← Product Code [NRA](/productcode/NRA) · P010014S105 # Oxford™ Cementless Partial Knee System (P010014S105) _Biomet Manufacturing Corp · NRA · Nov 22, 2024 · Orthopedic · APPR_ **Canonical URL:** https://fda-staging.innolitics.com/device/P010014S105 ## Device Facts - **Applicant:** Biomet Manufacturing Corp - **Product Code:** [NRA](/productcode/NRA.md) - **Decision Date:** Nov 22, 2024 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Orthopedic - **Attributes:** Therapeutic ## Indications for Use The Oxford™ Cementless Partial Knee System is indicated for use in unilateral knee procedures with osteoarthritis or avascular necrosis limited to the medial compartment of the knee. It is intended to be implanted without the application of bone cement for patients whose clinical condition would benefit from a shorter surgical time compared to the cemented implant. The device system is for prescription use. ## Device Story Medial unicompartmental knee prosthesis; consists of femoral component, tibial component, and mobile meniscal bearing. Femoral/tibial components implanted without bone cement via press-fit; meniscal bearing provides unconstrained articulation. Used in orthopedic surgery; implanted by orthopedic surgeons. Inputs: patient bone anatomy; outputs: restored joint function/alignment. Benefits: reduced surgical time compared to cemented implants. Healthcare providers use output to treat medial compartment osteoarthritis/avascular necrosis; clinical decision-making involves assessing patient bone stock and ligamentous stability. ## Clinical Evidence Prospective, multi-center, two-arm, randomized, controlled clinical study (IDE #G100123). 378 patients (241 cementless, 137 cemented). Primary endpoints: revision/removal/UADE, radiographic success, KSSA, KSSF at 22-24 months. Unilateral subgroup met non-inferiority margins for all endpoints. Bilateral subgroup showed increased safety concerns and failed non-inferiority for three effectiveness endpoints. ## Technological Characteristics Femoral/tibial components: CoCrMo alloy (ASTM F75) with plasma-sprayed titanium alloy (Ti-6Al-4V, ASTM F1580) and hydroxyapatite (ASTM F1185/ISO 13779-6) bilayer coating. Meniscal bearing: UHMWPE (ASTM F648) with Ti-6Al-4V wire and tantalum markers (ASTM F560). Unconstrained mobile bearing design. Sterilization: Gamma irradiation. ## Regulatory Identification This type of device is designed to allow for motion between the plastic tibial bearing and metal tibial baseplate components of a unicompartmental knee prosthesis. It is intended to replace part of a knee joint in order to relieve pain and restore knee function, for indications such as osteoarthritis and avascular necrosis. ## Predicate Devices - Oxford™ Meniscal Unicompartmental Knee System ([P010014](/device/P010014.md)) ## 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: Unicompartmental Knee Prosthesis Device Trade Name: Oxford™ Cementless Partial Knee System Device Procode: NRA Applicant's Name and Address: BIOMET MANUFACTURING CORP. Waterton Industrial Estate Bridgend, Wales CF31 3XA United Kingdom Date(s) of Panel Recommendation: None Premarket Approval Application (PMA) Number: P010014/S105 Date of FDA Notice of Approval: November 22, 2024 The original PMA P010014 was approved on April 21, 2004, and is intended for use in individuals with osteoarthritis or avascular necrosis limited to the medial compartment of the knee and is intended to be implanted with bone cement. The SSED to support the indication is available on the CDRH website and is incorporated by reference here. The current supplement was submitted to expand the indication for the Oxford™ Cementless Partial Knee System. # II. INDICATIONS FOR USE The Oxford™ Cementless Partial Knee System is indicated for use in unilateral knee procedures with osteoarthritis or avascular necrosis limited to the medial compartment of the knee. It is intended to be implanted without the application of bone cement for patients whose clinical condition would benefit from a shorter surgical time compared to the cemented implant. The device system is for prescription use. # III. CONTRAINDICATIONS - Infection, sepsis, and osteomyelitis - Use in simultaneous bilateral surgery or planned staged bilateral procedures - Use in the lateral compartment of the knee - Rheumatoid arthritis or other forms of inflammatory joint disease PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 1 of 63 {1} - Revision of a failed prosthesis - Insufficiency of the collateral, anterior or posterior cruciate ligaments which would preclude stability of the device - Disease or damage to the lateral compartment of the knee except for a medial ulcer - Uncooperative patient or patient with neurologic disorders who are incapable of following directions - Osteoporosis - Metabolic disorders which may impair bone formation - Osteomalacia - Distant foci of infections which may spread to the implant site - Rapid joint destruction, marked bone loss or bone resorption apparent on roentgenogram - Vascular insufficiency, muscular atrophy, neuromuscular disease - Incomplete or deficient soft tissue surrounding the knee - Charcot's disease - A fixed varus deformity (not passively correctable) of greater than 15 degrees - A fixed flexion deformity (not passively correctable) of greater than 15 degrees # IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the Oxford™ Cementless Partial Knee System labeling. # V. DEVICE DESCRIPTION The Oxford™ Cementless Partial Knee System is a medial, unicompartmental knee prosthesis consisting of three components: a femoral component to substitute the distal femoral bone; a tibial component to substitute the proximal tibial bone; and an unconstrained mobile meniscal bearing which is placed between the two components. The femoral and tibial components of the Oxford™ Cementless Partial Knee System are intended to be implanted without bone cement. ![img-0.jpeg](img-0.jpeg) Figure 1: Oxford™ Cementless Partial Knee System The Oxford™ Cementless Partial Knee femoral and tibial components are manufactured from CoCrMo alloy (ASTM F75), and the bone contacting surfaces of the implants are coated with a plasma sprayed titanium alloy powder (Ti-6Al-4V per ASTM F1580). The femoral and tibial components bone contacting surfaces are then coated a second time PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 2 of 63 {2} with a plasma sprayed hydroxyapatite (HA) powder (ASTM F1185 and ISO 13779-6). The meniscal bearing is made of ultra-high molecular weight polyethylene (UHMWPE per ASTM F648), embedded with a titanium (Ti-6Al-4V per ASTM F136 and ISO 5832-3) wire and two tantalum balls (ASTM F560 and ISO 13782) to act as radiological markers. ## Device Components ### *Femoral Component* The cementless femoral component is available in five sizes (Extra Small, Small, Medium, Large, and Extra Large) which may be used on either the left or right knee. The femoral component has two pegs incorporated into the design to provide location to the patients prepared bone. The femoral component features a primary stepped peg with a distal diameter sufficient to provide initial fixation through a press-fit in the patient’s prepared femur. ### *Tibial Component* The tibial components are anatomic in design with specific variants intended for use in each of the left and right knee. Each component is approximately semi-circular in shape, extending anteriorly for optimum bone coverage. The tibial component is available in seven size and in left and right configurations (AA, A, B, C, D, E, F), which increases in the medial lateral (M/L) and anterior-posterior (A/P) dimensions. The inferior surface of the tibial component features a distally protruding keel for initial location of the implant to the patient’s prepared bone. The underside surface of the tibial component features the same dual coating as the femoral component. ### *Meniscal Bearings* The meniscal bearing is available in a range of sizes to match the femoral component sizes and is available in eight thicknesses (ranging from 3mm to 9mm). The meniscal bearings are anatomical in design and have separate variants for implantation in the left and right knee. ## VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several other alternatives for the correction of osteoarthritis or avascular necrosis limited to the medial compartment of the knee. Each alternative has its own ---PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 3 of 63 {3} advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle. The following alternative practices and procedures can be used to treat osteoarthritis or avascular necrosis limited to the medial compartment of the knee: Alternative Surgical Procedures - Hemi-arthroplasty: Only one joint surface is replaced - Osteotomy: Realignment of the bone with or without removal of a portion of the bone - Knee arthrodesis: Surgical immobilization of the knee joint - Total Knee Arthroplasty: the entire knee joint is replaced Non-Surgical Treatments - Alternative non-surgical procedures - Cortisone injection - Hyaluronic injection - Physical therapy - Ambulatory (walking) aides - Arthritis medication # VII. MARKETING HISTORY The Oxford™ Cementless Partial Knee System is commercially available in the following countries outside the USA: - Albania - Argentina - Bosnia and Herzegovina - Canada - China - Ecuador - Egypt - EU - Hong Kong - Indonesia - Iran - Israel - Japan - Kazakhstan - Lebanon - Malaysia - Mexico - New Zealand - Russia - Serbia - Singapore - Sri Lanka - Thailand - Turkey - UAE - Ukraine - Vietnam The Oxford™ Cementless Partial Knee System has been implanted in over 300,000 procedures outside the U.S. since 2013. The device has not