p_{\text{Cartiva}}$ and $p_{\text{Fusion}}$ represent the proportions with 24-month success for the Cartiva SCI device and arthrodesis groups, respectively, and $\delta = 0.15$ being the non-inferiority margin, the statistical hypotheses for the pre-specified primary endpoint were:

$$
\begin{array}{l}
\mathrm{H}_0: \mathrm{p}_{\text{Cartiva}} - \mathrm{p}_{\text{Fusion}} \leq -\delta \\
\mathrm{H}_a: \mathrm{p}_{\text{Cartiva}} - \mathrm{p}_{\text{Fusion}} > -\delta \\
\end{array}
$$

These statistical hypotheses were assessed via one-sided 95% confidence intervals on the difference in the proportion of responders in the Cartiva group minus the proportion of responders in the arthrodesis group, see Table 27 for details regarding the definition of a "responder".

In addition to the outcomes comprising the primary composite endpoint, other functional and quality-of-life outcomes scores were studied, and included active MTP dorsiflexion, Revised Foot Function Index (FFI-R), and SF-36 Physical Function Scores. Fisher's Exact test was used to calculate all p-values.

The initial two subjects enrolled and treated at each site were not randomized to ensure surgeons were adequately familiar with the procedure.

Upon confirmation of eligibility, subjects were randomized into one of two treatment groups: (1) Cartiva SCI device into the MTP joint, or (2) arthrodesis, a procedure in which the two sides of the MTP joint are held together with plates and/or screws so that the bones grow together and no longer move.

The investigators, who were fellowship-trained and board-certified orthopedic foot and ankle surgeons, performed clinical and radiographic assessments in accordance with the protocol to monitor subject outcomes. A radiographic assessment was performed by an independent core lab with an independent radiologist who assessed subjects in both treatment arms according to a pre-specified protocol.

## Clinical Inclusion/Exclusion Criteria

To be eligible for the MOTION study, subjects were required to be eligible for an arthrodesis procedure and meet all of the inclusion criteria and none of the exclusion criteria, which are presented below in Table 4.

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Table 4: MOTION Study Inclusion/Exclusion Criteria

| Study Inclusion Criteria | Study Exclusion Criteria |
| --- | --- |
| • ≥18 years of age;
• Degenerative or post-traumatic arthritis of the first metatarsophalangeal joint and is a candidate for arthrodesis with Grade 2, 3, or 4²;
• Pre-operative VAS Pain score of ≥40;
• Presence of good bone stock, with <1cm osteochondral cyst and without need for bone graft;
• Capable of completing self-administered questionnaires;
• Be willing and able to return for all study-related follow-up procedures;
• Have not participated in any other research protocol within the last 30 days, and will not participate in any other research protocol during this study;
• If female, is either using contraception or is postmenopausal, or male partner is using contraception; and
• Have been informed of the nature of the study, agreeing to its requirements, and have signed the informed consent approved by the IRB/Ethics Committee. | • <18 years of age;
• Degenerative or post-traumatic arthritis of the first metatarsophalangeal joint and is not a candidate for arthrodesis with Grade 0 or 1²;
• Pre-operative VAS Pain score <40;
• Active bacterial infection of the foot;
• Additional ipsilateral lower limb (hip, knee, ankle, or foot) pathology that requires active treatment (i.e., surgery, brace);
• Bilateral degenerative or post-traumatic arthritis of the first metatarsophalangeal joints that would require simultaneous treatment of both MTP joints;
• Previous cheilectomy resulting in inadequate bone stock;
• Inflammatory arthropathy;
• Diagnosis of gout;
• Any significant bone loss, avascular necrosis, and/or large osteochondral cyst (>1cm) of the first metatarsophalangeal joint;
• Lesions greater than 10 mm in size;
• Hallux varus to any degree or hallux valgus >20°;
• Physical conditions that would tend to eliminate adequate implant support (e.g., insufficient quality or quantity of bone resulting from cancer, congenital dislocation, or osteoporosis), systemic and metabolic disorders leading to progressive deterioration of bone (e.g., cortisone therapies or immunosuppressive therapies), and/or tumors and/or cysts >1cm of the supporting bone structures;
• Patient is on chronic anticoagulation due to a bleeding disorder or has taken anticoagulants within 10 days prior to surgery;
• Patient was diagnosed with cancer in the last two (2) years and received treatment with chemotherapy or received radiation to the lower extremity to be treated with Cartiva SCI device or arthrodesis;
• Suspected allergic reaction to polyvinyl alcohol;
• Muscular imbalance, peripheral vascular disease that prohibits adequate healing, or a poor soft-tissue envelope in the surgical field, absence of musculoligamentous supporting structures, or |

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| Study Inclusion Criteria | Study Exclusion Criteria |
| --- | --- |
| | peripheral neuropathy;
• In the opinion of the Investigator, any medical condition that makes the subject unsuitable for inclusion in the study, including, but not limited to subjects with a diagnosis of concomitant injury that may interfere with healing; subjects with clinically significant renal, hepatic, cardiac, endocrine, hematologic, autoimmune or any systemic disease or systemic infection which may make interpretation of the results difficult; subjects who have undergone systemic administration within 30 days prior to implantation of any type of corticosteroid, antineoplastic, immunostimulating or immunosuppressive agents;
• Co-morbidity that reduces life expectancy to less than 36 months;
• If female, be pregnant, planning to become pregnant during the course of the study, breast-feeding, or if childbearing age, is not using contraception;
• History of substance abuse (e.g. recreational drugs, narcotics, or alcohol);
• Is a prisoner or ward of the state;
• Are unable to meet the treatment and follow-up protocol requirements; or
• Are being compensated under workers’ compensation or are currently involved in litigation. |

