← Product Code [MRA](/productcode/MRA) · P070026S004

# DEPUY CERAMAX CERAMIC TOTAL HIP SYSTEM (P070026S004)

_DePuy Orthopaedics, Inc. · MRA · Apr 2, 2013 · Orthopedic · APPR_

**Canonical URL:** https://fda-staging.innolitics.com/device/P070026S004

## Device Facts

- **Applicant:** DePuy Orthopaedics, Inc.
- **Product Code:** [MRA](/productcode/MRA.md)
- **Decision Date:** Apr 2, 2013
- **Decision:** APPR
- **Device Class:** Class 3
- **Review Panel:** Orthopedic
- **Attributes:** Therapeutic, Real-World Evidence

## Real-World Evidence

| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
| --- | --- | --- | --- | --- | --- |
| P070026S004 · Apr 2, 2013 | DEPUY CERAMAX CERAMIC TOTAL HIP SYSTEM | DePuy Orthopaedics, Inc. | UK National Joint Registry (UK NJR); Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) | The FDA mandated the use of national joint registry data as a post-approval study to monitor long-term device survivorship and safety performance in a real-world clinical setting. | Joint Registry; Post-approval study; Device survivorship; Long-term safety |

### Clinical Evidence

| Study Design | Population | Comparator | Key Endpoints |
| --- | --- | --- | --- |
| COC36 PAS: UK & Australian National Joint Registry Data; Retrospective and prospective registry analysis; Follow-up/Duration: 10 years post-op follow-up | Patients implanted with the 36mm Ceramax® Ceramic on Ceramic Total Hip System; Number of Sites: National registries (UK and Australia) | Not applicable for this study | Device survivorship, reasons for revisions, and revision data |

## Indications for Use

The Ceramax® Ceramic Total Hip System is indicated for noncemented use in skeletally mature individuals undergoing primary total hip replacement surgery for rehabilitation of hips damaged as a result of noninflammatory degenerative joint disease (NIDJD) or any of its composite diagnoses of osteoarthritis, avascular necrosis, and post-traumatic arthritis.

## Device Story

Modular total hip system consisting of alumina composite matrix ceramic femoral head and acetabular liner, metal acetabular shell, and titanium alloy femoral stems. Used in primary total hip replacement surgery; implanted by orthopedic surgeons. Ceramic components articulate to provide bearing surface. System includes 36mm ceramic heads and liners, Pinnacle acetabular shells, and S-ROM or Porocoat Summit femoral stems. Designed for cementless fixation. Provides stable hip joint articulation for patients with noninflammatory degenerative joint disease. Clinical output monitored via Harris Hip Score and radiographic assessment. Benefits include restoration of hip function and pain relief.

## Clinical Evidence

Prospective, multi-center, nonrandomized, controlled clinical study (IDE #G030075) comparing 36mm ceramic-on-ceramic (COC36) to 28mm ceramic-on-polyethylene (COP28) hip systems. 242 subjects enrolled. Primary endpoint: non-inferiority of Harris Hip Score (HHS) at 24+ months (5-point margin). Results: COC36 HHS mean 95.6 vs COP28 94.9 (p<0.001). Survivorship at 4.1 years was 97.5% for COC36. No statistically significant differences in adverse events, though noise-related events (clicking, squeaking) were more frequent in COC36.

## Technological Characteristics

Materials: BIOLOX delta alumina (Al2O3) matrix composite ceramic (heads/liners), Ti-6Al-4V (ASTM F620) metal shells, CP titanium beads (ASTM F1580) porous coating, titanium alloy (ASTM F136) femoral stems/screws. Modular taper-fit assembly. Sterilization: Gamma radiation (25kGy, SAL 10^-6). Connectivity: None. Form factor: Hemispherical acetabular cups, modular femoral stems, ceramic bearing couple.

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

{0}

# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

## I. GENERAL INFORMATION

Device Generic Name: Prosthesis, Total Hip System, Semi-constrained, Metal/Ceramic/Ceramic/Metal, Cemented or Uncemented

Device Trade Name: Ceramax® Ceramic Total Hip System

Device Procode: MRA

Applicant's Name and Address: DePuy Orthopaedics, Inc.
700 Orthopaedic Drive
Warsaw, Indiana 46581-0988

Date(s) of Panel Recommendation: None

Premarket Approval Application (PMA) Number: P070026/S004

Date of FDA Notice of Approval: April 2, 2013

Expedited: Not applicable

The original PMA (P070026) was approved on December 23, 2010 and is indicated for noncemented use in skeletally mature individuals undergoing primary total hip replacement surgery for rehabilitation of hips damaged as a result of noninflammatory degenerative joint disease (NIDJD) or any of its composite diagnoses of osteoarthritis, avascular necrosis, and post-traumatic arthritis. The SSED to support the indication is available on the CDRH website and is incorporated by reference here:

http://www.accessdata.fda.gov/cdrh_docs/pdf7/P070026b.pdf

The current supplement was submitted for a line extension to include the 36 Millimeter BIOLOX delta Ceramic Femoral Head and BIOLOX delta Acetabular Insert Components and Additional Pinnacle® Sector II and Pinnacle® 100 Acetabular Shells and Porocoat® Summit™ and S-ROM® Hip Femoral Prosthesis System Components

## II. INDICATIONS FOR USE

The Ceramax® Ceramic Total Hip System is indicated for noncemented use in skeletally mature individuals undergoing primary total hip replacement surgery for rehabilitation of hips damaged as a result of noninflammatory degenerative joint disease (NIDJD) or any of its composite diagnoses of osteoarthritis, avascular necrosis, and post-traumatic arthritis.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 1 of 45

{1}

### III. CONTRAINDICATIONS

Use of the DePuy Ceramax® Ceramic Total Hip System is contraindicated in the following situations:

- • Skeletally immature patients (tibial and femoral epiphyses not closed);
- • Evidence of active infections that may spread to other areas of the body (e.g., osteomyelitis, pyrogenic infection of the hip joint, overt infection, urinary tract infection, etc.);
- • The presence of any known neoplastic (tumor-causing) or metastatic (spread of cancerous cells) disease;
- • Significant neurologic or musculoskeletal disorders or diseases that may adversely affect gait, weight bearing or postoperative recovery (e.g., muscular dystrophy, multiple sclerosis);
- • Presence of highly communicable disease(s) that may limit follow-up (e.g., immunocompromised conditions, hepatitis, active tuberculosis, etc.);
- • Any condition that may interfere with postoperative recovery (e.g., Paget's disease, Charcot's disease);
- • Poor skin coverage around the hip joint;
- • Use in patients with known allergies to the implant materials;
- • Inadequate bone stock to support the device (e.g., severe osteopenia or osteoporosis).
- • Marked atrophy (muscle and/or tissue loss) or deformity in the upper femur such as a birth defect affecting the leg bones.
- • Inflammatory degenerative joint disease (like rheumatoid arthritis)
- • Joint instability

### IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the DePuy Ceramax® Ceramic Total Hip System labeling.

### V. DEVICE DESCRIPTION

The DePuy Ceramax® Ceramic Total Hip System is a modular system consisting of a ceramic on ceramic acetabular bearing couple (alumina composite matrix ceramic femoral head and alumina composite ceramic matrix acetabular liner) combined with a compatible metal shell (cup) and screws and titanium alloy femoral stems identified below. Both the femoral head and acetabular liner components are manufactured from BIOLOX *delta* alumina (Al₂O₃) matrix composite ceramic by CeramTec AG. All implantable devices are supplied sterile (see sterilization section) for single use. The 28mm BIOLOX *delta* components and corresponding components were approved in P070026. Please refer to the device description provided in the original SSED for additional details. This submission is for the addition of the 36mm BIOLOX *delta* Ceramic Femoral Head and the 36mm BIOLOX *delta* Acetabular Insert Components to the system. The 36mm femoral heads are compatible with the following femoral stems: Porocoat® Summit™ and S-ROM® Hip Femoral Prosthesis System Components. The 36mm liners are compatible with the following acetabular shells: the Pinnacle® Sector II

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 2 of 45

{2}

and the Pinnacle® 100 Acetabular Shells; Porocoat® Summit™ and S-ROM® Hip Femoral Prosthesis System Components.

### 36mm BIOLOX® delta ceramic femoral heads

The alumina composite matrix ceramic heads have an 11/13 taper and are offered in three (+0 mm, +3 mm and +6 mm) neck lengths. The 36mm alumina composite matrix ceramic heads are also available with a 12/14 taper and four (+1.5 mm, +5 mm, +8.5 mm and +12mm,) neck lengths. DePuy BIOLOX® delta ceramic femoral heads are only compatible with the DePuy femoral prostheses identified here and in Table 1.

### 36mm BIOLOX® delta ceramic liner (insert)

The alumina composite matrix ceramic acetabular liners are offered in eight sizes with an internal diameter of 36mm. The eight sizes are offered in outer diameters of 52-66 mm in 2 mm increments. A taper-fit connection allows assembly into the mating metal acetabular shell components.

### Pinnacle® acetabular cups

The Pinnacle® 100 and Pinnacle® Sector II acetabular cups are hemispherical type replacement prostheses with a single apex hole. The Sector II has three screw holes that allow for adjunctive fixation with 6.5mm diameter bone screws. The metal outer acetabular shell components are manufactured from Ti-6Al-4V (ASTM F620). A porous coating of commercially pure (CP) titanium beads (ASTM F1580) covers the outer surfaces of the shells. The metal outer shells are available with 52, 54, 56, 58, 60, 62, 64, 66 mm outer diameters.

### Bone Screws

The DePuy 6.5mm diameter cancellous bone screws are optional, and are available in titanium alloy (ASTM F136) in sizes ranging in lengths from 15-70 mm.

### DePuy Femoral Stems

The DePuy Ceramax® Ceramic Total Hip System uses the commercially available DePuy S-ROM® and Porocoat® Summit™ titanium alloy (ASTM F136) femoral stem components.