been withdrawn from marketing for any reason related to its safety or effectiveness. PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 4 of 63 {4} ## **VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH** Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device: Avascular Necrosis Bearing Dislocation/Disassociation Clicking/Popping/Crepitus/Grinding Effusion/Swelling/Edema Femoral Implant Loosening Instability Other Ipsilateral Knee Related Adverse Event Pain (progressive/persistent) Stiffness/Limited ROM (progressive/persistent) Subsidence Tibial Fracture Tibial Implant loosening For the specific adverse events that occurred in the clinical study, please see Section X below. ## **IX. SUMMARY OF NON-CLINICAL STUDIES** ### **A. Laboratory Studies** Performance testing was conducted for the Oxford™ Cementless Partial Knee System and testing from the currently approved Oxford™ Meniscal Unicompartmental Knee System was leveraged to demonstrate that the Oxford™ Cementless Partial Knee System will perform as intended. Tests performed are listed here: - Contact Area & Contact Pressure - Range of motion evaluation - Femoral Component Fatigue Strength - Tibial Component Fatigue Strength - Constrain/Dislocation - Wear simulation testing - MR Compatibility evaluation - Cadaveric study A summary of each test is provided in the Table below. **Table 1: Summary of Non-Clinical Performance Testing** PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 2 of 63 {5} | Evaluation | Test | Acceptance Criteria | Results | | --- | --- | --- | --- | | Contact Area & Contact Pressure | Analysis of CAD models using Siemens NX12. CAD models of Extra Small and Extra Large Oxford Tibial Bearings articulating against compatible sizes of Femoral and Tibial components. | The contact area and contact stress of the femoral implant and Oxford cemented bearing shall be documented, through a knee range of motion of 0°, 15°, 30°, 60°, 90°. The contact area and contact stress of the tibial implant and Oxford cemented bearing shall be documented, through a knee range of motion of 0°, 15°, 30°, 60°, 90°. | Femoral implant to bearing contact area was found to be 381.68mm² and 714.43mm² for the Extra Small and Extra Large implants respectively. Tibial implant to bearing contact area was found to be a maximum of 462.42mm² and 889.49 mm² for the Extra Small and Extra Large bearing implants respectively. | | Range of Motion | Analysis of CAD models using Siemens NX12. CAD models of Extra Small and Extra Large Oxford Tibial Bearings articulating against compatible sizes of Femoral and Tibial components. | The femoral and bearing range of motion must have a range that covers at least 0° – 110°. | The analysis of contact area shows that full contact is maintained between the bearing and femoral component up to at least 90° flexion. At 135° flexion, the Extra Small and Extra Large bearings respectively provide contact areas of 223.28mm² and 413.18mm², which remains greater than half the contact area at 0° flexion. The femoral component and the bearing have spherical articulating surfaces with no positive features protruding beyond the spherical surfaces. The devices do not limit range of motion and a high level of contact is maintained to at least 135°. | | Femoral Component Fatigue Strength | Physical testing, with load based on ISO 7206- | Femoral implant shall withstand a peak load of 1.61 kN for 5 million cycles without crack formation, visual damage or articular surface dimensional deformation greater than manufacturing tolerances. | All samples survived 5 million cycles at 1.61kN peak load without cracks or visual damage, and remained within the manufacturing tolerance. | | Tibial Component Fatigue Strength | Physical with load based on ISO 7206. | Tibial implant shall withstand a peak load of 1.61 kN under cyclic loading for 5 million cycles without crack formation, visual damage or articular surface dimensional deformation greater than manufacturing tolerances. | All samples survived 5 million cycles at 1.61kN peak load without cracks, visual damage, or dimensional deformation that would take them outside the manufacturing tolerance. | | Constraint / Dislocation | Empirical data review: Review of device geometry, indications/contraindications, and Post Market Surveillance data | The load required to induce A/P subluxation shall be documented. The load required to induce M/L subluxation shall be documented. The torque required to induce I/E rotational subluxation shall be documented. | The design of the Oxford Partial Knee was found to provide no constraints on relative motion of the implants. The sphere-on-sphere articulation of the femoral component on the bearing, and the flat-on-flat articulation of the bearing on the tibial implant, allow the bearing and femoral component to translate freely in the A/P and M/L direction relative to the tibia, and allow the bearing, femoral component, and tibial component to rotate freely internally and externally relative to each other. The loads required to induce subluxation are dependent on the patient's anatomy and not on the device design. | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 3 of 63 {6} | Wear | 1. Wear testing per ISO 14243-1:2002 with amendments to reflect some changes in ISO 14243-1:2009 2. Wear testing was performed under ISO 14243-1 load control derived kinematics over 10 million test cycles on worst cased aged bearing per ASTM F2003 | 1. Tibiofemoral wear shall be evaluated per ISO 14243. Mean wear rate for the medial compartment shall be no greater than 21.70mm³/10⁶ cycles. 2. Informative test, no acceptance criteria applied | 1. Mean wear rate of 19.57mm³/10⁶ cycles for the medial compartment specimens. The acceptance criteria were satisfied. 2. Mean linear gravimetric wear rate of 8.60 mg/Mc ± 3.76 mg/Mc | | --- | --- | --- | --- | | MR Compatibility Evaluation | Research Analysis/Adoption | Suitable for labeling as "MR Conditional". | Suitable for MRI use under the following conditions: Static Magnetic Field (B0) Orientation: Horizontal, Cylindrical Bore Static Magnetic Field Strength (B_{0}): 1.5 T or 3.0 T Maximum Spatial Field Gradient: 25 T/m (2500 Gauss/cm) RF Polarization (Formerly RF Excitation): Circularly Polarized (CP) RF Transmit Coil Type: Integrated Whole Body Transmit Coil Operating Mode: Normal Operating Mode Maximum Whole-Body SAR: 2 W/kg 15 minutes continuous RF followed by a wait time of 6 minutes | ### Coating Characterization Characterization of the plasma spray and bilayer coating was performed according to FDA Guidance for Industry on the Testing of Metallic Plasma Sprayed Coatings on Orthopedic Implants to Support Reconsideration of Postmarket Surveillance Requirements (February 2, 2020). The following mechanical testing conducted: - Microstructure of the modified surface - Surface thickness per ASTM F1854 - Void size per ASTM F1854 - Mean volume percent of voids per ASTM F1854 - Mechanical Properties of the modified surface - Shear fatigue strength per ASTM F1160 - Static shear strength per ASTM F1044 - Static tensile strength per ASTM F1147 - Abrasion resistance per ASTM F1978 A summary of the Oxford™ Femur and Oxford™ Tibia component validation is provided in the table below. **Table 2: Mechanical Testing of Coatings** | Test Method / Applicable Standards | Acceptance Criteria | Results : Femur Plasma Spray Titanium coating | Results : Tibia Plasma Spray Titanium coating | | --- | --- | --- | --- | | ASTM F1044 (Shear Static) | ≥ 20 MPa | 27.97 ± 0.34 MPa | 41.95 ± 9.01 MPa | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 4 of 63 {7} | ASTM F1160 (Shear Fatigue) | ≥ 10,000,000 cycles | All samples met 10,000,000 cycles | All samples met 10,000,000 cycles | | --- | --- | --- | --- | | ASTM F1147 (Static Tensile Adhesion) | ≥ 22 MPa | 47.49 ± 9.06 MPa | 33.13 ± 5.98 MPa | | ASTM F1854 (Thickness) | 386 μm to 1,010 μm | 802.56 ± 45.32 μm | 757.22 ± 71.37 μm | | ASTM F1854 (Porosity) | 30% to 70% | 38.08 ± 2.53 % | 41.44 ± 4.72 % | | ASTM F1854 (Pore Size) | 100 μm to 1,000 μm | 137.51 ± 7.85 μm | 170.02 ± 13.34 μm | | ASTM F1978 (Taber Abrasion) | Weight loss max. 65mg | 29.03 ± 8.48 mg | 34.78 ± 3.16 mg | In addition, the hydroxyapatite coating was characterized according to FDA guidance 510(k) Information Needed for Hydroxyapatite Coated Orthopedic Implants (February 20, 1997). The hydroxyapatite coating met all applicable characterization requirements. ### Biocompatibility The implants are manufactured using implant grade materials and the instruments are manufactured using standard instrumentation materials. The biological evaluation per ISO-10993 was based on review of the materials, manufacturing vendors, manufacturing validation testing (cytotoxicity, sensitization, systemic toxicity, pyrogen testing, intracutaneous irritation), and manufacturing reagents. The risk assessment confirmed that there are no risks associated with the biocompatibility of the Oxford™ Cementless Partial Knee System. ### B. Animal Studies A nonclinical Good Laboratory Practice (GLP) implantation study was performed to evaluate the local effects including bone healing response of the two-representative bone-contacting samples of the Oxford™ Cementless Partial Knee System, i.e. CoCr plasma sprayed with HA (Test Article 1 (T1)) and CoCr plasma sprayed with Ti6Al4V alloy and HA on top (Test Article 2 (T2)). The test articles were compared to the bone-contacting material compounds of the marketed Oxford™ Cemented Partial Knee System (control article (C), polished CoCr). Articles were tested in a femoral condyle and humeral model in sheep for 4, 13 and 26 weeks. Local tissue effects including bone healing response were evaluated based