## Follow-up Schedule

All subjects were evaluated pre-operatively, intra-operatively, post-operatively prior to discharge, and post-operatively at 2 weeks, 6 weeks, and at 3, 6, 12, and 24 months. This included the evaluation of pain as measured by the Visual Analog Scale (VAS), function as assessed by the Foot and Ankle Ability Measure (FAAM) Score, and the assessment of major complications and subsequent secondary surgical interventions. In addition, range of motion and radiographic outcomes were assessed, and subject and investigator questionnaires were completed. Subjects were required to have discontinued all pain medications (NSAIDs, narcotics, and any other analgesics) for a minimum of 8 hours prior to competing any of the study assessments. All complications and adverse events, device-related or not, were evaluated over the course of the study. The schedule for the various assessments is shown below in Table 5:

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Table 5: MOTION Study Assessments

| | Baseline | Operative/Discharge (Day 0) | 2w | 6w | 3m | 6m | 12m | 18m | 24m | Unscheduled |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Window Days | | | ±7 | ±14 | ±14 | ±14 | ±60 | ±14 | ±60 | |
| Eligibility/Informed Consent | ✓ | | | | | | | | | |
| Medical History | ✓ | | | | | | | | | |
| Foot Exam | ✓ | | ✓ | ✓ | ✓ | ✓ | ✓ | | ✓ | ✓ |
| Foot X-ray | ✓ | | ✓ | ✓ | ✓ | ✓ | ✓ | | ✓ | ✓ |
| General Health | ✓ | | ✓ | ✓ | ✓ | ✓ | ✓ | | ✓ | ✓ |
| VAS Pain | ✓ | | ✓ | ✓ | ✓ | ✓ | ✓ | | ✓ | ✓ |
| Foot Function Index Revised (FFI-R) | ✓ | | ✓ | ✓ | ✓ | ✓ | ✓ | | ✓ | ✓ |
| Foot & Ankle Ability Measure (FAAM) | ✓ | | ✓ | ✓ | ✓ | ✓ | ✓ | | ✓ | ✓ |
| SF-36 Health Survey | ✓ | | | ✓ | ✓ | ✓ | ✓ | | ✓ | ✓ |
| Global Assessment (Subject & Site PI) | | | ✓ | ✓ | ✓ | ✓ | ✓ | | ✓ | ✓ |
| Operative/Discharge Form | | ✓ | | | | | | | | |
| Follow-up Visit Form | | | ✓ | ✓ | ✓ | ✓ | ✓ | | ✓ | ✓ |
| Telephone Follow-up | | | | | | | | ✓ | | |
| AE Reporting | | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |

## Clinical Endpoints

The effectiveness of the Cartiva SCI device was assessed and compared to treatment with arthrodesis using a composite clinical endpoint. Success required freedom from subsequent secondary surgical interventions (SSSI), a clinically meaningful reduction in pain (≥30% based on VAS), maintenance in function (FAAM), and a safety component defined as presence versus absence of any of an a priori selected set of device-specific radiographic findings.

The safety of the Cartiva SCI device was assessed by comparison to the arthrodesis control group with respect to the nature and frequency of adverse events (overall and in terms of seriousness and relationship to the implant/procedure), the need for subsequent secondary surgical intervention, and presence versus absence of any of an a priori selected set of radiographic findings.

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# Study Protocol Pre-specified Endpoint

The pre-specified primary endpoint of the study was individual subject success defined as follows:

- Improvement (decrease) from baseline in VAS Pain of ≥30% at 12 months;⁵
- Maintenance of function from baseline in FAAM Sports score (inclusive of decrease &lt;9) at 12 months; and,⁶
- Freedom from major complications⁷ and SSSIs through 24 months.
- No radiographic failure, which for each arm is defined separately:
- Cartiva SCI - device displacement, device fragmentation, and/or development of avascular necrosis
- Arthrodesis - mal-union, non-union, and/or hardware failure. The radiographic assessment for non-union and mal-union will only be included from 3 months to 24 months after surgery.

# Revised Primary Endpoint

After review of the data submitted in the PMA, FDA requested additional analysis using a revised primary endpoint. The FDA requested revised endpoint is similar to the pre-specified composite endpoint with the following differences: 1) evaluate all efficacy outcomes at 24 months and 2) evaluate the FAAM ADL subscale instead of the FAAM Sports subscale. There were no changes to the definition of the safety prong.

The revised composite endpoint was defined as follows:

- Improvement (decrease) from baseline in VAS Pain of ≥30% at 24 months;
- Maintenance in function from baseline in FAAM ADL score (inclusive of decrease &lt;8) at 24 months; and,
- Freedom from major complications⁸ and SSSIs through 24 months
- No radiographic failure, which for each arm was defined separately as:
- Cartiva SCI: device displacement, device fragmentation, and/or development of avascular necrosis

⁵ The criterion for the success for pain was based on the work conducted by Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus group. Dworkin and the IMMPACT consensus group evaluated the level of improvement in pain reported in clinical studies and recommended that a decrease in pain of ≥30% be reported in future clinical trials. This level of response was defined as a clinically important change and represented a moderate level of improvement.

⁶ Martin et al. reported in the validation of the Foot and Ankle Mobility Scale (FAAM) that 9 points was the minimal clinically important difference in the Sports subscale and 8 points in the ADL subscale. The individual success criterion for the function component ensures there is no clinically significant worsening in function in order for subjects to be considered a responder in the primary endpoint.

⁷ Major complications were defined from radiographic findings and were assessed by an independent radiographic reviewer. These included absence of device displacement, device fragmentation, and avascular necrosis in the Cartiva group and the absence of mal-union, non-union, and hardware fractures in the control (arthrodesis) group.

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○ Arthrodesis: mal-union, non-union, and/or hardware failure. The radiographic assessment for non-union and mal-union will only be included from 3 months to 24 months after surgery.

The proportion of successes in each group was determined and the difference (Cartiva minus arthrodesis) and one-sided 95% confidence interval for the difference between treatment groups was calculated. If the one-sided 95% lower confidence interval is greater than the equivalence limit (-15%), the primary endpoint will have been met.