The titanium alloy femoral stems, S-ROM® with 11/13 trunnions and Porocoat® Summit™ with 12/14 trunnions, are for cementless use. The S-ROM® stems are available in standard and lateralized versions. The Summit™ stems are available with standard and high offsets. The stems are partially coated with a commercially pure titanium porous coating.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 3 of 45

{3}

Table 1. 36 mm Ceramax® System Component Compatibility

|  Femoral Stem | BIOLOX *delta* femoral head (OD, neck lengths, internal tapers) | Ceramax® ceramic acetabular insert (ID X OD) | Pinnacle® 100 and Sector II acetabular shells (OD) | 6.5mm diameter Pinnacle® Cancellous Bone Screws  |
| --- | --- | --- | --- | --- |
|  **S-ROM® Modular Hip** | **36mm +0, +3, and +6 (11/13 taper)** | **36 x 52, 36x 54, 36x 56, 36x 58, 36x 60, 36x 62, 36x 64, 36x 66mm** | **52 – 66mm** | **15-70mm**  |
|  **Porocoat® Summit™** | **36mm +1.5, +5, +8.5, and +12 (12/14 taper)** | **36 x 52, 36x 54, 36x 56, 36x 58, 36x 60, 36x 62, 36x 64, 36x 66mm** | **52 – 66mm** | **15-70mm**  |

## **VI. ALTERNATIVE PRACTICES AND PROCEDURES**

There are several other alternatives for the correction of noninflammatory degenerative joint disease (NIDJD) of the hip, including:

- The use of other commercially available total hip replacement implants. Other bearing surface alternatives used in total hip replacement include ceramic on ultra-high molecular weight polyethylene (UHMWPE), metal on metal, ceramic on metal and metal on UHMWPE bearing articulations;
- Non-surgical treatment such as reduced activity and/or pain medication; and
- Other surgical treatments that do not involve the use of an implant, such as hip joint fusion.

Each alternative has its own 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**

DePuy Orthopaedics has marketed the Ceramax® Ceramic Total Hip System worldwide since 2003 in the following countries: Australia, Austria, Belgium, China (Hong Kong), Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Korea, Malaysia, Middle East countries, New Zealand, Netherlands, Philippines, Poland, Portugal, Russia, Singapore, Slovakia, Spain, Slovenia, South Africa, Sweden, Switzerland, Thailand, Turkey and the United Kingdom. These devices have not been withdrawn from marketing in any country for reasons of safety and effectiveness.

## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH**

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 4 of 45

{4}

Below is a list of the potential adverse effects (e.g., complications) associated with the use of the DePuy Ceramax® Ceramic Total Hip System.

# Reported Device Related Adverse Effects

The most commonly reported adverse events related to the DePuy Ceramax® Ceramic Total Hip System device are:

1. Trochanteric bursitis
2. Wound problems
3. Musculoskeletal problems
4. Dislocations

# Potential Adverse Effects

The following adverse effects may occur in association with any hip replacement surgery, including the Ceramax® Ceramic Total Hip System:

- Device failure because the components cannot be expected to indefinitely withstand the activity level and loads of normal healthy bone.
- Surgical complications including, but not limited to: vascular disorders, including thrombus; bronchopulmonary disorders, including emboli; myocardial infarction or death.
- Hematoma or damage to blood vessels resulting in large blood loss.
- Delayed wound healing.
- Superficial or deep infection. Infections may occur months to years after surgery. These infections are difficult to treat and may require reoperation with removal surgery and replacement at a later time.
- Temporary or permanent nerve damage resulting in pain or numbness of the affected limb.
- Metal sensitivity reactions, allergic reactions, or metallosis.
- Possible detachment of the coating(s) on the femoral stem or acetabular shell components, potentially leading to increased debris particles;
- Dislocation and subluxation leading to postoperative joint instability (which may be caused by malpositioning of the implants or muscle/fibrous tissue laxity).
- Loosening of hip replacement components can occur. Early mechanical loosening may result from inadequate initial fixation, malalignment, latent infection, premature loading of the prosthesis, or trauma. Late loosening may result from trauma, infection, biological complications (including osteolysis), or mechanical problems, with the subsequent possibility of bone erosion and/or pain.
- Limb length discrepancy.
- Traumatic arthrosis of the hip from intraoperative positioning of the extremity.
- Device related noise such as, clicking, popping, squeaking or grinding.
- Increased hip pain and/or reduced hip function.
- Fatigue fracture of the implants as a result of excessive loading, malalignment, or trauma.
- Osteolysis and/or other peri-prosthetic bone loss.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 5 of 45

{5}

- Bone perforation or fracture (occurring either intra-operatively or occurring post-operatively as a result of trauma, excessive loading, osteolysis or osteoporosis).
- Periarticular calcification or ossification.
- Wear and deformation of the articular surface (as a result of excessive loading or implant malalignment).
- Inadequate range of motion due to improper selection or positioning of components, by femoral impingement, and periarticular calcification; and
- Death.

Any of these adverse effects may require medical or surgical intervention. In rare cases, these adverse effects may lead to death.

For the specific adverse events that occurred in the clinical studies, please see Section X below.

### IX. SUMMARY OF PRECLINICAL STUDIES

A battery of preclinical laboratory tests were conducted on the alumina composite matrix ceramic material used to manufacture the ceramic components. The metal components that comprise the rest of this system are made from materials that have been used for many years in total hip replacement (THR) surgery.

Non clinical laboratory testing was provided in support of the Ceramax® Ceramic Total Hip System including the information regarding:

- Femoral Head Testing: burst strength, fatigue strength, post-fatigue burst strength, axial pull-off strength
- Acetabular Liner Testing: burst strength, fatigue strength, post-fatigue burst strength, push-out strength, torsional strength, lever-out strength
- Bearing Couple: range of motion, wear
- Surface Coating Characterization

A. Laboratory Studies

|  Test | Purpose/Methods | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|  Ceramic Head Static Burst Testing | Static burst or 'crush' testing was performed to evaluate the ability of the individual ceramic head components and the system as a whole to withstand static axial compression. Static burst testing of Biolox delta ceramic ball heads used for the DePuy Ceramax® Ceramic Total Hip System was conducted. Twelve | The Ceramic Ball guidance document suggests a minimum average burst strength of 46kN with no individual failure below 20 kN, so the construct tested met the acceptance | The average load to fracture for the 36-11/13 (+12 mm) heads was 105 kN, with no head fracturing below 68kN. The average load to fracture for the 36-12/14 (+12 mm) heads was 58 kN, with no head fracturing below 46kN.  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 6 of 45

{6}

|  Test | Purpose/Methods | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | tests were performed using 36-11/13 (+12 mm) Biolox delta ceramic ball heads on trunnions from DePuy stems representing the worst case combination. Seven tests were performed using 36-12/14 (+12 mm) Biolox delta ceramic ball heads on trunnions from DePuy stems representing the worst case combination. | criteria. |   |
|  Ceramic Head Fatigue Testing | Fatigue testing of three 36-11/13 (+12 mm) Biolox delta ceramic ball heads on DePuy stem tapers and three 36-12/14 (+12 mm) Biolox delta ceramic ball heads on DePuy stem tapers was conducted. The applied load was cycled to 14.0 to 0.5kN at a frequency of 10 Hz in Ringers solution at ambient temperature. | No cracks or ball fracture after 10 million cycles. | All specimens reached 10 million cycles without failure or formation of macroscopically detectable defects.  |
|  Post-Fatigue Burst Testing | Following fatigue testing, Burst testing of the three 36-11/13 (+12 mm) samples and three 36-12/14 (+12 mm) samples was performed. | Greater than 20kN as required for the post-fatigue burst strength suggested by the FDA Ceramic Ball Guidance.^{1} | The 36-11/13 samples had an average burst test value of 78 kN and a minimum value of 67 kN. The 36-12/14 samples had an average burst test value of 65 kN and a minimum value of 52 kN.  |
|  Ceramic Head Axial Pull-off Testing | Five 36-11/13 (+12 mm) and five 36-12/14 (+12 mm) Biolox delta ceramic ball heads were tested for pull-off loads using DePuy stem trunnions. | No universal acceptance criteria. Compared to in-vivo conditions | The average pull-off load for the 36-11/13 (+12 mm) samples was 1309 N. The average pull-off load for the 36-12/14 (+12 mm) samples was 1094 N.  |
|  Ceramic Liner Burst Test | The purpose of this test was to determine the minimum burst | An average burst strength greater | The mean static axial compressive fracture  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 7 of 45

{7}

|  Test | Purpose/Methods | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | strength (static axial compression fracture load) for the smallest ceramic liners. Seven worst case 36/52 mm ceramic liner/52 mm acetabular metal shell assemblies were static burst tested using 36mm Biolox delta (zirconia composite) ceramic heads. | than 46 kN with no single sample below 25 kN. | load for the DePuy 36 millimeter ceramic insert was > 285 kN with no values below 285 kN. All inserts were loaded up to the machine capacity without failing.  |
|  Ceramic Liner Fatigue/Post-Fatigue Burst Test | The purpose of this test was to determine the minimum burst strength for the worst case liner assembly after cyclic fatigue testing. Three worst case 36/52 mm ceramic liner/52 mm acetabular metal shell assemblies were fatigue tested in axial compression using an applied load cycled from 14.0 kN to 0.5 kN at a frequency of 10 Hz in Ringers solution at ambient temperature for 20 million cycles. | The acceptance criteria required the ceramic liner samples to pass 20 million cycles at 14kN with no macroscopically visible component failure and have no post-fatigue burst strength below 25 kN. | No failures or fractures occurred. The mean post fatigue burst strength for the DePuy 36 mm ceramic insert was 290 kN with no values below 290 kN. All inserts were loaded up to the machine capacity without failing.  |
|  Ceramic Liner Push-out Testing | The purpose of this push-out testing was to evaluate the integrity of the liner/shell connection (i.e., locking mechanism) of the acetabular system. Five worst case 36/52 mm ceramic liner/52 mm acetabular metal shells underwent push-out testing. | The acceptance criterion required an average push-out value greater than 200 N. | The mean pre-fatigue push-out force for the 36/52 mm liner/52 mm shell was 1595 N with no values below 1550 N  |
|  Acetabular Liner Rotational Stability (Torsional Test) | The purpose of this torsional test was to evaluate the integrity of the liner/shell connection (i.e., locking mechanism) of the acetabular system by determining the torsional force required to dissociate the taper-fit between a ceramic liner and an acetabular shell. Three worst case 36/52 mm ceramic liner/52 | The acceptance criterion was defined as an average torsional force greater than 4 N*m (400 N*cm). | The mean rotational moment (torque) of the 36mm acetabular construct was 3408 N*cm with no values below 760 N*cm.  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 8 of 45