on macroscopic, histopathologic and histomorphometric analyses. Local tissue effects evaluation showed a slight to moderate inflammatory reaction, which was similarly observed in the three groups, leading to minimal to no reaction of both T1 and T2 when compared to C, at the three time points. Slight to moderate numbers of macrophages containing blue/grey granular material of unknown nature were rarely observed in draining lymph nodes mainly for the T1 and T2 articles (but also suspected in the C group). Even though it is doubtful due to their probable observation in the C group, there is a possibility that these macrophages might correspond to drained macrophages containing phagocytosed hydroxyapatite from the PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 5 of 63 {8} implantation sites. The hydroxyapatite coating of T1 and T2 seemed less thick and sometimes discontinuous over time. Following the complete necropsy, no findings on the organs could be linked to the implanted articles. Regarding bone healing response, bone neoformation was similar for all articles. Osteoconduction was similar for T1 compared to C, and slightly less advanced for T2 after 26 weeks. Osseointegration was greater for T1 and T2 compared to C after 26 weeks. Bone remodeling similarly progressed among the three groups over time. Based on the Reactivity Ranking, at four weeks, thirteen weeks and twenty-six weeks after implantation, the test articles scored <3 and were considered to have minimal to no reaction when compared to the control article. Further animal studies were not necessary to support the safety and effectiveness of the Oxford™ Cementless Partial Knee System implants. ### C. Additional Studies Additional testing was performed as outlined in the table below. Table 3: Additional Testing Summary | Test | Acceptance Criteria | Results | Analysis Type | | --- | --- | --- | --- | | Sterilization | Gamma irradiation sterilization process is used. The sterilization dose is established in accordance with Method VDmax20 from ISO/TS 13004:2022 and Method VDmax25 from ISO 11137-2:2015. Devices must have a sterility assurance of at least 10^{-6}. | Passed | Validation was performed on the largest size Femoral which was determined to create the worst case conditions for the coated metal components. | | Endotoxin | Total endotoxin should be less than 20 endotoxin units (EU)/Device. | Passed | ANSI/AAMI ST72:2019 Limulus amebocyte lysate (LAL) test performed on Cementless Oxford Femoral and Tibial component. Results confirms that the testing limit of 20 endotoxin units per construct is met. | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 6 of 63 {9} | Package performance | Packaging integrity tests conducted in simulated testing at baseline, 1, 3, 5, 7, and 10 years, and real time aging at 1, 3, 5, 7, and 10 years: 1.Peel strength; 2.bubble testing; 3.visual heat seal inspection; 4.visual inspection / label copy. | Passed | Samples processed under normal conditions at the minimum sealing parameters were evaluated via visual inspection, seal integrity (ASTM F-1886), bubble leak testing (ASTM F-2096), aseptic presentation (ISO 11607), peel strength (ASTM F-88), and label legibility. Validation was completed for Nylon pouch Primary sterile barrier packaging. | | --- | --- | --- | --- | | Package stability testing | Seal strength values must generate a Ppk process capability minimum value of 0.68 utilizing 0.75lb/inch as the LSL per interval per location | Passed | Seal strength testing was completed for Nylon pouch Primary sterile barrier packaging. Seal Strength demonstrated a Ppk capability of 2.09. | | Cleaning validation | Visually free of manufacturing material or cosmetic defects. Total Organic Carbon ≤1.25 mg/part Non-Polar Solvent Extractable ≤2.0 mg/part Non-Soluble Water Extractable ≤3.0 mg/part Soluble Water Extractable ≤4.0mg/part | Passed | Cleaning validation was conducted on the implants based on worst case for geometry and surface area, therefore one tibia and one femur parts were used. | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 7 of 63 {10} | | Bacterial Endotoxin Test (BET) ≤20 EU/device Cytotoxicity, MEM elution method ≤ Grade 2 | | | | --- | --- | --- | --- | The shelf life for the Oxford™ Cementless Partial Knee System based on the testing above is 10 years for the metal components and 5 years for the polyethylene components. ## **X. SUMMARY OF PRIMARY CLINICAL STUDY** The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of unicompartmental knee arthroplasty with the Oxford™ Cementless Partial Knee System originally for use in individuals with osteoarthritis or avascular necrosis limited to the medial compartment in the knee in the US under IDE # G100123 (the “Oxford™ Cementless IDE Study”). Data from this clinical study were the basis for the PMA approval decision for the following modified Intended Use/Indications for Use statement: The Oxford™ Cementless Partial Knee System is indicated for use in unilateral knee procedures with osteoarthritis or avascular necrosis limited to the medial compartment of the knee. It is intended to be implanted without the application of bone cement for patients whose clinical condition would benefit from a shorter surgical time compared to the cemented implant. A summary of the clinical study is presented below. ### **A. Study Design** Patients were treated between October 2013 and November 2018. The database for this Panel Track Supplement reflected data collected through November 2020 and included 378 patients. There were 9 investigational sites. The study was a prospective, multi-center, two-arm, single-blinded, randomized, controlled clinical study. Each knee included in the study was randomized to receive treatment with either a Oxford™ Cementless Partial Knee (Investigational arm) or a Oxford™ Meniscal Unicompartmental Knee (Control arm). An imbalanced, blocked randomization (2:1, Cementless vs. Cemented) was used. The study included both Unilateral and Bilateral knees. In the case of Bilateral knees, the subject received the same knee implant for the second surgery as was prescribed by the randomization assigned for the first knee. Unilateral and bilateral cases were determined retrospectively. Subjects receiving a single implant were classified as a unilateral case. Subjects receiving two study devices (staged or simultaneously) were considered as bilateral cases from the start of the first knee being implanted, such that all case data was considered and analyzed as PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 8 of 63 {11} a bilateral case. Subjects implanted with a single study device and later receiving a non-study device in the contralateral knee were also considered bilateral cases. The study was designed to show that the investigational device (Cementless) was non-inferior to the Control device using four co-primary study endpoints. This was shown using a closed testing method in which each of the primary endpoints (described below) are compared using $\alpha=0.05$. Study success required that the Cementless group successfully demonstrated non-inferiority when compared to the Control group for all four of the individual primary endpoints. The sample size was calculated based on the endpoint of Radiographic Success, which was the endpoint which required the largest sample size to maintain 90% power. A success rate of 95% was used for the estimate of Radiographic Success, which resulted in a sample size of 191 Cementless device vs. 96 Control (5% type I error rate, 90% power). The sample size was increased by 10% to allow for possible exclusions in the primary analysis due to bilateral patients who may not be poolable with the unilateral cases, as well as attrition of up to 15%. This gave a theoretical sample size of 383 total subjects (255 Cementless vs. 128 Control). After completion of enrollment, it was discovered that five (5) subjects were implanted with an earlier version of the device and had to be excluded from the data analysis. This resulted in a final sample size of 378 subjects. The actual per-group sample size is slightly different from the theoretical per-group sample size due to the randomization scheme which was blocked within-site and per-patient. The per group, Per Protocol final sample sizes were 241 Cementless vs. 137 Control. An independent laboratory was contracted to review, analyze and report laboratory findings including the condition of the explanted devices. All radiographs were reviewed by an independent primary reviewer. If the primary reviewer identified a radiographic failure, the films deemed a failure, along with a randomly selected statistical sample of current non-failures were sent to a qualified, independent second reviewer. If the results of the second review differed significantly from the first, an independent, qualified third reviewer was employed to review the films. All knee-related adverse events (AEs) were reviewed by an independent Clinical Events Committee (CEC) consisting of three independent orthopaedic surgeons and adjudicated for seriousness, device-relatedness, severity, and outcome. For completeness, all general AEs were examined by one of the CEC members to determine if any of those events should have been classified as a knee-related event and adjudicated accordingly. The control group was the Oxford™ Cemented Partial Knee, which is a legally marketed alternative. ---PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 9 of 63 {12} ## 1. Clinical Inclusion and Exclusion Criteria Enrollment in the Oxford™ Cementless IDE study was limited to patients who met the following inclusion criteria: - Patients with a pre-operative Knee Society Assessment Score of <70 - Patients undergoing primary partial knee arthroplasty as Unilateral arthroplasty or Bilateral arthroplasty, simultaneously or otherwise - Patients diagnosed with osteoarthritis or avascular necrosis limited to the medial compartment of the operative knee joint - Male or female patients who are at least 21 years of age at the time of surgery - Patients with full thickness cartilage loss, with or without bone loss in the medial compartment - Patients with functionally intact ACL and PCL - Patients who need to obtain relief of pain and/or improved function in their knee - Patients with fixed flexion deformity < 15° - Patients who are able to follow post operative care instructions - Patients who are willing and able to return for scheduled follow-up evaluations - Patients in which natural alignment can be restored - Patients who have completed a valid, IRB approved Informed Consent Form - Patients with childbearing potential who voluntarily agree to prevent pregnancy for 2 years following device implantation Patients were not permitted to enroll in the Oxford™ Cementless IDE study if they met any of the following exclusion criteria: - Patients with a pre-operative Knee Society Assessment Score of ≥ 70 - Patients in which the device would be used to revise a failed prosthesis - Patients who are less than 21 years of age at the time of surgery - Disease or damage to the lateral part of the knee that in the investigator's opinion contraindicates a partial knee replacement - Patients diagnosed with rheumatoid arthritis or other forms of inflammatory joint disease - Patients diagnosed with a failed upper tibial osteotomy in the operative knee - Patients diagnosed with post-traumatic arthritis after tibial plateau fracture - Patients who have had a patellectomy - Patients with a flexion deformity > 15° - Patients with a fixed varus deformity > 15° - Patients who have rapid joint destruction, marked bone loss or bone resorption apparent on roentgenogram - Patients with a fused knee on operative side - Patients who have active or suspected infection, local or systemic, that, in the opinion of the investigator, may put patients at undue risk. PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 10 of 63 {13} - Patient with pre-existing condition(s) that may interfere with the survival of the implant or their outcomes, including: - Sickle Cell Anemia - Lower extremity muscular atrophy - Neuromuscular disease - Vascular insufficiency - Metabolic Disorders which impair bone formation - Paget's Disease - Charcot's Disease - Osteomalacia - Severe Osteoporosis - Patients with clinical conditions that may limit follow-up (in the opinion of the investigator) including; - Immuno-compromised conditions (i.e. HIV) - Hepatitis - Tuberculosis - Neoplastic disease such as cancer of the prostate, lung, stomach, cervix, etc. - Chronic renal failure - Organ transplant (i.e. heart, liver, lung, etc.) recipients - Known disease process that in the opinion of the investigator may limit long term (4 year) follow up (i.e. multiple sclerosis, leukemia, lymphoma, etc.) - Patients diagnosed with Parkinson's or Alzheimer's Disease - Patients who have had an above-knee amputation in the contralateral leg - Instability or deformity of the ligaments and/or surrounding soft tissue, which would preclude stability of the prostheses - Patients with a known metal allergy - Prisoners or, individuals who are known to be abusing drugs or alcohol or are mentally incompetent - Patients who have received systemic steroids within the past 6 months or steroid injection into the affected knee within the previous 6 weeks prior to enrollment - Patients who are pregnant - Patients with severe valgus or varus knees (valgus or varus angulation of more than 20°) where collateral ligament, iliotibial band, or popliteal release is required - Patients who refuse to sign the IRB approved Informed Consent Form - Participation in an interventional clinical research study procedure, other than a Bilateral knee arthroplasty in this study, within the past 12 months - Patients with a history of osteomyelitis or sepsis of the index knee - Patients who require patellar resurfacing - Patients who are not skeletally mature - Patients who have had a total hip replacement procedure <18 months prior to entering the study PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 11 of 63 {14} - Patients who have had a contralateral non-study knee replacement procedure <18 months prior to entering the study - Patients who are found intraoperatively to have inadequate bone stock or other conditions that contraindicate a partial knee replacement # 2. Follow-up Schedule All patients were scheduled to return for follow-up examinations at 6 weeks (±3 weeks), 6 months (±1 month), 1 year (±2 months), 2 years (±2 months) and annually (±2 months) until all subjects completed the 2-year follow-up visit postoperatively. After the 2-year follow-up, patients were examined clinically and radiographically on an annual basis until all available study patients completed the 2-year follow-up. Preoperative information collected and assessments performed included informed consent, medical history, demographics, concomitant medications, Knee Society Assessment Score (KSSA), Knee Society Function Score (KSSF), and Oxford Knee Score (OKS). Postoperatively, the objective parameters measured during the study included a radiographic evaluation, KSSA, KSSF, OKS, and a patient satisfaction questionnaire, which were all collected at all visits. Adverse events and complications were recorded at all visits. The Study Assessment Schedule and Follow-Up Windows Table outlines the study data collection. Table 4: Study Assessment Schedule | Form Name | Pre-op | Operative | 6 Week | 6 Month | 1 Year | 2 Year | Annually* | | --- | --- | --- | --- | --- | --- | --- | --- | | Informed Consent | X | | | | | | | | Patient History & Record of Medications | X | | | | | | | | Patient Operation | | X | | | | | | | Knee Society Score (KSS) | X | | X | X | X | X | X | | Oxford Knee Score | X | | X | X | X | X | X | | Patient Satisfaction Questionnaire | | | X | X | X | X | X | | Radiographic Evaluation (Independent Reviewer) | | | X | X | X | X | X | | Protocol Deviation | As appropriate | | | | | | | | Adverse Event | As appropriate | | | | | | | | Study Completion | As appropriate | | | | | | | | Adverse Event Determination | As appropriate | | | | | | | Table 5: Follow-Up Visit Windows | Interval | Follow-up Window | Months Post-op | Days Post-op | | --- | --- | --- | --- | | 6 Week | +/- 3 weeks | 1-2 | 21-63 | | 6 Month | +/- 1 month | 5-7 | 153-214 | | 1 Year | +/- 2 months | 10-14 | 304-426 | | 2 Years | +/- 2 months | 22-26 | 669-791 | | 3 Years | +/- 2 months | 34-38 | 1035-1157 | | 4 Years | +/- 2 months | 46-50 | 1400-1522 | | 5 Years | +/- 2 months | 58-62 | 1765-1887 | | 6 Years | +/- 2 months | 70-74 | 2130-2252 | | 7 Years | +/- 2 months | 82-86 | 2495-2617 | | 8 Years | +/- 2 months | 94-98 | 2860-2982 | | 9 Years | +/- 2 months | 106-110 | 3226-3347 | | 10 Years | +/- 2 months | 118-122 | 3591-3712 | The key timepoints are shown below in the tables summarizing safety and effectiveness. PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 12 of 63 {15} 3. Clinical Endpoints Safety: With regards to safety, all adverse events were recorded, described, and compared for Cementless vs. Control Groups. The twenty-four months safety endpoint data for the Cementless vs. Control Groups was independently adjudicated by a Clinical Events Committee in accordance with applicable FDA guidance documents to ensure appropriate classification.1,2 The twenty-four month safety endpoint data was compared and analyzed for all index knee-related adverse events. These adverse events were summarized by knee and included the number of adverse events involving the index knee for each patient. The safety adverse event reporting was performed for the type of knee procedure to include All Knees, Bilateral Knees, and Unilateral Knee procedures. The safety and adverse event reporting was also performed for the Per-Protocol (PP) and Intent-to-Treat (ITT) populations. The summary of adverse event data for the Cementless vs. Control Groups and the proportions of index knees experiencing adverse events for both groups and relative risk with associated 95% Confidence Intervals (CI) were reported for the following parameters. - Subjects with Adverse Events of the index knee, n (%) - Subjects with Device-Related Adverse Events of the index knee, n (%) - Total number of Adverse Events of the index knee, n (%) - Device Non-Related Non-Serious - Device Non-Related Serious - Device-Related Non-Serious - Device-Related Serious - Subjects with device revision/removal - Subjects with device removal/conversion to total knee arthroplasty The twenty-four months safety endpoint data for the Cementless vs. Control Group was then independently adjudicated by a Clinical Events Committee in accordance with applicable FDA guidance documents to ensure appropriate classification. The summary of Adverse Event data for the Cementless vs. Control Groups and the proportions of index knees experiencing adverse events were reported for the following parameters. - Adverse Event Severity, n (%) - Mild - Moderate - Severe - Adverse Event Outcome - Device Revision/Removal/Reoperation - Study Withdrawal PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 13 of 63 {16} ○ Tolerated ○ Not Tolerated ○ Resolved ○ Not Resolved This was performed for all adverse events and for those adverse events that were classified as device-related. An index knee had to have all adverse events classified as either Tolerated or Resolved to be classified within that