## Secondary Endpoints and Assessments

Secondary endpoints, measured in both treatment groups, included VAS Pain scores, FAAM Sports and ADL scores, range of motion as assessed by active MTP peak dorsiflexion, subject satisfaction, SF-36 Physical Functioning Scale, and FFI-R.

Other radiographic findings beyond the assessments included in the primary endpoint analysis were evaluated to determine their effect on subject outcomes.

## B. ACCOUNTABILITY OF PMA COHORT

A total of 236 subjects were enrolled including n=17 subjects who withdrew prior to randomization, n=22 non-randomized roll-in subjects, and 197 randomized subjects (132 to Cartiva SCI device and 65 to arthrodesis). Among randomized subjects, 2 of 132 (1.5%) subjects randomized to the Cartiva SCI device withdrew prior to receiving treatment, as did 15 of 65 (23.1%) subjects randomized to arthrodesis, leaving 130 and 50 subjects, respectively, included in the Cartiva SCI device and arthrodesis mITT analysis set. The primary reason associated with withdrawal prior to treatment (66.7%) were subjects randomized to arthrodesis who wanted the Cartiva SCI device. The total number of treated Cartiva SCI device subjects included in the Safety Analysis was 152 including 22 non-randomized roll-in subjects. A summary of subject accountability data is provided in Figure 2 and Table 6 below.

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Figure 2: Subject Accountability Tree

Table 6: MOTION Study Cumulative Randomized Implanted Subjects Accountability by Visit (mITT Cohort)

| | Pre-Op | | Week 6 | | Month 3 | | Month 6 | | Month 12 | | Month 24 | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | I | C | I | C | I | C | I | C | I | C | I | C |
| (1) Theoretical follow-up | 130 | 50 | 130 | 50 | 130 | 50 | 130 | 50 | 130 | 50 | 130 | 50 |
| (2) Cumulative deaths | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| (3) Cumulative (Terminal) Failures | 0 | 0 | 1 | 0 | 2 | 2 | 2 | 3 | 7 | 4 | 13 | 6 |
| (4) Deaths+Failures among theoretical due | 0 | 0 | 1 | 0 | 2 | 2 | 2 | 3 | 7 | 4 | 13 | 6 |
| (5) Expected due for clinic visit | 130 | 50 | 129 | 50 | 128 | 48 | 128 | 47 | 123 | 46 | 117 | 44 |
| (6) Failures among theoretical due | 0 | 0 | 1 | 0 | 2 | 2 | 2 | 3 | 7 | 4 | 13 | 6 |
| (7) Expected due+Failures among theoretical due | 130 | 50 | 130 | 50 | 130 | 50 | 130 | 50 | 130 | 50 | 130 | 50 |
| All Evaluated Accounting (Actual1) Among Expected Due Procedures | | | | | | | | | | | | |
| | I | C | I | C | I | C | I | C | I | C | I | C |
| (8) FAAM ADL Follow-up (9) / (5) (%) | 99.2% | 100% | 96.90% | 96.00% | 97.70% | 95.80% | 95.30% | 91.50% | 99.20% | 93.50% | 98.30% | 93.20% |
| (9) Change from baseline in FAAM ADL available | 129 | 50 | 125 | 48 | 125 | 46 | 122 | 43 | 122 | 43 | 115 | 41 |
| (10) Change from baseline in VAS Pain available | 130 | 50 | 128 | 48 | 128 | 46 | 124 | 43 | 123 | 43 | 116 | 41 |
| (11) Radiography endpoint | | | | | | | | | 130 | 50 | 130 | 50 |
| (12) CCS at Month 12 and Month 24 available | | | | | | | | | 130 | 47 | 129 | 47 |
| (13) Actual1 % Follow-up for CCS (12) / (7) | | | | | | | | | 100.00% | 94.00% | 99.20% | 94.00% |

Subjects with any follow-up data reviewed or evaluated by investigator.

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# Analysis Populations

Throughout this summary, the following terms are used to describe the populations used for analysis:

Table 7: MOTION Study Analysis Populations

| Analysis Population | Cartiva Randomized | Arthrodesis | Cartiva Roll-In | Total Subjects |
| --- | --- | --- | --- | --- |
| Safety1 | 130 | 50 | 22 | 202 |
| ITT2 | 132 | 65 | - | 197 |
| mITT3 | 130 | 50 | - | 180 |
| mITT Completers4 | 129 | 47 | - | 176 |
| Per Protocol (PP)5 | 127 | 47 | - | 174 |

1The Safety population includes all treated subjects.
2The ITT population includes all randomized subjects. Subjects who dropped out prior to treatment are considered study failures.
3The mITT population includes all randomized subjects who received the treatment to which they were randomized.
4The mITT completers population includes all randomized subjects who received the treatment to which they were randomized and have 24M data available.
5The PP population includes all randomized subjects who received the treatment to which they were randomized with subjects having major inclusion/exclusion deviations excluded.

# C. STUDY POPULATION DEMOGRAPHICS AND BASELINE PARAMETERS

Subject demographics are summarized below in Table 8. These data show that the treatment groups were well balanced and no statistically significant differences were noted. The baseline demographics of the study population are consistent with baseline demographics reported in the literature for hallux rigidus subjects treated with cheilectomy, hemiarthroplasty, and/or arthrodesis. The majority (80%) of the subjects enrolled in the study were females, consistent with the literature that shows that women have a higher incidence of MTP osteoarthritis compared to men. The majority of MOTION subjects treated (77%) presented with angular alignment of the first metatarsophalangeal joint, within a normal range (less than $15^{\circ}$ ) and 23% presented with angular deformity of the first metatarsophalangeal joint between $15^{\circ}-20^{\circ}$ (mild hallux valgus) Table 11.