{8}

|  Test | Purpose/Methods | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | mm acetabular metal shells underwent torsional testing. The 36/52 mm liner/52 mm metal shell assembly was determined to be the worst case for the testing because it has the least amount of taper surface contact area within the DePuy implant system under consideration. |  |   |
|  Acetabular Liner Lever-Out Test | The purpose of this test was to evaluate the integrity of the liner/shell connection (i.e., locking mechanism) of the acetabular system by determining the lever-out force required to dissociate the taper-fit between a ceramic liner and an acetabular shell. Three worst case 36/52 mm ceramic liner/52 mm acetabular metal shells underwent lever-out testing. The 36/52 mm liner/52 mm metal shell assembly was determined to be the worst case for the testing because it has the least amount of taper surface contact area within the DePuy implant system under consideration. | The acceptance criteria was defined as an average lever-out strength greater than 3000 N*cm. | The mean lever-out force of the 36 mm acetabular construct was 10,199 N*cm with no values below 9443 N*cm.  |
|  Range of Motion, Head/Liner Constraint | A computer aided design (CAD) range of motion (ROM) analysis of the total hip construct was performed to measure the constraint of the DePuy Ceramax® Ceramic Total Hip System with the S-ROM® femoral stems. ROM measurements in the anterior/posterior (A/P) and medial/lateral (M/L) directions were made for each DePuy femoral stem, femoral head and acetabular cup combination | The acceptance criterion was defined as ROM > 112° in the anterior/posterior direction | The 36mm combination yielded 148° minimum ROM in the anterior/posterior direction. The minimum ROM in the medial/lateral direction was determined to be 142°.  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 9 of 45

{9}

|  Test | Purpose/Methods | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | representing worst case scenarios to establish the worst case (minimum) ROM values. The worst case (least ROM) combination of 36mm implants was determined to be the 36 mm x 54 mm ceramic insert with the S-ROM® (11/13 taper) femoral stems. |  |   |
|  Wear of Alumina Composite Matrix Ceramic-on-Ceramic Hip Bearings | The purpose of this test was to assess the amount of wear debris produced from the ceramic-on-ceramic articulation. A wear test was designed to replicate an in vivo condition, comparing the amount of wear debris produced by the 36 mm (36/62 mm acetabular shell) ceramic-on-ceramic couple (n=3) against a control group with 36 mm (36/52 mm acetabular shell) metal-on-metal couple (n=2). The motion was flexion/extension of +30/-15°, internal/external rotation of +10/-10°. The components were subjected to a repetitive Paul type stance phase loading (ISO 14242-1) with a maximum load of 3kN and swing phase load minimum of 300N. The lubricant used was 25% new born calf serum (75% v/v deionized water) with sodium azide and EDTA additions. The lubricant was changed regularly throughout the test at intervals of approximately 300,000 cycles. The wear was assessed gravimetrically at intervals of 0.5 million cycles from 0 to 2 million and thereafter every 1 | The acceptance criterion for this wear test was lower volumetric wear generated by the 36 mm Biolox delta ceramic-on-ceramic couple than for a 36 mm metal-on-metal couple. | There was no measurable difference in diameter of the component before or after the test. The total wear at 6 million cycles was measured as 1.72 mm3 for 36mm metal-on- metal and -0.108 mm3 for 36mm ceramic-on-ceramic. However, the measurement conditions were not accurate enough to measure the small weight changes experienced during simulation as wear rates were very low when articulating with Biolox delta ceramic.  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 10 of 45

{10}

|  Test | Purpose/Methods | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | million cycles up to a maximum of 6 million cycles. |  |   |
|  Surface Coating Characterization | The purpose of this testing was to characterize the femoral stem and acetabular shell porous-surface coatings with regard to coating thickness, bead morphology, pore size, porosity, and bond strength characteristics in accordance with the FDA Orthopedic Device Coating Guidance.^{2} | In accordance with the guidance and standards | The S-ROM® femoral stem commercially pure (CP) titanium coating has: a mean coating thickness of 229 μm; a spherical bead shape; a mean pore diameter of 125 μm; a mean volume percent porosity of 34%; a mean shear strength of 46.1 MPa; and, a mean tensile pull-off strength of 70.0 MPa. The Porocoat® Summit™ femoral stem and Pinnacle® acetabular cup porous coating has; a mean coating thickness of 762 μm; a spherical bead shape; a mean pore diameter of 275 μm; a mean volume percent porosity of 51%; a mean shear strength of 25.5 MPa; and, a mean tensile pull-off strength of 21.1 MPa.  |

### B. Animal Studies

No animal studies have been performed. Animal studies were not deemed necessary to determine the safety and effectiveness of the DePuy Ceramax® Ceramic Total Hip System.

### C. Additional Studies

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 11 of 45

{11}

# Biocompatibility

The materials for use in the Ceramax® Ceramic Total Hip System are standard materials used in permanently, implanted orthopaedic implants, including titanium alloy (ASTM F136, ASTM F620) and Biolox delta ceramic.

# Sterilization

DePuy ceramic femoral heads and ceramic liners are sterilized by gamma radiation sterilization (Cobalt 60 Source) at a dose of 25kGy (2.5Mrad). The process is validated per the requirements of ISO 1113734³ to yield a minimum Sterility Assurance Level (SAL) of 10⁻⁶. The product is not labeled "pyrogen free". The components are packaged in Tyvek/PETG trays to maintain sterility.

# Shelf-Life

Shelf life testing was performed to verify sterile packaging integrity equivalent to 11 years for the Ceramax® Ceramic Total Hip System.

# X. SUMMARY OF PRIMARY CLINICAL STUDIES

The applicant performed a two-armed clinical study to establish a reasonable assurance of safety and effectiveness of total hip arthroplasty with the DePuy Ceramax® Ceramic Total Hip System for non-inflammatory degenerative joint disease in the US under IDE #G030075. One study arm investigated the 28mm sizes of ceramic components and the second arm the 36mm ceramic components. Please see the original SSED for details on 28mm ceramic clinical study arm. Data from the 36mm clinical study, along with a post hoc subgroup analysis of only the subset of components the applicant is proposing to market (DePuy S-ROM® femoral stems, Porocoat® Summit™ femoral stems, DePuy Pinnacle® 100 and Pinnacle® Sector II acetabular cups), were the basis for the PMA approval decision. A summary of the 36mm clinical study is presented below.

# A. 36MM Study Design

Patients were treated between April 12, 2006 and August 29, 2007. The database for this PMA reflected data collected from April 2006 to March 2011 and included 264 patients. The first surgery occurred on October 28, 2003 and the last surgery on December 28, 2005. There were five investigational sites and 11 surgeons.

The study was a prospective, multi-center, nonrandomized, controlled clinical study of the 36mm ceramic-on-ceramic hip components of the DePuy Ceramax® Ceramic Total Hip System (COC36) compared to a conventional 28mm ceramic-on -polyethylene articulation hip system (COP28).

The investigational group (n=168 subjects) received commercially-available cementless porous coated acetabular cup prosthesis (Pinnacle®™) and an investigational ceramic

3 Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization using AAMI TIR27 Sterilization of health care products – Radiation sterilization – substantiation of 25kGy as a sterilization dose – Method VDmax

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 12 of 45

{12}

bearing insert (Ceramax®) with a 36mm inner diameter. The control group (n=74 subjects) received commercially-available cementless porous-coated acetabular cup prosthesis (Pinnacle®™) and a commercially-available polyethylene bearing insert (Marathon™) with a 28mm inner diameter. Both treatments received a commercially available femoral stem. The control group was an active treatment with a legally marketed alternative with similar indications for use.

Femoral stem components used in this investigation consisted of implantations with Porocoat® Summit™, Summit™ Duofix, S-ROM®, Prodigy™, AML, and Corail™ hip stems. Pinnacle® 100, Pinnacle® 300 and Pinnacle® Sector II acetabular cups were used. Commercially available 28mm and 36mm Biolox® ceramic femoral heads were used on all femoral stems. In PMA P070026, the applicant is only seeking marketing approval for the following subset of the 36mm Ceramax® components studied in the IDE: S-ROM® femoral stems, Porocoat® Summit™ stems, Pinnacle® 100 and Pinnacle® Sector II acetabular cups.

# 1. Clinical Inclusion and Exclusion Criteria

Enrollment in the DePuy Ceramax® Ceramic Total Hip System investigational study was limited to patients who met the following inclusion criteria:

- Cementless total hip replacement in skeletally mature (tibial and femoral epiphyses are closed) individuals 20 to 75 years of age at the time of surgery undergoing primary hip surgery for noninflammatory degenerative joint disease (NIDJD)
- Composite diagnoses of NIDJD include osteoarthritis, avascular necrosis, posttraumatic arthritis, slipped capital femoral epiphysis (SCFE), fracture of the pelvis, and developmental dysplasia
- Patients with a previous total hip replacement of the contralateral leg that has a pain rating of none or slight and who are at least one year post arthroplasty are eligible for participation in the study
- Preoperative Harris Hip Total score of less than or equal to 70
- Preoperative Harris Hip Total Pain score at least Moderate
- Radiographic evaluation confirms the presence of NIDJD
- Radiographic evaluation confirms that there is sufficient femoral and acetabular bone stock, regarding strength and shape, and is suitable to receive the implants

Patients were not permitted to enroll in the DePuy Ceramax® Ceramic Total Hip System investigational study if they met any of the following exclusion criteria:

- Presence of a previous prosthetic hip replacement device (any type, including surface replacement arthroplasty, endoprosthesis, etc.) in the hip joint to be operated
- Previous Girdlestone procedure (resection arthroplasty) or surgical fusion of the hip to be operated
- Acute femoral neck fracture
- Above knee amputation of the contralateral and/or ipsilateral leg

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 13 of 45

{13}

- Patients with bilateral degenerative joint disease requiring staged or simultaneous hip replacements

- Patients with an existing total hip arthroplasty in the contralateral hip with a Harris Hip pain rating of mild, moderate marked or totally disabled

- Patients who have undergone total hip arthroplasties in their contralateral hips within the past 12 months

- Patients with a known allergy to metal (e.g., jewelry)

- Skeletally immature patients (tibial and femoral epiphyses are not closed)

- Evidence of active infections that may spread to other areas of the body (e.g., osteomyelitis, pyogenic infection of the hip joint, overt infection, urinary tract infection, etc.)

- The presence of highly communicable disease or diseases that may limit followup (e.g., immuno-compromised conditions, hepatitis, active tuberculosis, etc.)

- Presence of known metastatic or neoplastic disease

- Significant neurologic or musculoskeletal disorders or disease that may adversely affect gait or weight bearing, (e.g., muscular dystrophy, multiple sclerosis)

- Conditions that may interfere with the total hip arthroplasty's survival or outcome, (e.g., Paget's disease, Charcot's disease)

- Any patient believed to be unwilling or unable to comply with a rehabilitation program for a cementless total hip replacement or who indicates difficulty or inability to return for follow-up visits prescribed by the study protocol

- Patient is known to be pregnant, a prisoner, mentally incompetent, and/or alcohol or drug abuser

- Any systemic steroid therapy, excluding inhalers, within three months prior to surgery

- Patients carrying the diagnosis of inflammatory degenerative arthritis (IDJD) to include the following composite diagnoses: rheumatoid arthritis, systemic lupus erythematosus, pigmented villonodular synovitis, juvenile rheumatoid arthritis and other arthritic processes of inflammatory or autoimmune etiology

- Patients requiring structural bone grafts in order to support the prosthetic component(s) or to shape the bone to receive the implant(s)

- Patients who refuse to provide consent to participate in the clinical investigation

- Surgical replacement requires the use of an acetabular liner and femoral head greater or smaller than a 36mm diameter.