category. Effectiveness: With regards to effectiveness, the primary endpoints in this study consisted of four individual co-primary endpoints: 1. Absence of Revision/Removal/Unanticipated Adverse Device Effect (UADE) at any time point through 24 months follow-up 2. Radiographic Success at 22+ months 3. The Knee Society Assessment Score (KSSA) at 22+ months 4. The Knee Society Function Score (KSSF) at 22+ months The 22+ Month interval was defined as the first availability of data for that endpoint starting at 22 months after the index procedure. The Radiographic Success at 22+ months co-primary endpoint was modified to allow the use of radiographs that were completed outside of the 22-26 months study interval window to follow the protocol-defined plan for analysis (use of 22+ month radiographic data). The reason for the missed assessment within the study interval window at 24-months was shown along with the other adverse event data reported for these subjects to support the use of this specific datapoint beyond the 24-month scheduled assessment. The radiographic success is based upon the proportion of radiographically successful knees and all device revisions and removals that are classified as failures. Additionally, the KSSA and KSSF co-primary endpoints for all cases (combined, unilateral, and bilateral) were evaluated with 22+ month data and therefore also modified from the original co-primary endpoints. The Absence of Revision/Removal/Unanticipated Adverse Device Effect (UADE) endpoint was evaluated at the 24-month timepoint. With regard to success/failure criteria, a successful radiographic endpoint was defined as a knee that met the following criteria at 22+ months: 1. Absence of osteolysis 2. No migration/subsidence of any femoral or tibial component 3. Absence of fractured component Conversely, a radiographic failure is defined as follows: 1. Presence of osteolysis defined as a radiolucency that is both progressive and is greater than 3 mm at its maximum interface in two or more contiguous zones OR a bony destructive lesion that is progressive in nature. PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 14 of 63 {17} 2. Migration/subsidence of any femoral or tibial component defined as a component migration/subsidence of > 3 mm as compared to 6 week radiographs. 3. A component fracture. Each co-primary effectiveness endpoint was considered successful for the study overall if the Cementless group was non-inferior to the Control Group, according to the following parameters: 1. Absence of revision/removal/UADE: The proportion of knees that were free from revision/removal/UADE in the Cementless group was non-inferior to that of Control knees using a 10% margin of non-inferiority at 24 Months. 2. Radiographic Success at 22+ Months: The proportion of radiographically successful knees in the Cementless group was non-inferior to the proportion of radiographically successful knees in the Control group using an 8% margin of non-inferiority. 3. KSSA at 22+ Months: The mean KSSA for the Cementless group was non-inferior to the mean KSSA for the Control group using a 6.4-point margin of non-inferiority. 4. KSSF at 22+ Months: The mean KSSF for the Cementless group is non-inferior to the mean KSSF for the Control group using a 9.2-point margin of non-inferiority. Overall study success requires that the Cementless group successfully demonstrate non-inferiority when compared to the Control group for all four of the individual primary endpoints. ### B. Accountability of PMA Cohort At the time of database lock, of 378 patients enrolled in the PMA study, 82% (309) patients are available for analysis at the completion of the study, the 24-month post-operative visit. Over the first two years there were 7 deaths and 16 Device removal/reoperations. There were five subjects in the Investigational Group that were originally randomized to receive the Investigational cementless device (Intent-to-Treat population) but due to an intraoperative protocol deviation had the Control cemented device implanted (Per Protocol population) done primarily because of concerns of inadequate device to bone fixation with the cementless subject device. Therefore, in the Cementless Group there are 246 knees in the ITT population and 241 knees in the PP population while the Cemented Group there are 132 knees in the ITT population and 137 knees in the PP population. Details are shown in Figure 2 below. PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 15 of 63 {18} ![img-1.jpeg](img-1.jpeg) Figure 2: Patient Accountability Tree The patient accountability summary by knee is presented for Month 12-, 24-, and 36-month clinical evaluations for the PP (Table 6) and ITT (Table 7) populations. The percentage of patients in each group with complete follow-up data at the 24-month evaluation in the PP population was for All Knees (Investigational: 79%; Control: 79%), Unilateral Knees (Investigational: 81%; Control: 78%), and Bilateral Knees (Investigational: 73%; Control: 82%). The percentage of patients in each group with complete follow-up data at the 24-month evaluation in the ITT population was for All Knees (Investigational: 79%; Control: 79%), Unilateral Knees (Investigational: 81%; Control 77%), and Bilateral Knees (Investigational: 74%; Control: 81%). PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 16 of 63 {19} Table 6: Follow-up Compliance and Subject Accountability for the Per Protocol Population | | Preoperative | | 12 Months | | 24 Months | | 36 Months | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Protocol Window | C | I | C | I | C | I | C | I | | All Knees | | | | | | | | | | Theoretical | 137 | 241 | 137 | 241 | 137 | 241 | 137 | 241 | | Deaths (Cumulative) | 0 | 0 | 2 | 1 | 4 | 1 | 7 | 3 | | Failures (Cumulative) | 0 | 0 | 0 | 11 | 3 | 13 | 4 | 15 | | Expected | 137 | 241 | 132 | 229 | 130 | 227 | 126 | 223 | | Actual^{A} | 137 | 241 | 111 | 203 | 103 | 179 | 78 | 142 | | % Follow-up^{A} | 100.0% | 100.0% | 82.2% | 88.6% | 79.2% | 78.9% | 61.9% | 63.7% | | Actual^{B} | 137 | 241 | 116 | 207 | 114 | 192 | 83 | 161 | | % Follow-up^{B} | 100.0% | 100.0% | 85.9% | 90.4% | 87.7% | 84.6% | 65.9% | 72.2% | | Unilateral | | | | | | | | | | Theoretical | 106 | 199 | 92 | 182 | 90 | 175 | 90 | 173 | | Deaths (Cumulative) | 0 | 0 | 1 | 1 | 2 | 1 | 3 | 1 | | Failures (Cumulative) | 0 | 0 | 0 | 6 | 2 | 7 | 3 | 9 | | Expected | 106 | 199 | 91 | 175 | 86 | 167 | 84 | 163 | | Actual^{A} | 106 | 199 | 78 | 157 | 67 | 135 | 48 | 101 | | % Follow-up^{A} | 100.0% | 100.0% | 85.7% | 89.7% | 77.9% | 80.8% | 57.1% | 62.0% | | Actual^{B} | 106 | 199 | 79 | 159 | 73 | 144 | 52 | 116 | | % Follow-up^{B} | 100.0% | 100.0% | 86.8% | 90.9% | 84.9% | 86.2% | 61.9% | 71.2% | | Bilateral | | | | | | | | | | Theoretical | 31 | 42 | 45 | 59 | 47 | 66 | 47 | 68 | | Deaths (Cumulative) | 0 | 0 | 1 | 0 | 2 | 0 | 4 | 2 | | Failures (Cumulative) | 0 | 0 | 0 | 5 | 1 | 6 | 1 | 6 | | Expected | 31 | 42 | 44 | 54 | 44 | 60 | 42 | 60 | | Actual^{A} | 31 | 42 | 32 | 45 | 36 | 44 | 30 | 41 | | % Follow-up^{A} | 100.0% | 100.0% | 72.7% | 83.3% | 81.8% | 73.3% | 71.4% | 68.3% | | Actual^{B} | 31 | 42 | 36 | 47 | 41 | 48 | 31 | 45 | | % Follow-up^{B} | 100.0% | 100.0% | 81.8% | 87.0% | 93.2% | 80.0% | 73.8% | 75.0% | $^{A}$Patients with complete data for each endpoint in the window time frame $^{B}$Patients with any follow-up data reviewed or evaluated by investigator ("all evaluated" accounting) Failures = Revision or removals of any component of the device or an unanticipated, device-related adverse event I = Investigational Device PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 17 of 63 {20} C = Control Device Table 7: Follow-up Compliance and Subject Accountability for the Intent to Treat Population (ITT Population) | | Preoperative | | 12 Months | | 24 Months | | 36 Months | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Protocol Window | C | I | C | I | C | I | C | I | | All Knees | | | | | | | | | | Theoretical | 132 | 246 | 132 | 246 | 132 | 246 | 132 | 246 | | Deaths (Cumulative) | 0 | 0 | 2 | 1 | 4 | 1 | 7 | 3 | | Failures (Cumulative) | 0 | 0 | 0 | 11 | 2 | 14 | 3 | 16 | | Expected | 132 | 246 | 130 | 234 | 126 | 231 | 122 | 227 | | Actual^{A} | 132 | 246 | 106 | 208 | 99 | 183 | 76 | 144 | | % Follow-up^{A} | 100.0% | 100.0% | 81.5% | 88.9% | 78.6% | 79.2% | 62.3% | 63.4% | | Actual^{B} | 132 | 246 | 111 | 212 | 110 | 196 | 81 | 163 | | % Follow-up^{B} | 100.0% | 100.0% | 85.4% | 90.6% | 87.3% | 84.8% | 66.4% | 71.8% | | Unilateral | | | | | | | | | | Theoretical | 102 | 203 | 88 | 186 | 86 | 179 | 86 | 177 | | Deaths (Cumulative) | 0 | 0 | 1 | 1 | 2 | 1 | 3 | 1 | | Failures (Cumulative) | 0 | 0 | 0 | 6 | 1 | 8 | 2 | 10 | | Expected | 102 | 203 | 87 | 179 | 83 | 170 | 81 | 166 | | Actual^{A} | 102 | 203 | 74 | 161 | 64 | 138 | 46 | 103 | | % Follow-up^{A} | 100.0% | 100.0% | 85.1% | 89.9% | 77.1% | 81.2% | 56.8% | 62.0% | | Actual^{B} | 102 | 203 | 75 | 163 | 70 | 147 | 50 | 118 | | % Follow-up^{B} | 100.0% | 100.0% | 86.2% | 91.1% | 84.3% | 86.5% | 61.7% | 71.1% | | Bilateral | | | | | | | | | | Theoretical | 30 | 43 | 44 | 60 | 46 | 67 | 46 | 69 | | Deaths (Cumulative) | 0 | 0 | 1 | 0 | 2 | 0 | 4 | 2 | | Failures (Cumulative) | 0 | 0 | 0 | 5 | 1 | 6 | 1 | 6 | | Expected | 30 | 43 | 43 | 55 | 43 | 61 | 41 | 61 | | Actual^{A} | 30 | 43 | 31 | 46 | 35 | 45 | 30 | 41 | | % Follow-up^{A} | 100.0% | 100.0% | 72.1% | 83.6% | 81.4% | 73.8% | 73.2% | 67.2% | | Actual^{B} | 30 | 43 | 35 | 48 | 40 | 49 | 31 | 45 | | % Follow-up^{B} | 100.0% | 100.0% | 81.4% | 87.3% | 93.0% | 80.3% | 75.6% | 73.8% | $^{A}$Patients with complete data for each endpoint in the window time frame $^{B}$Patients with any follow-up data reviewed or evaluated