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Table 8: MOTION Study Subject Baseline Characteristics (Continuous Variables, mITT Cohort)

| | Cartiva (N=130) | | | Arthrodesis (N=50) | | | t-test p-value1 |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Demographics - All | Mean | SD | Med | Mean | SD | Med | |
| Age at surgery (yrs) | 57.4 | 8.8 | 57.9 | 54.9 | 10.5 | 55.1 | 0.115 |
| Height (cm) | 165.9 | 7.8 | 165.0 | 167.4 | 9.4 | 165.6 | 0.293 |
| Weight (kg) | 75.1 | 14.5 | 72.7 | 73.7 | 15.5 | 71.0 | 0.591 |
| BMI (k/m2) | 27.2 | 4.4 | 26.5 | 26.3 | 4.7 | 25.7 | 0.222 |
| Baseline Functional Status | | | | | | | |
| FAAM ADL | 59.4 | 16.9 | 58.3 | 56.0 | 16.8 | 54.9 | 0.222 |
| FAAM Sports | 36.9 | 20.9 | 34.4 | 35.6 | 20.5 | 31.3 | 0.694 |
| SF36 | 52.4 | 22.8 | 50.0 | 49.8 | 23.6 | 40.0 | 0.499 |
| VAS | 68.0 | 13.9 | 68.3 | 69.3 | 14.3 | 70.0 | 0.571 |

Two sample Pooled t-test p-value.

Table 9: MOTION Study Subject Baseline Characteristics (Categorical Variables, mITT Cohort)

| | Cartiva | | Arthrodesis | | p-value1 |
| --- | --- | --- | --- | --- | --- |
| Gender | n | % | N | % | |
| Male | 26 | 20.0% | 12 | 24.0% | 0.547 |
| Female | 104 | 80.0% | 38 | 76.0% | |

Two sample Pooled t-test p-value.

Table 10: MOTION Study Subject Baseline Characteristics - Grade of Hallux Rigidus² (ITT)

| Categorical Variables | Cartiva (N=132) | | Arthrodesis (N=65)² | | p-value¹ |
| --- | --- | --- | --- | --- | --- |
| | n | % | n | % | |
| Grade | | | | | 0.3418 |
| 2 | 37 | 28.03 | 21 | 32.81 | |
| 3 | 74 | 56.06 | 29 | 45.31 | |
| 4 | 21 | 15.91 | 14 | 21.88 | |

Two-sided Fisher's exact test.
²One arthrodesis patient did not have a baseline OA grade

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Table 11: MOTION Study Subjects Baseline Characteristics – Angular Deformities Involving the First Metatarsophalangeal Joint (Normal and Mild Hallux Valgus)

| Angular Deformity | n | N | % |
| --- | --- | --- | --- |
| 0 to 15°
Normal | 155 | 202 | 77% |
| ≥ 15 to 20°
Mild Hallux Valgus | 47 | 202 | 23% |

D. PERI-OPERATIVE INFORMATION

Surgical timing information was available for 112 (74% of treated) Cartiva SCI device subjects and 39 (78% of treated) arthrodesis subjects, and length of anesthesia information was available for 137 (90%) Cartiva SCI device subjects and 44 (88%) arthrodesis subjects (Table 12).

Table 12: Length of Surgical Procedure and Anesthesia (minutes) for the Safety Cohort

| | Cartiva | | | Arthrodesis | | | p-value |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | N | Mean | SD | N | Mean | SD | |
| Procedure Time (minutes) | 112 | 34.7 | 12.3 | 39 | 57.8 | 21.5 | <0.001 |
| Length of Anesthesia (minutes) | 137 | 67.0 | 27.8 | 44 | 95.3 | 41.1 | <0.001 |

The Cartiva SCI device surgical implantation procedure time is, on average, 40% shorter (23 minutes) than arthrodesis. Due to the shorter surgical procedure, as expected, the length of anesthesia administration for Cartiva SCI device subjects was, on average, 28 minutes shorter than that for arthrodesis subjects (p&lt;0.001).

There were no significant differences observed in the type of anesthesia regimen with 92% of subjects in both treatment arms receiving general IV sedation combined with a regional ankle nerve block anesthetic.

E. SAFETY AND EFFECTIVENESS RESULTS

Safety

The analysis of safety was based on the Safety Cohort of 202 total subjects treated (22 Cartiva SCI device roll-in subjects, 130 randomized and treated Cartiva SCI device subjects, and 50 arthrodesis control subjects).

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Adverse events were classified by the Investigator for relationship to the device, severity, and for seriousness of the event. The overall adverse event rate was similar for the Cartiva SCI device group (69.1%) and the arthrodesis control group (72.0%). The majority of the events were mild or moderate in nature as classified by the Investigator for the Cartiva SCI device subjects (86.2%) and arthrodesis control group (78.0%).