# 2. Follow-up Schedule

All patients were scheduled to return for follow up examination at 6-weeks, 6-months, 12-months, 24-months and then annually following their surgeries.

(Table 1) In addition, beginning at 12-months postoperatively patient-reported satisfaction outcomes were collected.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 14 of 45

{14}

Table 1: Protocol Interval Windows

|  Interval | Days  |
| --- | --- |
|  6 weeks = 6 weeks ± 2 weeks | 28 – 60  |
|  6 months = 6 months ± 4 weeks | 150 – 210  |
|  12 months = 12 months ± 8 weeks | 300 – 420  |
|  2 years = 24 months ± 12 weeks | 630 – 810  |
|  3 years* = 36 months ± 16 weeks | 960 – 1200  |
|  4 years* = 48 months ± 20 weeks | 1290 – 1590  |
|  * After 2-year follow-up, subjects continue to be evaluated clinically and radiographically on an annual basis until all available study subjects have achieved a minimum 2-year follow-up.  |   |
|  An Interim Visit Evaluation was completed any time a subject was seen outside of the defined evaluations.  |   |

Preoperatively, all subjects were clinically evaluated by the following: medical history and physical examination, Harris Hip Score (HHS), and subject-reported visual analog scale (VAS) to assess pain.

Postoperatively, all subjects were clinically evaluated at each interval by objective parameters to measure the clinical effectiveness of the device. Clinical effectiveness of this device was measured by Harris Hip Score, VAS pain scale, subjective self report questionnaire, and independently reviewed radiographs. Adverse events and complications were recorded at all visits. (Table 2)

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 15 of 45

{15}

Table 2: Study Evaluation Tools

|  Evaluation Tool | Details | Interval  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  | Preop | Oper-ative | 6 W | 6M | 12M | 24M  |
|  Medical History | Collects subject contact information, demographics, preoperative medical history including concomitant medical conditions, medications, and allergies. This information provided baseline data. | X |  |  |  |  |   |
|  Harris Hip Score | Hips were evaluated using the modified Harris Hip Score to allow an assessment of pain, function, activities, deformity and range of motion. Range of motion was measured with a goniometer. Range of motion was not collected at the 6-week interval to protect against dislocation in the immediate postoperative period. | X |  | X | X | X | X  |
|  VAS Pain Scale | Subjects self-reported their pain at each interval using a 100mm visual analog scale (VAS) in which 0 indicated “No Pain” and 100 indicated “Severe Pain”. The subjects placed a mark on the scale to indicate their level of pain. | X |  | X | X | X | X  |
|  Operative Detail | Information regarding the devices used, surgical technique, intraoperative complications and hip randomization were recorded. |  | X |  |  |  |   |
|  Subject Self-Reported Data | Subjects self-reported their satisfaction (on a CRF) with hip function. |  |  |  |  | X | X  |
|  Radio-graphic Data | No radiographic data were collected preoperatively. Three radiographic views (anteroposterior pelvis, anteroposterior femur and lateral femur) were collected postoperatively. An independent radiographic reviewer reviewed the images to assess radiographic outcomes. The independent radiographic reviewer reviewed the acetabular component position, cup migration, polyethylene liner wear, and bone-implant interface at all intervals. |  |  | X | X | X | X  |
|  Adverse Events | Postoperatively, all adverse events, device-related or not, were collected. |  |  | X | X | X | X  |
|  Interim Visits | Interim Visits were documented and included the reason for the visit. These visits included the spectrum from routine postoperative visits to visits where a subject was evaluated and/or treated for adverse events. |  |  | X | X | X | X  |

The key timepoints are shown above in Tables 1 and 2 summarizing safety and effectiveness.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 16 of 45

{16}

3. Clinical Endpoints

Per the protocol, all subjects were to be evaluated at the 24 Month (or longer) endpoint.

With regard to safety, the following data were collected on all subjects: revisions, adverse events, and survivorship.

With regard to effectiveness, the following data were collected on all subjects:

- Primary Outcomes: Harris Hip Scores, Radiographic Outcomes; Secondary Outcomes: Harris Hip Score Longitudinal Analysis, and Visual Analog Scale scores for pain (VAS).

With regard to success/failure criteria, the primary endpoint of the study was determined at 24 Month (or longer) based upon a comparison of Harris Hip mean scores between the investigational and control group with a 5 point non-inferiority margin. A subject was considered to be a success if all of the following criteria were met at the 24 Month (or longer) endpoint.

Clinical Criteria for Success:

- Harris Hip total score ≥ 80 points.

Radiographic Criteria for Success:

- No radiolucencies greater than 2 mm in any zone.
- No acetabular cup migration greater than 4 mm.
- No change in inclination greater than 40 degrees.
- No osteolysis.

Revision Criteria for Success: No component removal. In addition, any subject that underwent a reoperation where any device component (acetabular or femoral components) was removed or replaced was considered a revision; and classified as a failure.

**B. Accountability of 36MM PMA Cohort**

**36mm All Enrolled Cohort**

At the time of database lock for the 36mm PMA cohort study, 90% (150/167) of the investigational subjects and 96% (68/71) of the control subjects had radiographs, a scorable (complete) Harris Hip CRF and a complete radiographic CRF at the completion of the study, the 24-month or later postoperative visit, for the evaluation of the safety and effectiveness of this device. This is summarized in **Table 3** below.

**Table 3: Subject Accounting for the 36mm All Enrolled Cohort**

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 17 of 45

{17}

|  IDE Study Cohort | Pre-Op |   | 6 Week |   | 6 Month |   | 12 Month |   | 24 Month |   | 24 Month+  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  I | C | I | C | I | C | I | C | I | C | I | C  |
|  Theoretical Due | 168 | 74 | 168 | 74 | 168 | 74 | 168 | 74 | 168 | 74 | 168 | 74  |
|  Expected Due | 168 | 74 | 168 | 73 | 168 | 72 | 168 | 72 | 167 | 71 | 167 | 71  |
|  Withdrawn: Deaths (Cumulative) | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1  |
|  Withdrawn: Components Removed/Revised (Cumulative) | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 2 | 3 | 2  |
|  Withdrawn: Consent (Cumulative) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1  |
|  Actual | 168 | 74 | 163 | 69 | 141 | 65 | 151 | 67 | 131 | 61 | 150 | 68  |
|  %Follow-up = Actual / Expected Due | 100% | 100% | 97% | 95% | 84% | 90% | 90% | 93% | 78% | 86% | 90% | 96%  |

Theoretical Due: The number of implants that have entered the beginning of each interval window at the time of database lock.

Expected Due: Theoretical due subjects with complete follow-up minus study withdrawals for death or revision.

% Follow-up: % of hips with radiographs, a scorable (complete) Harris Hip CRF and a complete radiographic CRF.

Withdrawn: Consent (Cumulative): does not include subjects who withdrew consent after complete 24 Month+ data had been obtained.

Figure 1 below is a dataset flowchart which shows all COC36 and COP28 enrolled subjects, how the 242 patients in the 36mm Study Safety Dataset were obtained, and the order in which they were excluded, from top to bottom, to obtain the 24+ Month Efficacy and the 24+ Month Success/Failure datasets; revisions were retained for composite success analysis regardless of exclusion criteria. The primary endpoint non-inferiority test of 24+ Month HH mean scores was carried out on the 24+ Month Efficacy Dataset.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 18 of 45

{18}

Figure 1: Patient Accounting Dataset Flowchart: 36mm All Enrolled Cohort

![img-0.jpeg](img-0.jpeg)

### Subset Cohort of 36mm Study Patients with S-ROM® and Summit™ Porocoat® Femoral Stems and Pinnacle® 100 (Porocoat®) and Sector II (Porocoat®) Acetabular Cups

The primary analysis was based on six femoral stem types and two acetabular cup types. Marketing approval was sought for the S-ROM® and Summit™ Porocoat® femoral stems and Pinnacle® 100 (Porocoat®) and Sector II (Porocoat®) acetabular cups as components for the 36mm DePuy Ceramax® Ceramic Total Hip System. At the time of database lock, 89 investigational and 38 control subjects in the 36mm Subset Cohort of subjects with these components had a scorable (complete) Harris Hip CRF and a complete radiographic CRF at the 24-month or later postoperative visit. This is summarized in Table 4 below.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 19 of 45

{19}

Table 4: Subject Accounting for the 36mm Subset Cohort

|  36mm Subset Cohort | Pre-Op |   | 6 Week |   | 6 Month |   | 12 Month |   | 24 Month |   | 24 Month+  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  I | C | I | C | I | C | I | C | I | C | I | C  |
|  Theoretical Due | 98 | 40 | 98 | 40 | 98 | 40 | 98 | 40 | 98 | 40 | 98 | 40  |
|  Expected Due | 98 | 40 | 98 | 39 | 98 | 39 | 98 | 39 | 98 | 38 | 98 | 38  |
|  Withdrawn: Deaths (Cumulative) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0  |
|  Withdrawn: Components Removed/Revised (Cumulative) | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 1 | 2  |
|  Withdrawn: Consent (Cumulative) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0  |
|  Actual | 98 | 40 | 94 | 37 | 83 | 36 | 87 | 37 | 77 | 32 | 89 | 38  |
|  %Follow-up = Actual / Expected Due | 100% | 100% | 96% | 95% | 85% | 92% | 89% | 95% | 79% | 84% | 91% | 100%  |

Theoretical Due: The number of implants that have entered the beginning of each interval window at the time of database lock.

Expected Due: Theoretical due subjects with complete follow-up minus study withdrawals for death or revision.

% Follow-up: % of hips with radiographs, a scorable (complete) Harris Hip CRF and a complete radiographic CRF.

Withdrawn: Consent (Cumulative): does not include subjects who withdrew consent after complete 24 Month+ data had been obtained.

Figure 2 below is a dataset flowchart which shows all 138 36mm Study subjects with S-ROM® and Summit™ Porocoat® Femoral Stems and Pinnacle® 100 (Porocoat®) and Sector II (Porocoat®) Acetabular Cups in the Safety Dataset, and the order in which they were excluded, from top to bottom, in order to obtain the 36mm Subset Cohort of subjects in the Efficacy Dataset and in the Success/Failure Dataset; revisions were retained for composite success, regardless of exclusion criteria.