by investigator ("all evaluated" accounting) PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 18 of 63 {21} Failures = Revision or removals of any component of the device or an unanticipated, device-related adverse event I = Investigational Device C = Control Device ### **C. Study Population Demographics and Baseline Parameters** The demographics of the study population are typical for a clinical study of subjects undergoing a unicondylar knee arthroplasty performed in the US. Demographic data collected at baseline for the clinical study are presented in the tables below. There are 113 patients (137 knees) for the control and 207 patients (241 knees) for the investigational device. The mean age was 66.4 years for the control and 65.8 years for the investigational. For the control, the gender breakdown was 54% male and 46% women. For the investigational, the gender breakdown was 61.8% male and 38.2% women. The mean BMI for the control was 31.4 and for the investigational was 31.5. The table below summarizes the clinical study demographic by race breakdown. **Table 8: Oxford IDE Demographic by Race** | Outcome | Number of Patients (out of 378) | | --- | --- | | Black or African American | 3 (0.79%) | | Hispanic or Latino | 1 (0.26%) | | White | 277 (73.28%) | | Other | 1 (0.26%) | | Missing or Unknown | 96 (25.40%) | The tables below summarize the patient demographics in the clinical study by treatment. **Table 9: Demographics (Summary/Average by Treatment Group)** | | Control | Investigational | P-Value | | --- | --- | --- | --- | | Number of Knees | 137 | 241 | | | Number of Patients | 113 | 207 | | | At Time of Procedure: | | | | | Age | | | | | N | 137 | 241 | | | mean +/- SD | 66.4 +/- 8.5 | 65.8 +/- 8.7 | 0.5365 | | Range (Min, Max) | (45.0, 81.0) | (37.0, 84.0) | | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 19 of 63 {22} | | Control | Investigational | P-Value | | --- | --- | --- | --- | | Gender | | | | | Male | 54.0% (74/137) | 61.8% (149/241) | 0.1575 | | Female | 46.0% (63/137) | 38.2% (92/241) | | | Height in | | | | | N | 137 | 241 | | | mean +/- SD | 67.5 +/- 3.9 | 67.3 +/- 3.9 | 0.7847 | | Range (Min, Max) | (59.0, 78.0) | (58.0, 76.0) | | | Weight lbs | | | | | N | 137 | 241 | | | mean +/- SD | 204.2 +/- 41.2 | 203.1 +/- 37.0 | 0.7922 | | Range (Min, Max) | (119.0, 320.0) | (127.0, 310.0) | | | BMI | | | | | N | 137 | 241 | | | mean +/- SD | 31.4 +/- 4.8 | 31.5 +/- 5.2 | 0.8791 | | Range (Min, Max) | (21.8, 44.6) | (22.3, 51.0) | | | | Control | Investigational | P-Value | | Preoperative Diagnosis | | | | | Osteoarthritis | 99.3% (136/137) | 97.9% (236/241) | 0.4239 | | Avascular Necrosis | 0.7% (1/137) | 2.1% (5/241) | | | Side of Surgery | | | | | Left | 50.4% (69/137) | 48.1% (116/241) | 0.7482 | | Right | 49.6% (68/137) | 51.9% (125/241) | | | Knee Involvement | | | | | Unilateral | 63.5% (87/137) | 65.1% (157/241) | 0.4606 | | Bilateral (Unilateral Presenting)* | 26.3% (36/137) | 28.2% (68/241) | | | Bilateral (Bilateral Presenting)** | 10.2% (14/137) | 6.6% (16/241) | | *Unilateral Presenting-The subject presented as a unilateral knee and later had the contralateral knee replaced. Note: the contralateral knee may or may not have been enrolled in the study. **Bilateral Presenting- The subject had both knees replaced during the same surgery. PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 20 of 63 {23} **Table 10: Demographics (Category by Treatment Group Overall)** | Patient Demographics – Overall by Treatment (Unilateral and Bilateral) | | | C | I | | --- | --- | --- | --- | --- | | Demographic Measure | Gender | Response | N (%) | N (%) | | **Age** | | | | | | | | <20.0 | 0 | 0 | | | | 20.0-29.9 | 0 | 0 | | | | 30.0-39.9 | 0 | 1(0.4%) | | | | 40.0-49.9 | 6(4.4%) | 10(4.1%) | | | | 50.0-59.9 | 23(16.8%) | 45(18.7%) | | | | 60.0-69.9 | 59(43.1%) | 101(41.9%) | | | | 70.0-79.9 | 46(33.6%) | 73(30.3%) | | | | 80.0-89.9 | 3(2.2%) | 11(4.6%) | | | | 90.0-99.9 | 0 | 0 | | | | >=100.0 | 0 | 0 | | **Height** | | | | | | | **Female** | <60.0 | 2(3.2%) | 3(3.3%) | | | | 60.0-62.9 | 11(17.5%) | 26(28.3%) | | | | 63.0-65.9 | 32(50.8%) | 37(40.2%) | | | | 66.0-68.9 | 17(27.0%) | 23(25.0%) | | | | 69.0-71.9 | 1(1.6%) | 3(3.3%) | | | | 72.0-74.9 | 0 | 0 | | | | 75.0-77.9 | 0 | 0 | | | | >=78.0 | 0 | 0 | | | **Male** | <60.0 | 0 | 1(0.7%) | | | | 60.0-62.9 | 0 | 2(1.3%) | | | | 63.0-65.9 | 3(4.1%) | 10(6.7%) | | | | 66.0-68.9 | 13(17.6%) | 39(26.2%) | | | | 69.0-71.9 | 37(50.0%) | 60(40.3%) | | | | 72.0-74.9 | 19(25.7%) | 33(22.1%) | | | | 75.0-77.9 | 0 | 5(3.4%) | | | | >=78.0 | 2(2.7%) | 0 | | **Operative Difficulty** | | | | | | | | NO | 133(97.1%) | 237(98.3%) | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 21 of 63 {24} | Patient Demographics – Overall by Treatment (Unilateral and Bilateral) | | | C | I | | --- | --- | --- | --- | --- | | Demographic Measure | Gender | Response | N (%) | N (%) | | | | YES | 4(2.9%) | 4(1.7%) | | Gender- Operative Difficulty | | Male | 3 | 2 | | Gender- Operative Difficulty | | Female | 1 | 2 | | Operative Difficulty (Specific) | | | | | | | | LACK OF FEMORAL BONE | 1(0.7%) | 1(0.4%) | | | | OSTEOPOROTIC BONE | 1(0.7%) | 0 | | | | OTHER | 2(1.5%) | 4(1.7%) | | Operative Side | | | | | | | | LEFT | 69(50.4%) | 116(48.1%) | | | | RIGHT | 68(49.6%) | 125(51.9%) | | Weight | | | | | | | Female | <100.0 | 0 | 0 | | | | 100.0-124.9 | 1(1.6%) | 0 | | | | 125.0-149.9 | 5(7.9%) | 15(16.3%) | | | | 150.0-174.9 | 21(33.3%) | 22(23.9%) | | | | 175.0-199.9 | 20(31.7%) | 26(28.3%) | | | | 200.0-224.9 | 9(14.3%) | 16(17.4%) | | | | 225.0-249.9 | 5(7.9%) | 10(10.9%) | | | | 250.0-274.9 | 2(3.2%) | 1(1.1%) | | | | 275.0-299.9 | 0 | 2(2.2%) | | | | >=300 | 0 | 0 | | | Male | <100.0 | 0 | 0 | | | | 100.0-124.9 | 0 | 0 | | | | 125.0-149.9 | 1(1.4%) | 2(1.3%) | | | | 150.0-174.9 | 6(8.1%) | 12(8.1%) | | | | 175.0-199.9 | 20(27.0%) | 42(28.2%) | | | | 200.0-224.9 | 14(18.9%) | 38(25.5%) | | | | 225.0-249.9 | 16(21.6%) | 26(17.4%) | | | | 250.0-274.9 | 6(8.1%) | 23(15.4%) | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 22 of 63 {25} | Patient Demographics – Overall by Treatment (Unilateral and Bilateral) | | | C | I | | --- | --- | --- | --- | --- | | Demographic Measure | Gender | Response | N (%) | N (%) | | | | 275.0-299.9 | 7(9.5%) | 3(2.0%) | | | | >=300 | 4(5.4%) | 3(2.0%) | **Table 11: Demographics (Category by Treatment Group for Bilateral Patients)** | Patient Demographics – Bilateral by Treatment | | | C | I | | --- | --- | --- | --- | --- | | Demographic Measure | Gender | Response | N (%) | N (%) | | **Age** | | | | | | | | <20.0 | 0 | 0 | | | | 20.0-29.9 | 0 | 0 | | | | 30.0-39.9 | 0 | 0 | | | | 40.0-49.9 | 3(6.0%) | 5(6.0%) | | | | 50.0-59.9 | 13(26.0%) | 15(17.9%) | | | | 60.0-69.9 | 20(40.0%) | 35(41.7%) | | | | 70.0-79.9 | 12(24.0%) | 29(34.5%) | | | | 80.0-89.9 | 2(4.0%) | 0 | | | | 90.0-99.9 | 0 | 0 | | | | >=100.0 | 0 | 0 | | **Gender** | | | | | | | | Female | 19(38.0%) | 33(39.3%) | | | | Male | 31(62.0%) | 51(60.7%) | | **Height** | | | | | | | **Female** | <60.0 | 0 | 0 | | | | 60.0-62.9 | 0 | 12(36.4%) | | | | 63.0-65.9 | 7(36.8%) | 13(39.4%) | | | | 66.0-68.9 | 12(63.2%) | 8(24.2%) | | | | 69.0-71.9 | 0 | 0 | | | | 72.0-74.9 | 0 | 0 | | | | 75.0-77.9 | 0 | 0 | | | | >=78.0 | 0 | 0 | | | **Male** | <60.0 | 0 | 0 | | | | 60.0-62.9 | 0 | 0 | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 23 of 63 {26} | Patient Demographics – Bilateral by Treatment | | | C | I | | --- | --- | --- | --- | --- | | Demographic Measure | Gender | Response | N (%) | N (%) | | | | 63.0-65.9 | 2(6.5%) | 4(7.8%) | | | | 66.0-68.9 | 5(16.1%) | 16(31.4%) | | | | 69.0-71.9 | 14(45.2%) | 22(43.1%) | | | | 72.0-74.9 | 10(32.3%) | 9(17.6%) | | | | 75.0-77.9 | 0 | 0 | | | | >=78.0 | 0 | 0 | | **Operative Difficulty** | | | | | | | | NO | 50(100.0%) | 83(98.8%) | | | | YES | 0 | 1(1.2%) | | Gender- Operative Difficulty | Female | | | 1 | | **Operative Difficulty (Specify)** | | | | | | | | OTHER | | 1(1.2%) | | **Operative Side** | | | | | | | | LEFT | 25(50.0%) | 43(51.2%) | | | | RIGHT | 25(50.0%) | 41(48.8%) | | **Weight** | | | | | | | **Female** | <100.0 | 0 | 0 | | | | 100.0-124.9 | 0 | 0 | | | | 125.0-149.9 | 0 | 5(15.2%) | | | | 150.0-174.9 | 4(21.1%) | 9(27.3%) | | | | 175.0-199.9 | 6(31.6%) | 6(18.2%) | | | | 200.0-224.9 | 4(21.1%) | 8(24.2%) | | | | 225.0-249.9 | 5(26.3%) | 5(15.2%) | | | | 250.0-274.9 | 0 | 0 | | | | 275.0-299.9 | 0 | 0 | | | | >=300 | 0 | 0 | | | **Male** | <100.0 | 0 | 0 | | | | 100.0-124.9 | 0 | 0 | | | | 125.0-149.9 | 0 | 0 | | | | 150.0-174.9 | 2(6.5%) | 6(11.8%) | | | | 175.0-199.9 | 10(32.3%) | 8(15.7%) | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 24 of 63 {27} | Patient Demographics – Bilateral by Treatment | | | C | I | | --- | --- | --- | --- | --- | | Demographic Measure | Gender | Response | N (%) | N (%) | | | | 200.0-224.9 | 6(19.4%) | 13(25.5%) | | | | 225.0-249.9 | 5(16.1%) | 11(21.6%) | | | | 250.0-274.9 | 4(12.9%) | 12(23.5%) | | | | 275.0-299.9 | 2(6.5%) | 1(2.0%) | | | | >=300 | 2(6.5%) | 0 | No analyses were performed for sex-, gender-, age-, race-, ethnicity-specific subgroups. #### **D. Safety and Effectiveness Results** ##### **1. Safety Results** The analysis of safety was based on the Investigational and Control study cohorts at 24-months follow-up. In the PP population there were 209 Investigational and 114 Control subjects (knees) while in the ITT population there were 214 Investigational and 109 Control subjects (knees) who were available for the 24-month evaluation. The key safety outcomes for this study are presented below in Tables 12 to 15, 20-27, and 32. Supplementary safety outcomes for this study are presented in Tables 28 to 31 consisting of safety data