Table 13: Summary of Adverse Event Experiences - Safety Analysis Set

| | Cartiva (N = 152) | | | Fusion (N = 50) | | | Cartiva vs Fusion | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Events | n | % | Events | n | % | Diff | LB1 | UB1 | p-value2 |
| Any adverse event | 245 | 105 | 69.1% | 72 | 36 | 72.0% | -2.9% | -18.8% | 12.9% | 0.727 |
| Treatment Emergent Event | 102 | 67 | 44.1% | 32 | 21 | 42.0% | 2.1% | -14.0% | 18.1% | 0.870 |
| Device Related Event | 31 | 23 | 15.1% | 4 | 4 | 8.0% | 7.1% | -9.0% | 23.0% | 0.238 |
| Operative Procedure Related Event | 71 | 51 | 33.6% | 28 | 18 | 36.0% | -2.4% | -18.2% | 13.5% | 0.864 |
| Non-Treatment Emergent Event | 143 | 73 | 48.0% | 40 | 26 | 52.0% | -4.0% | -20.0% | 12.2% | 0.745 |
| Any Serious adverse event | 37 | 30 | 19.7% | 12 | 9 | 18.0% | 1.7% | -14.2% | 17.5% | 0.999 |
| Treatment Emergent Event | 17 | 17 | 11.2% | 4 | 4 | 8.0% | 3.2% | -12.9% | 19.2% | 0.605 |
| Device Related Event | 11 | 11 | 7.2% | 2 | 2 | 4.0% | 3.2% | -12.9% | 19.3% | 0.526 |
| Operative Procedure Related Event | 6 | 6 | 3.9% | 2 | 2 | 4.0% | -0.1% | -16.2% | 16.1% | 0.999 |
| Non-Treatment Emergent Event | 20 | 14 | 9.2% | 8 | 5 | 10.0% | -0.8% | -16.8% | 15.2% | 0.999 |
| AE by Severity | | | | | | | | | | |
| Mild | 110 | 70 | 46.1% | 41 | 25 | 50.0% | -3.9% | -20.0% | 12.2% | 0.744 |
| Moderate | 114 | 61 | 40.1% | 26 | 14 | 28.0% | 12.1% | -3.7% | 27.8% | 0.133 |
| Severe | 21 | 16 | 10.5% | 5 | 5 | 10.0% | 0.5% | -15.5% | 16.5% | 0.999 |
| AE Resolution Status | | | | | | | | | | |
| Resolved without Sequelae | 145 | 76 | 50.0% | 48 | 26 | 52.0% | -2.0% | -18.1% | 14.2% | 0.871 |
| Resolved with Sequelae | 9 | 8 | 5.3% | 3 | 2 | 4.0% | 1.3% | -14.9% | 17.4% | 0.999 |
| Unresolved at Study Exit / Completion | 87 | 55 | 36.2% | 21 | 17 | 34.0% | 2.2% | -13.5% | 18.1% | 0.865 |
| Unknown | 1 | 1 | 0.7% | 0 | 0 | 0.0% | 0.7% | -15.5% | 16.8% | 0.999 |
| Other | 2 | 2 | 1.3% | 0 | 0 | 0.0% | 1.3% | -14.8% | 17.4% | 0.999 |
| Anticipated Events | 100 | 66 | 43.4% | 28 | 19 | 38.0% | 5.4% | -10.6% | 21.3% | 0.515 |
| Unanticipated Events | 145 | 73 | 48.0% | 44 | 27 | 54.0% | -6.0% | -22.0% | 10.2% | 0.516 |
| Notes:1 Lower and upper bounds of exact 95% confidence interval for the group difference in percentages experiencing the event.2 Fisher's Exact Test | | | | | | | | | | |

There were no statistically significant differences with respect to total adverse events, treatment emergent (device and operative related) adverse events (AEs), or Serious Adverse Events (SAEs).

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# All Adverse Events

All adverse events, as shown in Table 14 below, are reported from the "Safety Population", which included 152 Cartiva patients and 50 arthrodesis patients enrolled in the multi-center clinical study. Adverse event rates presented are based on the number of patients having at least one occurrence for a particular adverse event divided by the total number of patients in that treatment group.

A total of 105 Cartiva patients (69.1%) had at least one adverse event within 24 months versus 36 arthrodesis patients (72.0%). A total of 245 events were reported in 105 Cartiva patients and 72 events were reported in 36 arthrodesis patients. The summary of AEs by System Organ Class (SOC) and Preferred Term (PT) in either treatment group is provided in the table below reported as number of events and number of patients in the safety population.

Table 14: Adverse Events by System Organ Class, Preferred Term, and Treatment Group

| | Cartiva (N = 152) | | | Fusion (N = 50) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Events | Subj. | % | Events | Subj. | % |
| BLOOD AND LYMPHATIC SYSTEM DISORDERS | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Splenomegaly | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| CARDIAC DISORDERS | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Aortic valve stenosis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Aortic valve disease | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| CONGENITAL, FAMILIAL, AND GENETIC DISORDERS | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Congenital foot malformation | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| EAR AND LABYRINTH DISORDERS | 2 | 1 | 0.7% | 0 | 0 | 0.0% |
| Eustachian tube patulous | 2 | 1 | 0.7% | 0 | 0 | 0.0% |
| ENDOCRINE DISORDERS | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Hypothyroidism | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| GASTROINTESTINAL DISORDERS | 6 | 6 | 3.9% | 1 | 1 | 2.0% |
| Abdominal pain upper | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Diverticulum | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Gastrointestinal pain | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Salivary gland calculus | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Small intestinal obstruction | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Tongue oedema | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 28 | 23 | 15.1% | 2 | 2 | 4.0% |
| Fibrosis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Gait disturbance | 3 | 2 | 1.3% | 0 | 0 | 0.0% |
| Impaired healing | 1 | 1 | 0.7% | 1 | 1 | 2.0% |

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| | Cartiva (N = 152) | | | Fusion (N = 50) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Events | Subj. | % | Events | Subj. | % |
| Oedema peripheral | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Non-cardiac chest pain | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Implant site pain | 18 | 16 | 10.5% | 0 | 0 | 0.0% |
| Implant site cyst | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Implant site induration | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Implant site swelling | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| HEPATOBILIARY DISORDERS | 3 | 3 | 2.0% | 0 | 0 | 0.0% |
| Cholecystitis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Cholecystitis acute | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Hepatomegaly | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| INFECTIONS AND INFESTATIONS | 13 | 12 | 7.9% | 7 | 5 | 10.0% |
| Arthritis viral | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Bronchitis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Clostridium difficile colitis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Cystitis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Herpes zoster | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Influenza | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Nasopharyngitis | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Onychomycosis | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Pneumonia | 1 | 1 | 0.7% | 1 | 1 | 2.0% |
| Postoperative wound infection | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Sepsis | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Sinusitis | 1 | 1 | 0.7% | 1 | 1 | 2.0% |
| Stitch abscess | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Urinary tract infection | 1 | 1 | 0.7% | 3 | 2 | 4.0% |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS | 86 | 57 | 37.5% | 31 | 21 | 42.0% |
| Ankle fracture | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Back injury | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Device breakage | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Device migration | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Fall | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Foot fracture | 6 | 5 | 3.3% | 1 | 1 | 2.0% |
| Hand fracture | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Humerus fracture | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Joint sprain | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Road traffic accident | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Spinal cord injury | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Tendon rupture | 1 | 1 | 0.7% | 0 | 0 | 0.0% |