Figure 2: Study Subject Accounting Dataset Flowchart: 36mm Subset Cohort

![img-1.jpeg](img-1.jpeg)

### C. 36mm PMA Study Population Demographics and Baseline Parameters

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 20 of 45

{20}

The demographics of the 36mm PMA Study population are typical for a total hip replacement study performed in the U.S. Clinical study data was collected on 242 hips implanted. There were 168 investigational hip implantations and 74 control hip implantations in the 36mm Protocol Defined Safety Dataset for the 36mm All Enrolled Cohort.

Comparisons were performed to determine whether the subject populations for the treatment groups were equivalent prior to study treatment. Comparisons were conducted using the 36mm Safety Dataset: means were compared with a t-test, and proportions were compared with Fisher’s exact test. Results of these analyses are provided in **Table 5** below.

**Table 5: Study Baseline Demographics for the 36mm Safety Dataset**

|  Demographic Element |  | Investigational N=168 | Control N=74 | Investigational vs. Control p-values  |
| --- | --- | --- | --- | --- |
|  Enrollment | Number of procedures | 168 | 74 | -  |
|   |  Number of patients | 168 | 74 | -  |
|  Age in years | Mean Age | 57.3 | 56.9 | 0.781  |
|   |  Minimum Age | 24 | 29  |   |
|   |  Maximum Age | 75 | 74  |   |
|  Gender | Females | 76 (45%) | 27 (36%) | 0.259  |
|   |  Males | 92 (55%) | 47 (64%)  |   |
|  Body Mass Index [kg / m^{2}] | Mean BMI | 29.0 | 29.9 | 0.318  |
|   |  Minimum BMI | 18.4 | 18.8  |   |
|   |  Maximum BMI | 51.1 | 47.1  |   |
|  Primary Diagnosis | Avascular Necrosis | 13 (8%) | 4 (5%) | 0.597  |
|   |  Developmental Dysplasia | 3 (2%) | 1 (1%) | 1.000  |
|   |  Epiphyseal Defect | 2 (1%) | 2 (3%) | 0.588  |
|   |  Osteoarthritis | 148 (88%) | 65 (88%) | 1.000  |
|   |  Post Traumatic Arthritis | 2 (1%) | 2 (3%) | 0.588  |
|  Harris Hip Score | Mean Pre-Op HH Score | 52.9 | 52.1 | 0.564  |
|   |  Minimum Pre-Op HH Score | 18.0 | 26.0  |   |
|   |  Maximum Pre-Op HH Score | 70.0 | 76.0  |   |
|  Harris Hip Pain Category (Range 0-44) | Mean Pre-op HH Pain | 14.9 | 14.1 | 0.252  |
|   |  Minimum Pre-op HH Pain | 0.0 | 10.0  |   |
|   |  Maximum Pre-op HH Pain | 20.0 | 30.0  |   |
|  Harris Hip Function Score (Range 0-33) | Mean Pre-op HH Function | 20.9 | 20.6 | 0.702  |
|   |  Minimum Pre-op HH Function | 2.0 | 5.0  |   |
|   |  Maximum Pre-op HH Function | 30.0 | 30.0  |   |
|  Harris Hip Activity Score (Range 0-14) | Mean Pre-op HH Activity | 8.6 | 8.9 | 0.373  |
|   |  Minimum Pre-op HH Activity | 0.0 | 1.0  |   |
|   |  Maximum Pre-op HH Activity | 14.0 | 14.0  |   |
|  Harris Hip | Mean Pre-op HH Deformity | 3.9 | 3.7 | 0.332  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 21 of 45

{21}

|  Demographic Element |  | Investigational N=168 | Control N=74 | Investigational vs. Control p-values  |
| --- | --- | --- | --- | --- |
|  Deformity Score (Range 0-4) | Minimum Pre-op HH Deformity | 0.0 | 0.0 |   |
|   |  Maximum Pre-op HH Deformity | 4.0 | 4.0  |   |
|  Harris Hip Range of Motion Score (Range 0-5) | Mean Pre-op HH ROM | 4.6 | 4.6 | 0.652  |
|   |  Minimum Pre-op HH ROM | 0.0 | 3.4  |   |
|   |  Maximum Pre-op HH ROM | 5.0 | 5.0  |   |

The demographics of the 36mm Subset Cohort (subjects who received S-ROM® and Summit™ Porocoat® Femoral Stems and Pinnacle® 100 and Sector II Acetabular Cups) study population are typical for a total hip replacement study performed in the U.S. and consistent with the demographics of the 36mm All Enrolled cohort.

Comparisons were performed to determine whether the patient populations for the treatment groups were equivalent prior to study treatment. Comparisons were conducted using the subset of subjects from the 36mm Safety Dataset with S-ROM® and Porocoat® Summit™ femoral stems and Pinnacle® 100 and Pinnacle® Sector II acetabular cups: means were compared with a t-test, and proportions were compared with Fisher's exact test. Results of these analyses are provided in Table 6 below.

Table 6: Baseline Demographics for the 36mm Subset Cohort of Safety Dataset Subjects

|  Demographic Element |  | Investigational N=98 | Control N=40 | Investigational vs. Control p-values  |
| --- | --- | --- | --- | --- |
|  Enrollment | Number of procedures | 98 | 40 | -  |
|   |  Number of patients | 98 | 40 | -  |
|  Age in years | Mean Age | 58.1 | 58.5 | 0.849  |
|   |  Minimum Age | 32 | 39  |   |
|   |  Maximum Age | 75 | 74  |   |
|  Gender | Females | 32 (33%) | 13 (33%) | 1.000  |
|   |  Males | 66 (67%) | 27 (68%)  |   |
|  Body Mass Index [kg / m²] | Mean BMI | 29.3 | 30.3 | 0.406  |
|   |  Minimum BMI | 18.4 | 18.8  |   |
|   |  Maximum BMI | 49.5 | 45.9  |   |
|  Primary Diagnosis | Avascular Necrosis | 4 (4%) | 0 (0%) | 0.323  |
|   |  Developmental Dysplasia | 0 (0%) | 0 (0%) | 1.000  |
|   |  Epiphyseal Defect | 0 (0%) | 0 (0%) | 1.000  |
|   |  Osteoarthritis | 93 (95%) | 40 (100%) | 0.321  |
|   |  Post Traumatic Arthritis | 1 (1%) | 0 (0%) | 1.000  |
|  Harris Hip Score | Mean Pre-Op HH Score | 51.6 | 49.7 | 0.347  |
|   |  Minimum Pre-Op HH Score | 18.0 | 26.0  |   |
|   |  Maximum Pre-Op HH Score | 70.0 | 68.0  |   |
|  Harris Hip | Mean Pre-op HH Pain | 14.2 | 13.2 | 0.211  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 22 of 45

{22}

|  Demographic Element |  | Investigational N=98 | Control N=40 | Investigational vs. Control p-values  |
| --- | --- | --- | --- | --- |
|  Pain Category (Range 0-44) | Minimum Pre-op HH Pain | 0.0 | 10.0 |   |
|   |  Maximum Pre-op HH Pain | 20.0 | 20.0  |   |
|  Harris Hip Function Score (Range 0-33) | Mean Pre-op HH Function | 20.4 | 19.7 | 0.436  |
|   |  Minimum Pre-op HH Function | 2.0 | 5.0  |   |
|   |  Maximum Pre-op HH Function | 30.0 | 27.0  |   |
|  Harris Hip Activity Score (Range 0-14) | Mean Pre-op HH Activity | 8.5 | 8.7 | 0.735  |
|   |  Minimum Pre-op HH Activity | 2.0 | 2.0  |   |
|   |  Maximum Pre-op HH Activity | 14.0 | 14.0  |   |
|  Harris Hip Deformity Score (Range 0-4) | Mean Pre-op HH Deformity | 3.7 | 3.6 | 0.429  |
|   |  Minimum Pre-op HH Deformity | 0.0 | 0.0  |   |
|   |  Maximum Pre-op HH Deformity | 4.0 | 4.0  |   |
|  Harris Hip Range of Motion Score (Range 0-5) | Mean Pre-op HH ROM | 4.6 | 3.7 | 0.555  |
|   |  Minimum Pre-op HH ROM | 0.9 | 3.8  |   |
|   |  Maximum Pre-op HH ROM | 5.0 | 5.0  |   |

### D. 36mm Study Safety and Efficacy Results

#### 1. Safety Results

The analysis of safety was based on the following:

- Adverse Events
- Kaplan-Meier survivorship analysis of revisions

The analysis of safety was based on all 242 enrolled subjects (168 investigational and 74 control cohorts) followed over the 24+ Month evaluation.

The key safety outcomes for this study are presented below in Tables 5 through 20.

Adverse events that occurred in the 36mm PMA clinical study:

The Safety Dataset was used to compare:

1) Revisions,
2) Intraoperative complications,
3) Postoperative, systemic adverse events and
4) Postoperative, operative site adverse events

between investigational and control treatment groups.

#### a. Adverse Events

1. Revisions

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 23 of 45

{23}

Revision was defined as a reoperation where any component (acetabular or femoral) was removed or replaced. There were a total of 3 revisions (1.8%) reported out of 168 procedures in the investigational cohort and 2 revisions (2.7%) reported out of 74 procedures in the control cohort at 24+ months. **Table 7** provides a summary of the revision procedure, treatment group, age, gender, and primary diagnosis, duration of implantation and reason for revision for each patient. There appears to be no clinically meaningful difference in rates of revision between the investigational and control treatments.

**Table 7: 36mm PMA Study Investigational and Control Device Revisions**

|  Revision Procedure(s): F = Femoral Stem S = Acetabular Shell H = Femoral Head I = Acetabular Insert | Treatment Group | Age / Gender | Primary Diagnosis | Duration of Implantation | Reason for Revision / Removal  |
| --- | --- | --- | --- | --- | --- |
|  H, I | COC36 | 26/F | Avascular Necrosis | 3.53 yrs | Deep infection  |
|  H, I | COC36 | 59/F | Osteo-arthritis | 1.67 yrs | Ceramic liner fracture observed on radiograph  |
|  1st revision: F, H (0.58 years), Subject not withdrawn from study 2nd revision: S, I (2.92 years) | COC36 | 52/M | Osteo-arthritis | 0.58 yrs | Femoral component loosening (revised at 0.58 years); Acetabular component loosening (revised/withdrawn at 2.92 years)  |
|  H, I | COP28 | 68 / F | Osteoarthritis | 20 months | Recurrent dislocations  |
|  H, I | COP28 | 63 / M | Osteoarthritis | 13 days | Recurrent dislocations  |

### **Kaplan-Meier Survivorship Analysis**

Kaplan-Meier analyses were carried out to determine the expected rate of revision for any reason for both treatment groups. Revision was defined as a reoperation where any component (acetabular or femoral) was removed or replaced. The 'years' variable was calculated using time from surgery to revision for any reason. Subjects not having a revision had their time calculated one of two ways: 1) time from surgery to last clinical or radiographic evaluation, or 2) time from surgery to death. Subjects not having a revision had their time variable censored.