over the course of the study. Over the course of the study in the PP population there were 241 Investigational and 137 Control subjects (knees) while in the ITT population there were 246 Investigational and 132 Control subjects (knees) who were potentially available for safety data past the 24-month evaluation. Adverse effects are reported in Tables 16 to 19. ##### **Adverse effects that occurred in the PMA clinical study:** ##### **Combined Data (All Knees) Safety Data – 24 Months** A summary of key findings of the 24-month Safety Data concerning the categorization of adverse events (AEs) by device-relatedness and serious/non-serious is provided in Table 12 for the PP and Table 13 for the ITT populations. PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 25 of 63 {28} **Table 12: All Knee-Related Adverse Events (Device-Relatedness and Serious/Non-Serious) (PP) at 24 Months** | Parameter | 24 Months | | | | | --- | --- | --- | --- | --- | | | Investigational (N=209) | Control (N=114) | Relative Risk | 95% CI | | **Adverse Events (AEs) of the index knee** | 198 | 80 | | | | Subjects with AEs of the index knee, n % | 115 (55%) | 46 (40%) | 1.36 | 1.06, 1.76 | | **Device-Related AEs of the index knee** | 45 | 24 | | | | Subjects with device-related AEs of the index knee, n % | 34 (16%) | 12 (11%) | 1.55 | 0.83, 2.87 | | **Total number of AEs of the index knee*, n%** | | | | | | Device Non-Related Non-Serious | 88 (42%) | 38 (33%) | 1.26 | 0.93, 1.71 | | Device Non-Related Serious | 7 (3.3%) | 3 (2.6%) | 1.27 | 0.34, 4.83 | | Device-Related Non-Serious | 28 (13.4%) | 11 (9.6%) | 1.39 | 0.72, 2.68 | | Device-Related Serious | 8 (3.8%) | 3 (2.6%) | 1.45 | 0.39, 5.38 | | All Subjects with Device Revision/Removal | 13 (6.2%) | 3 (2.6%) | 2.36 | 0.69, 8.12 | | All Subjects with Device Removal/Conversion to TKA | 8 (3.8%) | 1 (0.9%) | 4.36 | 0.55, 34.45 | *Each index knee is classified by device-relatedness and serious versus non-serious. Calculations were based on the number of knees in each category. For example, if a case presented with 3 device- non-related non-serious adverse events they were counted once for that category. **Table 13: All Knee-Related Adverse Events (Device-Relatedness and Serious/Non-Serious) (ITT) at 24 Months** | Parameter | 24 Months | | | | | --- | --- | --- | --- | --- | | | Investigational (N=214) | Control (N=109) | Relative Risk | 95% CI | | **Adverse Events (AEs) of the index knee** | 207 | 71 | | | | Subjects with AEs of the index knee, n % | 119 (56%) | 42 (39%) | 1.44 | 1.11, 1.88 | | **Device-Related AEs of the index knee** | 50 | 19 | | | | Subjects with device-related AEs of the index knee, n % | 37 (17%) | 9 (8.3%) | 2.09 | 1.05, 4.18 | | **Total number of AEs of the index knee*, n%** | | | | | | Device Non-Related Non-Serious | 90 (42%) | 36 (33%) | 1.27 | 0.93, 1.74 | | Device Non-Related Serious | 8 (3.7%) | 2 (1.8%) | 2.04 | 0.44, 9.43 | | Device-Related Non-Serious | 31 (14%) | 8 (7.3%) | 1.97 | 0.94, 4.15 | | Device-Related Serious | 9 (4.2%) | 2 (1.8%) | 2.29 | 0.50, 10.42 | | All Subjects with Device Revision/Removal | 14 (6.5%) | 2 (1.8%) | 3.57 | 0.83, 15.41 | | All Subjects with Device Removal/Conversion to TKA | 9 (4.2%) | 0 (0%) | N/A | N/A | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 26 of 63 {29} *Each index knee is classified by device-relatedness and serious versus non-serious. Calculations were based on the number of knees in each category. For example, if a case presented with 3 device- non-related non-serious adverse events they were counted once for that category. In the ITT population the data shows that 37 of 214 knees in the Investigational group (17%) had a device-related adverse event (AE) of the index knee, and 9 of 109 knees in the Control group (8.3%) had a device-related AE involving the index knee (RR 2.09; 95% CI 1.05, 4.18). In the PP population the data show that 34 of 209 knees in the Investigational group (16%) had a device-related adverse event (AE) of the index knee, and 12 of 114 knees in the Control group (11%) had a device-related AE involving the index knee (RR 1.55; 95% CI 0.83, 2.87). In the PP population, the Investigational group compared to the Control group had a clinically but not statistically significant over two-fold risk of sustaining a device revision or removal (RR 2.36; 95% CI 0.69, 8.12) and over four-fold risk of being converted to a total TKA (RR 4.36; 95% CI 0.55, 34.45). The increased relative risk for a knee sustaining a device-related AE was both clinically and statistically significant in the ITT population while it was clinically significant in the PP population. The overall increased rates for a subject to sustain an AE of the index knee in the Investigational versus Control group and the additional failure that required a Subject Device Revision/Removal and conversion to a total knee arthroplasty (TKA) is due to intraoperative protocol deviations. As outlined in the section X.B – Accountability of the PMA Cohort, there were five subjects that were originally randomized to receive the cementless subject investigational device but were instead implanted with the control cemented subject device because of concerns of inadequate device to bone fixation with the cementless subject device. Noteworthy, is that the five subjects that were intraoperative protocol deviations are part of both the PP and ITT population, have a substantial number of AEs to include 4 device non-related non-serious, 1 non-related serious, 4 device-related non-serious, 1 device-related serious and 4 AEs deemed not to require adjudication. Subject PLA1051 was randomized to the Investigational group but the surgeon determined fixation of the tibial component was inadequate and implanted the Control device. PLA1051 was the only device in the Control Group that required a removal of all components and a subsequent total knee arthroplasty because of the onset of rheumatoid arthritis. These five intraoperative protocol deviation patients that were implanted with the control instead of subject device because of concerns of inadequate device to bone fixation should not be only counted as AEs in the subject device group within the PP population because the data does not demonstrate a reasonable assurance of safety and effectiveness to implant a cemented device instead of a cementless device when there is potentially inadequate device to bone-prosthesis fixation. Based on the data from the pivotal IDE Study, when there is concern about the adequacy of the Investigational cementless subject device bone fixation, a TKA should likely be performed instead of a mobile bearing cemented unicondylar knee arthroplasty. Because of the substantial number of AEs and their degree of seriousness in these five subjects that were originally randomized to the subject device but were implanted PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 27 of 63 {30} with the control device, the FDA deems that both the ITT and PP populations should be used to provide the best estimate of the safety of the subject device.$^{3, 4}$ A summary of key findings of the 24-month Safety Data concerning the categorization of AEs by device-relatedness, AE severity, and AE outcome is provided in Table 14 for the PP and Table 15 for the ITT populations. **Table 14: All Knee-Related Adverse Events (AEs) (Severity and AE Outcome) (PP) at 24 Months** | Characteristic | 24 Months | | | --- | --- | --- | | | Based on Knees | | | | Investigational (N=209) | Control (N=114) | | **Total number of AEs of the index knee** | 198 | 80 | | Subjects with AEs of the index knee, n % | 115 (55%) | 46 (40%) | | **Device-Related AEs of the index knee** | 45 | 24 | | Subjects with device-related AEs of the index knee, n % | 34 (16%) | 12 (11%) | | **Adverse Events Severity*, n %** | | | | Mild, number of AEs | 86 (41%) | 36 (32%) | | Moderate, number of AEs | 35 (17%) | 14 (12%) | | Severe, number of AEs | 17 (8.1%) | 6 (5.3%) | | **Device-Related Adverse Events Severity*, n %** | | | | Mild, number of AEs | 22 (11%) | 9 (7.9%) | | Moderate, number of AEs | 8 (3.8%) | 3 (2.6%) | | Severe, number of AEs | 8 (3.8%) | 3 (2.6%) | | **Adverse Events Outcome, n %** | | | | Device Revision/Removal/Reoperation | 15 (7.2%) | 5 (4.4%) | | Study Withdrawal | 0 (0%) | 1 (0.9%) | | Tolerated | 36 (17%) | 16 (14%) | | Not Tolerated | 79 (38%) | 30 (26%) | | Resolved | 53 (25%) | 21 (18%) | | Not Resolved | 62 (30%) | 25 (22%) | | **Device-Related AEs Outcome, n %** | | | | Device Revision/Removal/Reoperation | 8 (3.8%) | 3 (2.6%) | | Study Withdrawal | 0 (0%) | 0 (0%) | | Tolerated | 19 (9.1%) | 8 (7.0%) | | Not Tolerated | 15 (7.2%) | 4 (3.5%) | | Resolved | 6 (2.9%) | 1 (0.9%) | | Not Resolved | 28 (13.4%) | 11 (9.6%) | *Each index knee is classified by adverse event severity and device-related outcomes. Calculations were based on the number of knees in each category. For example, if a case presented with 3 mild adverse events they were counted once for that category. PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 28 of 63 {31} **Table 15: All Knee-Related Adverse Events (AEs) (Severity and AE Outcome) (ITT) at 24 Months** | Characteristic | 24 Months | | | --- | --- | --- | | | Based on Knees | | | | Investigational (N=214) | Control (N=109) | | **Total number of AEs of the index knee** | 207 | 71 | | Subjects with AEs of the index knee, n % | 119 (56%) | 42 (39%) | | **Device-Related AEs of the index knee** | 50 | 19 | | Subjects with device-related AEs of the index knee, n % | 37 (17%) | 9 (8.3%) | | **Adverse Events Severity*, n %** | | | | Mild, number of AEs | 90 (42%) | 32 (29%) | | Moderate, number of AEs | 36 (17%) | 13 (12%) | | Severe, number of AEs | 19 (8.9%) | 