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| | Cartiva (N = 152) | | | Fusion (N = 50) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Events | Subj. | % | Events | Subj. | % |
| Muscle strain | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Contusion | 1 | 1 | 0.7% | 1 | 1 | 2.0% |
| Comminuted fracture | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Meniscus lesion | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Medical device complication | 0 | 0 | 0.0% | 4 | 4 | 8.0% |
| Post procedural bile leak | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Post procedural discharge | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Post procedural complication | 1 | 1 | 0.7% | 1 | 1 | 2.0% |
| Medical device pain | 6 | 6 | 3.9% | 2 | 2 | 4.0% |
| Joint injury | 5 | 4 | 2.6% | 2 | 1 | 2.0% |
| Limb injury | 2 | 1 | 0.7% | 3 | 2 | 4.0% |
| Skeletal injury | 2 | 1 | 0.7% | 0 | 0 | 0.0% |
| Postoperative wound complication | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Post procedural oedema | 3 | 3 | 2.0% | 2 | 2 | 4.0% |
| Limb crushing injury | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Procedural pain | 31 | 29 | 19.1% | 9 | 9 | 18.0% |
| Avulsion fracture | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Post procedural swelling | 11 | 10 | 6.6% | 3 | 3 | 6.0% |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | 68 | 46 | 30.3% | 20 | 16 | 32.0% |
| Arthralgia | 16 | 15 | 9.9% | 3 | 3 | 6.0% |
| Arthritis | 4 | 4 | 2.6% | 3 | 2 | 4.0% |
| Arthropathy | 2 | 1 | 0.7% | 0 | 0 | 0.0% |
| Back pain | 1 | 1 | 0.7% | 2 | 2 | 4.0% |
| Bone cyst | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Bunion | 2 | 2 | 1.3% | 1 | 1 | 2.0% |
| Bursitis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Cervical spinal stenosis | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Exostosis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Fracture nonunion | 0 | 0 | 0.0% | 2 | 2 | 4.0% |
| Joint stiffness | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Metatarsalgia | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Monarthritis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Muscle spasms | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Musculoskeletal pain | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Osteoarthritis | 7 | 4 | 2.6% | 1 | 1 | 2.0% |
| Pain in extremity | 11 | 10 | 6.6% | 1 | 1 | 2.0% |
| Palindromic rheumatism | 1 | 1 | 0.7% | 0 | 0 | 0.0% |

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| | Cartiva (N = 152) | | | Fusion (N = 50) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Events | Subj. | % | Events | Subj. | % |
| Plantar fasciitis | 2 | 2 | 1.3% | 1 | 1 | 2.0% |
| Spinal column stenosis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Tendonitis | 3 | 2 | 1.3% | 1 | 1 | 2.0% |
| Fibromyalgia | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Muscle tightness | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Joint crepitation | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Foot deformity | 7 | 6 | 3.9% | 1 | 1 | 2.0% |
| Limb discomfort | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| NEOPLASMS BENIGN, MALIGNANT, AND UNSPECIFIED (INCL CYSTS AND POLYPS) | 6 | 5 | 3.3% | 2 | 2 | 4.0% |
| B-cell lymphoma | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Neuroma | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Throat cancer | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Gastrointestinal stromal tumor | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Prostate cancer | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Benign soft tissue neoplasm | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Benign muscle neoplasm | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| NERVOUS SYSTEM DISORDERS | 5 | 5 | 3.3% | 2 | 1 | 2.0% |
| Carpal tunnel syndrome | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Dysaesthesia | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Hypoaesthesia | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Neuralgia | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Neuropathy peripheral | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Syncope | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Cognitive disorder | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| PREGNANCY, PUERPERIUM AND PERINATAL CONDITIONS | 1 | 1 | 0.7% | 1 | 1 | 2.0% |
| Pregnancy | 1 | 1 | 0.7% | 1 | 1 | 2.0% |
| PSYCHIATRIC DISORDERS | 5 | 5 | 3.3% | 1 | 1 | 2.0% |
| Anxiety | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Depression | 2 | 2 | 1.3% | 1 | 1 | 2.0% |
| Insomnia | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| RENAL AND URINARY DISORDERS | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Nephrolithiasis | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| REPRODUCTIVE SYSTEM AND BREAST DISORDERS | 1 | 1 | 0.7% | 1 | 1 | 2.0% |
| Metrorrhagia | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Postmenopausal hemorrhage | 1 | 1 | 0.7% | 0 | 0 | 0.0% |

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| | Cartiva (N = 152) | | | Fusion (N = 50) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Events | Subj. | % | Events | Subj. | % |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | 4 | 3 | 2.0% | 0 | 0 | 0.0% |
| Dysphonia | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Dyspnoea | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Nasal septum deviation | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Sleep apnoea syndrome | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | 6 | 5 | 3.3% | 2 | 2 | 4.0% |
| Dyshidrosis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Ingrowing nail | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Rash | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Scar | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Skin disorder | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Skin lesion | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Skin ulcer | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| SURGICAL AND MEDICAL PROCEDURES | 3 | 3 | 2.0% | 1 | 1 | 2.0% |
| Bunion operation | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Hip Arthroplasty | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Hysterectomy | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Muscle operation | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| VASCULAR DISORDERS | 3 | 3 | 2.0% | 0 | 0 | 0.0% |
| Hypertension | 3 | 3 | 2.0% | 0 | 0 | 0.0% |

From the table above, there are three categories of adverse events for Preferred Term in which the Cartiva SCI device group is greater than or equal to approximately $4\%$ points higher for the number of subjects in the study experiencing these adverse events than compared to the arthrodesis group. These PT categories include: Implant site pain (10.5% vs 0%); Arthralgia (9.9% vs 6.0%); and Pain in the Extremity (6.6% vs 2.0%). Specifically, a higher percentage of Cartiva SCI device subjects had adverse events involving pain. The correlation between subjects with high rates of pain adverse events and primary outcome measures for device effectiveness were seen in 8 out of 16 subjects with device related pain events that were counted as overall successes.