The results are presented graphically in **Figure 3** and in tabular form across time in **Table 8**. When revision was defined as the endpoint for survivorship, the results demonstrated a 97.5 % survivorship (95% confidence interval: 91.9%-99.2%) for the investigational subjects at 4.1 years and a 97.3% survivorship (95% confidence interval:

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 24 of 45

{24}

89.6%-99.3%) for the control hips 5.6 years. There was no clinically or statistically significant difference between investigational and control subjects (log-rank p-value =0.734).

Survivorship analyses for the 36mm Subset Cohort (subjects who received S-ROM® and Summit™ Porocoat® Femoral Stems and Pinnacle® 100 and Sector II Acetabular Cup) are presented graphically in Figure 4 and in tabular form across time in Table 9. Results for the 36mm Subset Cohort demonstrated a 99% survivorship (95% confidence interval: 92.8%-99.9%) for the investigational subjects at 4.1 years and a 95.0% survivorship (95% confidence interval: 81.5%-98.7%) for the control hips at 5.2 years. There was no clinically or statistically significant difference between investigational and control subjects (log-rank p-value =0.153).

Figure 3: Kaplan-Meier Survivorship Estimates: 36mm All Enrolled Cohort

![img-2.jpeg](img-2.jpeg)

Table 8: Safety Dataset - Survival Estimates Across Time 36mm COC Study: 36mm All Enrolled Cohort

|  Treatment |  | 0 | 0.5 | 1 | 1.5 | 2 | 2.5 | 3 | 3.5 | 4 | 4.5 | 5 | 5.5 | 6  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  C | Survival Estimate | 100.0 | 98.6 | 98.6 | 98.6 | 97.3 | 97.3 | 97.3 | 97.3 | 97.3 | 97.3 | 97.3 | 97.3 |   |
|  C | Lower 95% Confidence Limit | 100.0 | 90.8 | 90.8 | 90.8 | 89.6 | 89.6 | 89.6 | 89.6 | 89.6 | 89.6 | 89.6 | 89.6 |   |
|  C | Upper 95% Confidence Limit | 100.0 | 99.8 | 99.8 | 99.8 | 99.3 | 99.3 | 99.3 | 99.3 | 99.3 | 99.3 | 99.3 | 99.3 |   |
|  C | Hips Remaining | 74 | 72 | 72 | 72 | 67 | 65 | 60 | 55 | 53 | 42 | 36 | 21 | <20  |
|  C | Accumulative Hips Revised | 0 | 1 | 1 | 1 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2  |
|  I | Survival Estimate | 100.0 | 100.0 | 99.4 | 99.4 | 98.8 | 98.8 | 98.8 | 98.8 | 97.5 |  |  |  |   |
|  I | Lower 95% Confidence Limit | 100.0 | 100.0 | 95.8 | 95.8 | 95.2 | 95.2 | 95.2 | 95.2 | 91.9 |  |  |  |   |
|  I | Upper 95% Confidence Limit | 100.0 | 100.0 | 99.9 | 99.9 | 99.7 | 99.7 | 99.7 | 99.7 | 99.2 |  |  |  |   |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 25 of 45

{25}

|  Treatment |  | 0 | 0.5 | 1 | 1.5 | 2 | 2.5 | 3 | 3.5 | 4 | 4.5 | 5 | 5.5 | 6  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  I | Hips Remaining | 168 | 166 | 162 | 159 | 152 | 133 | 126 | 78 | 52 | <20 |  |  |   |
|  I | Cumulative Hips Revised | 0 | 0 | 1 | 1 | 2 | 2 | 2 | 2 | 3 | 3 |  |  |   |

Figure 4: Kaplan-Meier Survivorship Estimates: 36mm Subset Cohort

Kaplan-Meier Survivorship
Event=Revision For Any Reason

![img-3.jpeg](img-3.jpeg)

Table 9: Safety Dataset- Survival Estimates Across Time: 36mm Subset Cohort

|  Treatment |  | 0 | 0.5 | 1 | 1.5 | 2 | 2.5 | 3 | 3.5 | 4 | 4.5 | 5 | 5.5  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  C | Survival Estimate | 100.0 | 97.5 | 97.5 | 97.5 | 95.0 | 95.0 | 95.0 | 95.0 | 95.0 | 95.0 | 95.0 |   |
|  C | Lower 95% Confidence Limit | 100.0 | 83.5 | 83.5 | 83.5 | 81.5 | 81.5 | 81.5 | 81.5 | 81.5 | 81.5 | 81.5 |   |
|  C | Upper 95% Confidence Limit | 100.0 | 99.6 | 99.6 | 99.6 | 98.7 | 98.7 | 98.7 | 98.7 | 98.7 | 98.7 | 98.7 |   |
|  C | Hips Remaining | 40 | 39 | 39 | 39 | 37 | 36 | 33 | 32 | 30 | 23 | 20 | <20  |
|  C | Accumulative Hips Revised | 0 | 1 | 1 | 1 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2  |
|  I | Survival Estimate | 100.0 | 100.0 | 99.0 | 99.0 | 99.0 | 99.0 | 99.0 | 99.0 | 99.0 |  |  |   |
|  I | Lower 95% Confidence Limit | 100.0 | 100.0 | 92.8 | 92.8 | 92.8 | 92.8 | 92.8 | 92.8 | 92.8 |  |  |   |
|  I | Upper 95% Confidence Limit | 100.0 | 100.0 | 99.9 | 99.9 | 99.9 | 99.9 | 99.9 | 99.9 | 99.9 |  |  |   |
|  I | Hips Remaining | 98 | 96 | 94 | 94 | 92 | 84 | 78 | 41 | 24 | <20 |  |   |
|  I | Cumulative Hips Revised | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |  |   |

Adverse events reported from the clinical study of 242 hip procedures are listed in Tables 10, 12, 14, 16, 21, and 22 below.

In Tables 10 through 15 below, every unique adverse event was reported once per patient, regardless of whether a single subject reported more than one instance of a particular adverse event.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 26 of 45

{26}

## 2. Intraoperative Complications

The most common intraoperative complication was cardiovascular, which was observed in 1.2% of investigational subjects (2/168). There was no statistically or clinically meaningful difference in the proportions of observed intraoperative adverse events across treatment groups (see Table 8 below). Fisher's exact test was used to compare proportions across the two treatment groups.

Table 10: Comparison of Frequency of Intraoperative Adverse Events: 36mm All Enrolled Cohort

|   | Investigational N=168 |   | Control N=74 |   |   |
| --- | --- | --- | --- | --- | --- |
|  Adverse Events at the 24+ Endpoint | AEs, (%) | 95% Confidence Levels | AEs, (%) | 95% Confidence Levels | p-value  |
|  2cm non-displaced fracture of posterior femoral neck | 1 (0.6%) | 0.0 – 3.3 | 0 (0.0%) | - | 1.000  |
|  Blemish on Ceramic Component | 0 (0.0%) | - | 1 (1.4%) | 0.0 – 7.3 | 0.306  |
|  Broken Drill Bit | 1 (0.6%) | 0.0 – 3.3 | 0 (0.0%) | - | 1.000  |
|  Cardiovascular | 2 (1.2%) | 0.1 – 4.2 | 0 (0.0%) | - | 1.000  |
|  Hematological | 1 (0.6%) | 0.0 – 3.3 | 0 (0.0%) | - | 1.000  |
|  Liner Fracture During Surgery† | 1 (0.6%) | 0.0 – 3.3 | 0 (0.0%) | - | 1.000  |
|  Total† | 6 (3.6%) | 1.3 – 7.6 | 1 (1.4%) | 0.0 – 7.3 | 0.679  |
|  † N=168 investigational subjects + 1 subject who received a metal-on-metal system subsequent to intraoperative ceramic liner fracture.  |   |   |   |   |   |

There were five (5) intraoperative complications among subjects in the 36mm Subset Cohort of subjects with S-ROM® and Porocoat® Summit™ femoral stems and Pinnacle® 100 and Pinnacle® Sector II acetabular cups, as presented in Table 11 below. There appears to be no clinically meaningful difference in rates of intraoperative adverse events between the investigational and control treatments.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 27 of 45

{27}

Table 11: Comparison of Frequency of Intraoperative Adverse Events: 36mm Subset Cohort

|   | Investigational N=98 |   | Control N=40  |   |
| --- | --- | --- | --- | --- |
|  Adverse Events at the 24+ Month Endpoint | AEs, (%) |  | AEs, (%) |   |
|  2cm non-displaced fracture of posterior femoral neck | 1 (1.0%) |  | 0 (0.0%) |   |
|  Broken Drill Bit | 1 (1.0%) |  | 0 (0.0%) |   |
|  Cardiovascular | 2 (2.0%) |  | 0 (0.0%) |   |
|  Hematological | 1 (1.0%) |  | 0 (0.0%) |   |
|  Total | 5 (5.1%) |  | 0 (0.0%) |   |

### 3. 36mm PMA Study Postoperative-Systemic Adverse Events

The most commonly reported postoperative systemic complication reported for investigational subjects was musculoskeletal. Other frequently reported adverse events included: cardiovascular, genitourinary, gastrointestinal, dermatological, and HEENT.

There were no systemic adverse events that occurred with a higher incidence in the 36mm All Enrolled Cohort with statistical significance. The Hematological adverse event rate was significantly higher in the COP28 control group compared to the COC36 investigational group (see Table 12 below).

Table 12: Comparison of Frequency of Postoperative Systemic Adverse Events: 36mm All Enrolled Cohort

|   | Investigational N=168 |   |   | Control N=74 |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Adverse Events at the 24+ Month Endpoint | AEs | % | 95% Confidence Levels | AEs | % | 95% Confidence Levels | p-value  |
|  Cancer | 4 | 2.4 | 0.6 - 6.0 | 3 | 4.1 | 0.8 - 11.4 | 0.440  |
|  Cardiovascular | 15 | 8.9 | 5.1 - 14.3 | 6 | 8.1 | 3.0 - 16.8 | 1.000  |
|  Central Nervous System | 6 | 3.6 | 1.3 - 7.6 | 4 | 5.4 | 1.5 - 13.3 | 0.500  |
|  Dermatological | 8 | 4.8 | 2.1 - 9.2 | 0 | 0.0 | 0.0 - 0.0 | 0.111  |
|  Endocrine/Metabolic | 4 | 2.4 | 0.6 - 6.0 | 6 | 8.1 | 3.0 - 16.8 | 0.072  |
|  Gastrointestinal | 8 | 4.8 | 2.1 - 9.2 | 6 | 8.1 | 3.0 - 16.8 | 0.371  |
|  Genitourinary | 10 | 6.0 | 2.9 - 10.7 | 7 | 9.5 | 3.9 - 18.5 | 0.413  |
|  HEENT | 7 | 4.2 | 1.7 - 8.4 | 6 | 8.1 | 3.0 - 16.8 | 0.225  |
|  Hematological | 0 | 0.0 | 0.0 - 0.0 | 4 | 5.4 | 1.5 - 13.3 | 0.008  |
|  Musculoskeletal | 93 | 55.4 | 47.5 - 63.0 | 44 | 59.5 | 47.4 - 70.7 | 0.576  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 28 of 45

{28}

|   | Investigational N=168 |   |   | Control N=74 |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Adverse Events at the 24+ Month Endpoint | AEs | % | 95% Confidence Levels | AEs | % | 95% Confidence Levels | p-value  |
|  Neurological | 3 | 1.8 | 0.4 - 5.1 | 0 | 0.0 | 0.0 - 0.0 | 0.555  |
|  Other – Fell | 5 | 3.0 | 1.0 - 6.8 | 3 | 4.1 | 0.8 - 11.4 | 0.703  |
|  Other – Insect bite | 0 | 0.0 | 0.0 - 0.0 | 1 | 1.4 | 0.0 - 7.3 | 0.306  |
|  Other - Pregnancy - 7 Months Gestation | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Peripheral Nervous System | 4 | 2.4 | 0.6 - 6.0 | 3 | 4.1 | 0.8 - 11.4 | 0.440  |
|  Respiratory System | 4 | 2.4 | 0.6 - 6.0 | 4 | 5.4 | 1.5 - 13.3 | 0.253  |
|  Thrombosis/Thrombophlebitis | 5 | 3.0 | 1.0 - 6.8 | 1 | 1.4 | 0.0 - 7.3 | 0.670  |
|  Wound Problem | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Every unique adverse event was reported once, regardless of whether a single hip reported more than one instance of a particular adverse event. For example, if a hip reported 'musculoskeletal', then 'musculoskeletal' was listed once for that hip. However, if that same hip also reported 'cancer', then that adverse event was listed in addition to the 'musculoskeletal' adverse event.  |   |   |   |   |   |   |   |

The most frequent postoperative systemic adverse events for investigational subjects in the 36mm Subset Cohort were musculoskeletal, cardiovascular, gastrointestinal, HEENT, central nervous system, and genitourinary.

There were no systemic adverse events in the 36mm Subset Cohort that occurred with a higher incidence statistical significance. The hematological adverse event rate was significantly higher in the COP28 control group compared to the COC36 investigational group (see Table 13 below).

Table 13: Comparison of Frequency of Postoperative Systemic Adverse Events: 36mm Subset Cohort

|   | Investigational N=98 |   | Control N=40  |   |
| --- | --- | --- | --- | --- |
|  Adverse Events at the 24+ Month Endpoint | AEs | % | AEs | %  |
|  Cancer | 2 | 2.0 | 1 | 2.5  |
|  Cardiovascular | 11 | 11.2 | 4 | 10.0  |
|  Central Nervous System | 5 | 5.1 | 3 | 7.5  |
|  Dermatological | 3 | 3.1 | 0 | 0.0  |
|  Endocrine/Metabolic | 1 | 1.0 | 3 | 7.5  |
|  Gastrointestinal | 6 | 6.1 | 3 | 7.5  |
|  Genitourinary | 4 | 4.1 | 5 | 12.5  |
|  HEENT | 6 | 6.1 | 1 | 2.5  |
|  Hematological | 0 | 0.0 | 3 | 7.5  |
|  Musculoskeletal | 53 | 54.1 | 27 | 67.5  |
|  Neurological | 1 | 1.0 | 0 | 0.0  |
|  Other – Fell | 3 | 3.1 | 1 | 2.5  |
|  Other – Insect bite | 0 | 0.0 | 1 | 2.5  |
|  Peripheral Nervous System | 2 | 2.0 | 2 | 5.0  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 29 of 45

{29}

|  Adverse Events at the 24+ Month Endpoint | Investigational N=98 |   | Control N=40  |   |
| --- | --- | --- | --- | --- |
|   |  AEs | % | AEs | %  |
|  Respiratory System | 2 | 2.0 | 3 | 7.5  |
|  Thrombosis/Thrombophlebitis | 2 | 2.0 | 0 | 0.0  |
|  Every unique adverse event was reported once, regardless of whether a single hip reported more than one instance of a particular adverse event. For example, if a hip reported 'musculoskeletal', then 'musculoskeletal' was listed once for that hip. However, if that same hip also reported 'cardiovascular', then that adverse event was listed in addition to the 'musculoskeletal' adverse event.  |   |   |   |   |

#### 4. 36mm PMA Study Postoperative Operative Site Adverse Events

The most commonly reported postoperative operative site complications for investigational subjects were Trochanteric Bursitis, Musculoskeletal, Other – Squeaking, Pain, and Other – Clicking, Other – Iliopsoas Tendinitis, Pain: Thigh, and Wound Problem, respectively. There were no specific postoperative-operative site adverse events that occurred with a statistically significant higher proportion in COC36 investigational subjects. (See **Table 14** below).

**Table 14: Comparison of Frequency of Postoperative Operative Site Adverse Events: 36mm PMA Study: All Enrolled Cohort**

|  Adverse Events at the 24+ Month Endpoint | Investigational N=168 |   |   | Control N=74 |   |   | p-value  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  AEs | % | 95% Confidence Levels | AEs | % | 95% Confidence Levels  |   |
|  Acetabular Component Failure^{1} | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Acetabular Liner Failure^{2} | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Deep Infection | 2 | 1.2 | 0.1 - 4.2 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Dermatological | 3 | 1.8 | 0.4 - 5.1 | 0 | 0.0 | 0.0 - 0.0 | 0.555  |
|  Dislocation | 2 | 1.2 | 0.1 - 4.2 | 4 | 5.4 | 1.5 - 13.3 | 0.073  |
|  Femoral Component Loosening^{3} | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Fracture – Femoral Insertional FX^{4} | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Hematoma Requiring Drainage | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Heterotopic Bone Formation | 3 | 1.8 | 0.4 - 5.1 | 0 | 0.0 | 0.0 - 0.0 | 0.555  |
|  Muscle Weakness | 4 | 2.4 | 0.6 - 6.0 | 0 | 0.0 | 0.0 - 0.0 | 0.316  |
|  Musculoskeletal | 16 | 9.5 | 5.5 - 15.0 | 3 | 4.1 | 0.8 - 11.4 | 0.197  |
|  Other – Clicking | 7 | 4.2 | 1.7 - 8.4 | 1 | 1.4 | 0.0 - 7.3 | 0.441  |
|  Other – Contusion | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 30 of 45

{30}

|   | Investigational N=168 |   |   | Control N=74 |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Adverse Events at the 24+ Month Endpoint | AEs | % | 95% Confidence Levels | AEs | % | 95% Confidence Levels | p-value  |
|  Other – Fell | 3 | 1.8 | 0.4 - 5.1 | 0 | 0.0 | 0.0 - 0.0 | 0.555  |
|  Other – Hip Pain | 2 | 1.2 | 0.1 - 4.2 | 1 | 1.4 | 0.0 - 7.3 | 1.000  |
|  Other – Hip Snapping | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Other – Iliopsoas Tendinitis | 6 | 3.6 | 1.3 - 7.6 | 3 | 4.1 | 0.8 - 11.4 | 1.000  |
|  Other – Squeaking | 8 | 4.8 | 2.1 - 9.2 | 0 | 0.0 | 0.0 - 0.0 | 0.111  |
|  Other – Stiffness | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Other – Subsidence of Femoral Component | 0 | 0.0 | 0.0 - 0.0 | 1 | 1.4 | 0.0 - 7.3 | 0.306  |
|  Other – Vibration | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Pain | 8 | 4.8 | 2.1 - 9.2 | 2 | 2.7 | 0.3 - 9.4 | 0.728  |
|  Pain: Thigh | 6 | 3.6 | 1.3 - 7.6 | 3 | 4.1 | 0.8 - 11.4 | 1.000  |
|  Subluxation | 1 | 0.6 | 0.0 - 3.3 | 0 | 0.0 | 0.0 - 0.0 | 1.000  |
|  Trochanteric Bursitis | 17 | 10.1 | 6.0 - 15.7 | 4 | 5.4 | 1.5 - 13.3 | 0.323  |
|  Wound Problem | 6 | 3.6 | 1.3 - 7.6 | 1 | 1.4 | 0.0 - 7.3 | 0.679  |

Every unique adverse event was reported once, regardless of whether a single hip reported more than one instance of a particular adverse event. For example, if a hip reported 'deep infection', then 'deep infection' was listed once for that hip. However, if that same hip also reported 'trochanteric bursitis', then that adverse event was listed in addition to the 'deep infection' adverse event.

# Additional Notes:

1 This AE was documented for the 52 year old male Subject who had acetabular components revised at 2.92 years post-op (this Subject's second revision).
2 This AE was documented for the 59 year old female Subject who was revised for an acetabular liner fracture at 1.67 years post-op.
3 This AE was documented for the 52 year old male Subject who had femoral components revised at 0.58 years post-op (this Subject's first revision; the Subject was not withdrawn from the study because acetabular components were not revised).
4 A femoral fracture diagnosed one month after index THA; date of onset was stated as the date of index THA. The investigator indicated that the AE was not directly related to the device. The recommended treatment was protected weight bearing for 6 weeks.

For the 36mm PMA Study Subset Cohort, the most frequent postoperative operative site adverse events were Trochanteric Bursitis, Musculoskeletal, Pain, Pain: Thigh, Heterotopic Bone Formation, Muscle Weakness, and Other - Squeaking. There were no specific postoperative-operative site adverse events that occurred with a statistically significant higher proportion in COC36 investigational subjects (see Table 15 below).