There were two PT categories where the number of subjects experiencing an adverse event was greater in the arthrodesis group: Fracture Non-union (4.0% vs 0%), Medical Device Breakage (2.0% vs 0%), and Medical Device Complications (8.0% vs 0%), which also is defined as including non-union and delayed union for the arthrodesis group.

Among the SOC categories, there are a greater percentage of Cartiva SCI device subjects (15.1% vs 4.0%) who experienced “General Disorders and Administration Site Conditions.” The PT

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categories under this SOC category shows that there were a greater percentage of Cartiva SCI device subject were observed with Implant Site Pain (10.5% vs 0%), Gait Disturbance (1.3% vs 0%), and Implant Site Swelling (1.3% vs 0%).

Table 15 below provides all Adverse Events by time course.

Table 15: Counts of Adverse Events by Time Interval in Cartiva (I) and Arthrodesis (C) Safety Analysis Sets

| | Immed Post-Op | | 1 mo | | 3 mo | | 6 mo | | 12 mo | | 24 mo | | 24+mo | | Total Events | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | I | C | I | C | I | C | I | C | I | C | I | C | I | C | I | C |
| BLOOD AND LYMPHATIC SYSTEM DISORDERS | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Splenomegaly | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| CARDIAC DISORDERS | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Aortic valve stenosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Aortic valve disease | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| CONGENITAL, FAMILIAL, AND GENETIC DISORDERS | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Congenital foot malformation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| EAR AND LABYRINTH DISORDERS | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 2 | 0 |
| Eustachian tube patulous | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 2 | 0 |
| ENDOCRINE DISORDERS | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Hypothyroidism | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| GASTROINTESTINAL DISORDERS | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 3 | 0 | 1 | 1 | 1 | 0 | 6 | 1 |
| Abdominal pain upper | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
| Diverticulum | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Gastrointestinal pain | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Salivary gland calculus | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Small intestinal obstruction | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Tongue oedema | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 1 | 0 | 2 | 1 | 7 | 0 | 7 | 0 | 7 | 1 | 2 | 0 | 2 | 0 | 28 | 2 |
| Fibrosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Gait disturbance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 3 | 0 |
| Impaired healing | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Oedema peripheral | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Non-cardiac chest pain | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Implant site pain | 0 | 0 | 1 | 0 | 6 | 0 | 6 | 0 | 4 | 0 | 1 | 0 | 0 | 0 | 18 | 0 |
| Implant site cyst | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Implant site induration | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Implant site swelling | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |

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| | Immed Post-Op | | 1 mo | | 3 mo | | 6 mo | | 12 mo | | 24 mo | | 24+mo | | Total Events | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | I | C | I | C | I | C | I | C | I | C | I | C | I | C | I | C |
| HEPATOBILIARY DISORDERS | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 3 | 0 |
| Cholecystitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Cholecystitis acute | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Hepatomegaly | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| INFECTIONS AND INFESTATIONS | 0 | 0 | 1 | 1 | 5 | 3 | 1 | 2 | 3 | 1 | 3 | 0 | 0 | 0 | 13 | 7 |
| Arthritis viral | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Bronchitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Clostridium difficile colitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Cystitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Herpes zoster | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Influenza | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Nasopharyngitis | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
| Onychomycosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Pneumonia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Postoperative wound infection | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Sepsis | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Sinusitis | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Stitch abscess | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Urinary tract infection | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 3 |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS | 3 | 0 | 1 | 2 | 17 | 11 | 16 | 9 | 23 | 6 | 24 | 3 | 2 | 0 | 86 | 31 |
| Ankle fracture | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Back injury | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Device breakage | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Device migration | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Fall | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Foot fracture | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 1 | 1 | 0 | 1 | 0 | 6 | 1 |
| Hand fracture | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Humerus fracture | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Joint sprain | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Road traffic accident | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Spinal cord injury | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Tendon rupture | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Muscle strain | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Contusion | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 |
| Comminuted fracture | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Meniscus lesion | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |

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| | Immed Post-Op | | 1 mo | | 3 mo | | 6 mo | | 12 mo | | 24 mo | | 24+mo | | Total Events | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | I | C | I | C | I | C | I | C | I | C | I | C | I | C | I | C |
| Medical device complication | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 4 |
| Post procedural bile leak | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Post procedural discharge | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Post procedural complication | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 |
| Medical device pain | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 2 | 0 | 1 | 0 | 6 | 2 |
| Joint injury | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 3 | 0 | 0 | 0 | 5 | 2 |
| Limb injury | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 2 | 3 |
| Skeletal injury | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Postoperative wound complication | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Post procedural oedema | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 2 |
| Limb crushing injury | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Procedural pain | 0 | 0 | 0 | 1 | 8 | 4 | 6 | 2 | 8 | 1 | 9 | 1 | 0 | 0 | 31 | 9 |
| Avulsion fracture | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Post procedural swelling | 0 | 0 | 0 | 0 | 3 | 2 | 5 | 0 | 1 | 1 | 2 | 0 | 0 | 0 | 11 | 3 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | 3 | 0 | 3 | 0 | 9 | 2 | 4 | 0 | 22 | 4 | 20 | 11 | 7 | 3 | 68 | 20 |
| Arthralgia | 1 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 7 | 0 | 4 | 3 | 0 | 0 | 16 | 3 |
| Arthritis | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 2 | 4 | 3 |
| Arthropathy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Back pain | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 1 | 2 |
| Bone cyst | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Bunion | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 2 | 1 |
| Bursitis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Cervical spinal stenosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Exostosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Fracture nonunion | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 |
| Joint stiffness | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Metatarsalgia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Monarthritis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Muscle spasms | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Musculoskeletal pain | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Osteoarthritis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 7 | 0 | 0 | 1 | 7 | 1 |
| Pain in extremity | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 4 | 0 | 3 | 1 | 2 | 0 | 11 | 1 |
| Palindromic rheumatism | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Plantar fasciitis | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 2 | 1 |
| Spinal column stenosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Tendonitis | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 3 | 1 |