Table 15: Comparison of Frequency of Postoperative Operative Site Adverse Events: 36mm Subset Cohort

|   | Investigational N=98 |   | Control N=40  |   |
| --- | --- | --- | --- | --- |
|  Adverse Events at the 24 month+ Endpoint | AEs | % | AEs | %  |
|  Acetabular Component Failure^{1} | 1 | 1.0 | 0 | 0.0  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 31 of 45

{31}

|  Adverse Events at the 24 month+ Endpoint | Investigational N=98 |   | Control N=40  |   |
| --- | --- | --- | --- | --- |
|   |  AEs | % | AEs | %  |
|  Deep Infection | 1 | 1.0 | 0 | 0.0  |
|  Dermatological | 2 | 2.0 | 0 | 0.0  |
|  Dislocation | 2 | 2.0 | 2 | 5.0  |
|  Femoral Component Loosening^{2} | 1 | 1.0 | 0 | 0.0  |
|  Hematoma Requiring Drainage | 1 | 1.0 | 0 | 0.0  |
|  Heterotopic Bone Formation | 3 | 3.1 | 0 | 0.0  |
|  Muscle Weakness | 3 | 3.1 | 0 | 0.0  |
|  Musculoskeletal | 7 | 7.1 | 2 | 5.0  |
|  Other – Clicking | 2 | 2.0 | 1 | 2.5  |
|  Other – Contusion | 1 | 1.0 | 0 | 0.0  |
|  Other – Fell | 1 | 1.0 | 0 | 0.0  |
|  Other – Hip Pain | 0 | 0.0 | 1 | 2.5  |
|  Other – Iliopsoas Tendinitis | 2 | 2.0 | 2 | 5.0  |
|  Other – Squeaking | 3 | 3.1 | 0 | 0.0  |
|  Other – Stiffness | 1 | 1.0 | 0 | 0.0  |
|  Other – Subsidence of Femoral Component | 0 | 0.0 | 1 | 2.5  |
|  Other – Vibration | 1 | 1.0 | 0 | 0.0  |
|  Pain | 4 | 4.1 | 2 | 5.0  |
|  Pain: Thigh | 4 | 4.1 | 2 | 5.0  |
|  Subluxation | 1 | 1.0 | 0 | 0.0  |
|  Trochanteric Bursitis | 13 | 13.3 | 3 | 7.5  |
|  Every unique adverse event was reported once, regardless of whether a single hip reported more than one instance of a particular adverse event. For example, if a hip reported 'deep infection', then 'deep infection' was listed once for that hip. However, if that same hip also reported 'trochanteric bursitis', then that adverse event was listed in addition to the 'deep infection' adverse event.  |   |   |   |   |
|  **Additional Notes:**  |   |   |   |   |
|  1 | This AE was documented for the 52 year old male Subject who had acetabular components revised at 2.92 years post-op (this Subject's second revision).  |   |   |   |
|  2 | This AE was documented for the 52 year old male Subject who had femoral components revised at 0.58 years post-op (this Subject's first revision; the Subject was not withdrawn from the study because acetabular components were not revised).  |   |   |   |

There were no specific postoperative-operative site adverse events that occurred with a statistically significant higher proportion in 36mm PMA study, for either the 36mm All Enrolled or the 36mm Subset Cohort. However, it was observed that in total there were 18 noise related postoperative-operative site adverse events (clicking, snapping, squeaking, or vibration) reported in 15 COC36 and 1 COP28 subjects. Some of these noise related AEs were deemed by the respective sites to be related to the device, and some were not, as displayed in **Table 16** below. All but one of the 12 device related noise AEs (reported in 11 COC36 subjects) were deemed by the respective investigators to be 'Mild' in severity; one instance of squeaking was reported to be 'Moderate' in severity. All but one of these 11 subjects stated satisfaction with their THA at the most recent 24+ month follow-up, and all of these 11

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 32 of 45

{32}

patients had a 24+ month Harris Hip score of 84 or higher (six had a 100).

**Table 16: Distribution of Device Related vs. Not Device Related (as determined by the sites) Postoperative Operative Site Noise Adverse Events: 36mm All Enrolled Cohort**

|   | OTHER-CLICKING | OTHER-HIP SNAPPING | OTHER-SQUEAKING* | OTHER-VIBRATION  |
| --- | --- | --- | --- | --- |
|  Possibly Device Related | 3 COC36 |  | 8 COC36 | 1 COC36  |
|  Not Device Related | 4 COC36, 1 COP28 | 1 COC36 |  |   |
|  *Note: After database lock, one further subject was reported to have squeaking in the study hip, for a total of 9 COC36 AEs related to squeaking. Out of these 9 hips, squeaking was only reproducible in 2 during clinical follow-up.  |   |   |   |   |

The applicant acknowledged that post-operative operative site noise related adverse events that are possibly related to the COC36 investigational device occurred with a higher frequency in the COC36 investigational group than in the COP28 control group, but considered these adverse events to be mild in severity, particularly given the clinical, pain, and satisfaction outcomes of the patients that exhibited these adverse events.

#### **b. Complications Grouped by Type of Adverse Event**

When AEs were grouped by type of AE (intraoperative, postoperative operative site, or systemic) for the 36mm PMA Study All Enrolled Cohort, there was a greater proportion of subjects with postoperative-operative site AEs in the investigational group (p-value = 0.018); there was no significant difference in the proportions of hips with systemic, intraoperative, or overall AEs across treatment groups (see **Table 17** below). In the 36mm Subset Cohort, there was not a significant difference in the proportions of hips with AEs in any category (overall, intraoperative, postoperative-operative site, or post-operative systemic; **Table 18** below). The total number of AEs grouped by type of AE (intraoperative, postoperative, operative site, or systemic) for the 36mm All Enrolled Cohort are reported in **Table 19**.

**Table 17: Comparison of Frequencies of Any Adverse Event (Per Hip Basis): 36mm All Enrolled Cohort**

|  Adverse Events at 24+ Endpoint | Investigational N=168 |   |   | Control N=74 |   |   | p-value  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |  AEs | % | 95% Confidence Levels | AEs | % | 95% Confidence Levels  |   |
|  Any Complication | 134 | 79.8 | 72.9 - 85.6 | 60 | 81.1 | 70.3 - 89.3 | 0.863  |
|  Intraoperative* | 5 | 3.0 | 1.0 - 6.8 | 1 | 1.4 | 0.0 - 7.3 | 0.670  |
|  Operative Site | 66 | 39.3 | 31.9 - 47.1 | 17 | 23.0 | 14.0 - 34.2 | 0.018  |
|  Systemic | 117 | 69.6 | 62.1 - 76.5 | 52 | 70.3 | 58.5 - 80.3 | 1.000  |

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 33 of 45

{33}

|   | Investigational N=168 |   |   | Control N=74 |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Adverse Events at 24+ Endpoint | AEs | % | 95% Confidence Levels | AEs | % | 95% Confidence Levels | p-value  |
|  Adverse events are reported on a per hip basis. Regardless of how many times a single hip had an intraoperative complication, for example, it was only counted once.  |   |   |   |   |   |   |   |
|  * The intraoperative AE tally presented in this table does not include one subject who received a metal-on-metal system subsequent to intraoperative ceramic liner fracture.  |   |   |   |   |   |   |   |

**Table 18: Comparison of Frequencies of Any Adverse Event (Per Hip Basis): 36mm Subset Cohort**

|  24+ Months | Investigational N=98 |   | Control N=40  |   |
| --- | --- | --- | --- | --- |
|  Adverse Events | AEs | % | AEs | %  |
|  Any Complication | 78 | 79.6 | 33 | 82.5  |
|  Intraoperative | 5 | 5.1 | 0 | 0.0  |
|  Operative Site | 36 | 36.7 | 10 | 25.0  |
|  Systemic | 70 | 71.4 | 30 | 75.0  |
|  Adverse events are reported on a per hip basis. Regardless of how many times a single hip had an intraoperative complication, for example, it was only counted once.  |   |   |   |   |

**Table 19: Comparison of Frequencies of Any Adverse Event (All events): 36mm All Enrolled Cohort**

|  Adverse Events (distinct events) | Investigational N=168 | Control N=74  |
| --- | --- | --- |
|  Any Complication | 417 | 237  |
|  Intraoperative | 5 | 1  |
|  Operative Site | 133 | 40  |
|  Systemic | 279 | 196  |
|  In this table, adverse events are reported on a per event basis, so that adverse events which were reported multiple times for a single hip were counted each time.  |   |   |

In order to understand the slightly higher proportion of post-operative operative site AEs in the investigational group, the sponsor examined those AEs which were deemed by the sites to be possibly device related, and those which were deemed by the sites not to be device related. **Table 20** below presents the number of subjects who experienced post-operative operative site adverse events which were deemed by the sites to be possibly device related, and also adverse events which were deemed to be not device related.

PMA P070026/S004: FDA Summary of Safety and Effectiveness Data

Page 34 of 45

{34}

**Table 20: Subjects with Device Related vs. Not Device Related (as determined by the (sites) Postoperative Operative Site Adverse Events: 36mm All Enrolled Cohort**

|  Adverse Events at 24+m Endpoint | Investigational N=168 |   | Control N = 74 |   | Fisher's Exact test p-value  |
| --- | --- | --- | --- | --- | --- |
|   |  Subjects | Percent | Subjects | Percent  |   |
|  OPERATIVE SITE: Device Related | 16 | 9.5 | 4 | 5.4 | 0.325  |
|  OPERATIVE SITE: Not Device Related | 61 | 36.3 | 16 | 21.6 | 0.025  |

Out of the 16 36mm All Enrolled Cohort subjects who were deemed to have experienced device related post-operative operative site adverse events, 11 experienced noise related adverse events. The sponsor attributed the disproportion in reported non-device related AEs to an increased rigor in investigator training and monitoring at the start of the 36mm arm of the PMA study, and concludes that with the exception of noise related AEs, there is not a significant difference across treatment groups in the proportions of subjects who experienced adverse events for reasons attributable to the COC36 investigational device.

#### **b. Distribution of Adverse Events over Time**

In **Tables 21 and 22**, a time course of the occurrence of post-operative systemic and operative site adverse events is displayed. An adverse event may be reported more than once per subject in these tables if the adverse event occurred more than once across time.

**Table 21: Time Course Occurrence of Postoperative Systemic Adverse Events: 36mm All Enrolled Cohort**

|  Complication | Interval  |   |   |   |   |   |   |   |   |   |   |   |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |…

---

**Source:** [https://fda-staging.innolitics.com/device/P070026S004](https://fda-staging.innolitics.com/device/P070026S004)

**Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact).

**Cite:** Innolitics at https://innolitics.com