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| | Immed Post-Op | | 1 mo | | 3 mo | | 6 mo | | 12 mo | | 24 mo | | 24+mo | | Total Events | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | I | C | I | C | I | C | I | C | I | C | I | C | I | C | I | C |
| Fibromyalgia | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Muscle tightness | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Joint crepitation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Foot deformity | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 2 | 1 | 1 | 0 | 7 | 1 |
| Limb discomfort | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| NEOPLASMS BENIGN, MALIGNANT, AND UNSPECIFIED (INCL CYSTS AND POLYPS) | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 4 | 1 | 0 | 0 | 6 | 2 |
| B-cell lymphoma | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Neuroma | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Throat cancer | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Gastrointestinal stromal tumour | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Prostate cancer | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
| Benign soft tissue neoplasm | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Benign muscle neoplasm | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| NERVOUS SYSTEM DISORDERS | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 5 | 2 |
| Carpal tunnel syndrome | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Dysaesthesia | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Hypoaesthesia | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Neuralgia | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Neuropathy peripheral | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Syncope | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Cognitive disorder | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| PREGNANCY, PUERPERIUM AND PERINATAL CONDITIONS | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 1 |
| Pregnancy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 1 |
| PSYCHIATRIC DISORDERS | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 2 | 0 | 0 | 0 | 5 | 1 |
| Anxiety | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Depression | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 2 | 1 |
| Insomnia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| RENAL AND URINARY DISORDERS | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Nephrolithiasis | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| REPRODUCTIVE SYSTEM AND BREAST DISORDERS | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 1 |
| Metrorrhagia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Postmenopausal haemorrhage | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 4 | 0 |
| Dysphonia | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |

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| | Immed Post-Op | | 1 mo | | 3 mo | | 6 mo | | 12 mo | | 24 mo | | 24+mo | | Total Events | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | I | C | I | C | I | C | I | C | I | C | I | C | I | C | I | C |
| Dyspnoea | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Nasal septum deviation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Sleep apnoea syndrome | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 2 | 1 | 2 | 1 | 0 | 0 | 6 | 2 |
| Dyshidrosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Ingrowing nail | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Rash | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 0 |
| Scar | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Skin disorder | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Skin lesion | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Skin ulcer | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| SURGICAL AND MEDICAL PROCEDURES | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 3 | 1 |
| Bunion operation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Hip Arthroplasty | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Hysterectomy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Muscle operation | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| VASCULAR DISORDERS | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 3 | 0 |
| Hypertension | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 3 | 0 |

The verbatim event term for the event device migration in the Cartiva group indicated the device shifted within the implant cavity. The device did not migrate outside of the cavity or dislodge the cavity or joint. This event was not observed by the independent radiographic reviewer and did not correlate to any independent radiographic findings.

## Serious Adverse Events

A summary of the total number of Serious Adverse Events (SAE) is shown in Table 16. To evaluate that Cartiva SCI device is safe, the company collected all adverse event data and had safety data reviewed by the Medical Monitor. A SAE was defined as follows: 1) death or threat to life; or, 2) permanent impairment of a body function or permanent damage to a body structure; or, 3) an event requiring medical or surgical intervention to preclude permanent impairment of a body function or permanent damage to a body structure. During the MOTION study, there were a total of 37 SAEs in 30 subjects (19.7%) in the Cartiva SCI device arm and 12 serious adverse events in 9 subjects (18.0%) in the arthrodesis arm.

PMA P150017: FDA Summary of Safety and Effectiveness Data

{31}

Table 16: Serious Adverse Events by System Organ Class, Preferred Term, and Treatment Group - Safety Analysis Set

| | Cartiva (N = 152) | | | Fusion (N = 50) | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Events | Subj. | % | Events | Subj. | % |
| CARDIAC DISORDERS | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Aortic valve stenosis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| CONGENITAL, FAMILIAL, AND GENETIC DISORDERS | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Congenital foot malformation | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| EAR AND LABYRINTH DISORDERS | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Eustachian tube patulous | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| GASTROINTESTINAL DISORDERS | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Small intestinal obstruction | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | 9 | 9 | 5.9% | 0 | 0 | 0.0% |
| Fibrosis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Implant site pain | 8 | 8 | 5.3% | 0 | 0 | 0.0% |
| HEPATOBILIARY DISORDERS | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| Cholecystitis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Cholecystitis acute | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| INFECTIONS AND INFESTATIONS | 1 | 1 | 0.7% | 3 | 1 | 2.0% |
| Postoperative wound infection | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Sepsis | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Urinary tract infection | 0 | 0 | 0.0% | 2 | 1 | 2.0% |
| INJURY, POISONING AND PROCEDURAL COMPLICATIONS | 8 | 8 | 5.3% | 4 | 4 | 8.0% |
| Ankle fracture | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Tendon rupture | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Medical device complication | 0 | 0 | 0.0% | 2 | 2 | 4.0% |
| Post procedural bile leak | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Post procedural complication | 0 | 0 | 0.0% | 1 | 1 | 2.0% |
| Medical device pain | 3 | 3 | 2.0% | 1 | 1 | 2.0% |
| Procedural pain | 2 | 2 | 1.3% | 0 | 0 | 0.0% |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | 7 | 5 | 3.3% | 3 | 3 | 6.0% |
| Arthralgia | 1 | 1 | 0.7% | 1 | 1 | 2.0% |
| Arthritis | 3 | 3 | 2.0% | 1 | 1 | 2.0% |
| Joint stiffness | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Osteoarthritis | 1 | 1 | 0.7% | 0 | 0 | 0.0% |
| Foot deformity | 1 | 1 | 0.7% | 1 | 1 | 2.0% |

PMA P150017: FDA Summary of Sa…