4 (3.7%) | | **Device-Related Adverse Events Severity*, n %** | | | | Mild, number of AEs | 25 (12%) | 6 (5.5%) | | Moderate, number of AEs | 8 (3.7%) | 3 (2.8%) | | Severe, number of AEs | 9 (4.2%) | 2 (1.8%) | | **Adverse Events Outcome, n %** | | | | Device Revision/Removal/Reoperation | 17 (7.9%) | 3 (2.8%) | | Study Withdrawal | 0 (0%) | 1 (0.9%) | | Tolerated | 38 (18%) | 14 (13%) | | Not Tolerated | 81 (38%) | 28 (26%) | | Resolved | 53 (25%) | 21 (19%) | | Not Resolved | 66 (31%) | 21 (19%) | | **Device-Related AEs Outcome, n %** | | | | Device Revision/Removal/Reoperation | 9 (4.2%) | 2 (1.8%) | | Study Withdrawal | 0 (0%) | 0 (0%) | | Tolerated | 21 (9.8%) | 6 (5.5%) | | Not Tolerated | 16 (7.5%) | 3 (2.8%) | | Resolved | 6 (2.8%) | 1 (0.9%) | | Not Resolved | 31 (14%) | 8 (7.3%) | *Each index knee is classified by adverse event severity and device-related outcomes. Calculations were based on the number of knees in each category. For example, if a case presented with 3 mild adverse events they were counted once for that category. In the PP population the percentage of device-related AEs in a knee was higher overall and for each severity subgroup in the Investigational group (N=209 [Mild: n=22, (11%); Moderate: n=8 (3.8%); Severe: n=8 (3.8%)] compared to the Control Group (N=114) [Mild: n=9, (7.9%); Moderate: n=3 (2.6%); Severe: n=3 (2.6%)]. In the PP population the percentage of device-related AE outcomes in a knee that were both Tolerated and Not Tolerated was higher in the Investigational group [Tolerated: n=19, (9.1%); Not Tolerated: n=15 (7.2%)] compared to the PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 29 of 63 {32} Control Group [Tolerated: n=8, (7.0%); Not Tolerated: n=4 (3.5%)]. In the PP population the percentage of device-related AE outcomes in a knee that were both Resolved and Not Resolved was higher overall in the Investigational group [Resolved: n=6, (2.9%); Not Resolved: n=28 (13.4%)] compared to the Control Group [Resolved: n=1, 0.9%); Not Resolved: n=11 (9.6%)]. Similar findings were reported in the ITT concerning device-related AEs classification by severity and AE outcomes. A summary of key findings of the 24-month Safety Data concerning the Description of All Knee-Related Adverse Events Description by the Index Knee is provided in Table 16 for the PP and Table 17 for the ITT populations. ---PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 30 of 63 {33} **Table 16: All Knee-Related Adverse Events Description by the Index Knee (PP) at 24 Months** | Adverse Event | 24 Months | | | | | --- | --- | --- | --- | --- | | | Investigational (N=209) | Control (N=114) | Relative Risk | 95% CI | | **Adverse Events (AEs) of the index knee** | 198 | 80 | | | | Subjects with AEs of the index knee, n % | 115 (55%) | 46 (40%) | 1.36 | 1.06, 1.76 | | **Adverse Event Description, n %** | | | | | | Deep Wound Infection | 2 (1.0%) | 0 (0.0%) | N/A | N/A | | Femoral Implant Loosening | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Instability | 6 (2.9%) | 0 (0.0%) | N/A | N/A | | MCL/ACL/PCL/Meniscal Injury | 2 (1.0%) | 1 (0.9%) | 1.09 | 0.10, 11.90 | | Stiffness/Limited ROM (progressive/persistent) | 7 (3.3%) | 3 (2.6%) | 1.27 | 0.34, 4.83 | | Tibial Implant Loosening | 2 (1.0%) | 0 (0.0%) | N/A | N/A | | Tibial Fracture | 4 (1.9%) | 0 (0.0%) | N/A | N/A | | Patellar Subluxation | 0 (0.0%) | 1 (0.9%) | N/A | N/A | | Delayed Wound Healing | 3 (1.4%) | 0 (0.0%) | N/A | N/A | | Hematoma | 6 (2.9%) | 2 (1.8%) | 1.64 | 0.34, 7.98 | | Wound Dehiscence | 4 (1.9%) | 0 (0.0%) | N/A | N/A | | Wound Drainage | 4 (1.9%) | 0 (0.0%) | N/A | N/A | | Superficial Infection | 2 (1.0%) | 1 (0.9%) | 1.09 | 0.10, 11.90 | | Clicking/Popping/Crepitus/Grinding | 11 (5.3%) | 3 (2.6%) | 2 | 0.57, 7.02 | | Pain (progressive/persistent) | 37 (17.7%) | 18 (15.8%) | 1.12 | 0.67, 1.88 | | Subsidence | 2 (1.0%) | 0 (0.0%) | N/A | N/A | | Progressive Disease in Contralateral Compartment | 3 (1.4%) | 3 (2.6%) | 0.55 | 0.11, 2.66 | | Avascular Necrosis | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Bakers Cyst | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Bearing Dislocation/Disassociation | 3 (1.4%) | 1 (0.9%) | 1.64 | 0.17, 15.55 | | Cellulitis/Redness/Blistering | 1 (0.5%) | 1 (0.9%) | 0.55 | 0.03, 8.64 | | Effusion/Swelling/Edema | 28 (13.4%) | 8 (7.0%) | 1.91 | 0.90, 4.05 | | Hemarthrosis/Hemarthritis | 0 (0.0%) | 1 (0.9%) | N/A | N/A | | Synovitis | 3 (1.4%) | 1 (0.9%) | 1.64 | 0.17, 15.55 | | Traumatic Injury (Study Knee) | 9 (4.3%) | 5 (4.4%) | 0.98 | 0.34, 2.86 | | Other Ipsilateral Knee Related AE | 34 (16.3%) | 17 (14.9%) | 1.09 | 0.64, 1.86 | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 31 of 63 {34} **Table 17: All Knee-Related Adverse Events Description by the Index Knee (ITT) at 24 Months** | Adverse Event | 24 Months | | | | | --- | --- | --- | --- | --- | | | Investigational (N=214) | Control (N=109) | Relative Risk | 95% CI | | **Adverse Events (AEs) of the index knee** | 207 | 71 | | | | Subjects with AEs of the index knee, n % | 119 (56%) | 42 (39%) | 1.44 | 1.11, 1.88 | | **Adverse Event Description, n %** | | | | | | Deep Wound Infection | 2 (0.9%) | 0 (0.0%) | N/A | N/A | | Femoral Implant Loosening | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Instability | 6 (2.8%) | 0 (0.0%) | N/A | N/A | | MCL/ACL/PCL/Meniscal Injury | 2 (0.9%) | 1 (0.9%) | 1.02 | 0.09, 11.11 | | Stiffness/Limited ROM (progressive/persistent) | 8 (3.7%) | 2 (1.8%) | 2.04 | 0.44, 9.43 | | Tibial Implant Loosening | 2 (0.9%) | 0 (0.0%) | N/A | N/A | | Tibial Fracture | 4 (1.9%) | 0 (0.0%) | N/A | N/A | | Patellar Subluxation | 0 (0.0%) | 1 (0.9%) | N/A | N/A | | Delayed Wound Healing | 3 (1.4%) | 0 (0.0%) | N/A | N/A | | Hematoma | 6 (2.8%) | 2 (1.8%) | 1.53 | 0.31, 7.45 | | Wound Dehiscence | 4 (1.9%) | 0 (0.0%) | N/A | N/A | | Wound Drainage | 4 (1.9%) | 0 (0.0%) | N/A | N/A | | Superficial Infection | 2 (0.9%) | 1 (0.9%) | 1.02 | 0.09, 11.11 | | Clicking/Popping/Crepitus/Grinding | 12 (5.6%) | 2 (1.8%) | 3.06 | 0.70, 13.41 | | Pain (progressive/persistent) | 39 (18.2%) | 16 (14.7%) | 1.24 | 0.73, 2.12 | | Subsidence | 2 (0.9%) | 0 (0.0%) | N/A | N/A | | Progressive Disease in Contralateral Compartment | 4 (1.9%) | 2 (1.8%) | 1.02 | 0.19, 5.47 | | Avascular Necrosis | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Bakers Cyst | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Bearing Dislocation/Disassociation | 3 (1.4%) | 1 (0.9%) | 1.53 | 0.16, 14.52 | | Cellulitis/Redness/Blistering | 1 (0.5%) | 1 (0.9%) | 0.51 | 0.03, 8.07 | | Effusion/Swelling/Edema | 29 (13.6%) | 7 (6.4%) | 2.11 | 0.96, 4.66 | | Hemarthrosis/Hemarthritis | 0 (0.0%) | 1 (0.9%) | N/A | N/A | | Synovitis | 3 (1.4%) | 1 (0.9%) | 1.53 | 0.16, 14.52 | | Traumatic Injury (Study Knee) | 10 (4.7%) | 4 (3.7%) | 1.27 | 0.41, 3.97 | | Other Ipsilateral Knee Related AE | 35 (16.4%) | 16 (14.7%) | 1.11 | 0.65, 1.92 | When examining the Description of All Knee-Related Adverse Events by the Index Knee, both the PP and ITT populations had several adverse event types with increased incidence rates in the Investigational compared to the Control group. Higher noteworthy incidence rates in the Investigational compared to the Control group were reported for femoral implant loosening, instability, stiffness/limited range of motion, tibial implant loosening, tibial fracture, delayed PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 32 of 63 {35} wound healing, hematoma, wound dehiscence, wound drainage, clicking/popping/crepitus/grinding, pain, subsidence, avascular necrosis, bearing dislocation/disassociation, effusion/swelling/edema, synovitis, deep wound infection, and other ipsilateral Knee Related AE. In summary, the relative risk of the Investigational Group compared to Control Group for AEs of the index knees is 1.44 with a 95% confidence interval (CI) (1.11, 1.88) in the ITT and 1.36 with 95% CI (1.06, 1.76) in the PP populations that is both clinically and statistically significant. A summary of key findings of the 24-month Safety Data concerning the Description of All Knee-Related and Device-Related Adverse Events by the Index Knee is provided in Table 18 for the PP and Table 19 for the ITT populations. **Table 18: All Knee-Related and Device-Related Adverse Events Description by the Index Knee (PP) at 24 Months** | Adverse Event | 24 Months | | | | | --- | --- | --- | --- | --- | | | Investigational (N=209) | Control (N=114) | Relative Risk | 95% CI | | **Device-Related AEs of the index knee** | 45 | 24 | | | | Subjects with device-related AEs of the index knee, n % | 34 (16%) | 12 (11%) | 1.55 | 0.83, 2.87 | | **Adverse Event Description, n %** | | | | | | Femoral Implant Loosening | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Instability | 2 (1.0%) | 0 (0.0%) | N/A | N/A | | Stiffness/Limited ROM (progressive/persistent) | 2 (1.0%) | 1 (0.9%) | 1.09 | 0.10, 11.90 | | Tibial Implant Loosening | 2 (1.0%) | 0 (0.0%) | N/A | N/A | | Tibial Fracture | 2 (1.0%) | 0 (0.0%) | N/A | N/A | | Patellar Subluxation | 0 (0.0%) | 1 (0.9%) | N/A | N/A | | Clicking/Popping/Crepitus/Grinding | 2 (1.0%) | 2 (1.8%) | 0.55 | 0.08, 3.82 | | Pain (progressive/persistent) | 5 (2.4%) | 4 (3.5%) | 0.68 | 0.19, 2.49 | | Subsidence | 2 (1.0%) | 0 (0.0%) | N/A | N/A | | Progressive Disease in Contralateral Compartment | 0 (0.0%) | 1 (0.9%) | N/A | N/A | | Avascular Necrosis | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Bearing Dislocation/Disassociation | 3 (1.4%) | 1 (0.9%) | 1.64 | 0.17, 15.55 | | Effusion/Swelling/Edema | 5 (2.4%) | 4 (3.5%) | 0.68 | 0.19, 2.49 | | Hemarthrosis/Hemarthritis | 0 (0.0%) | 1 (0.9%) | N/A | N/A | | Other Ipsilateral Knee Related AE | 13 (6.2%) | 3 (2.6%) | 2.36 | 0.69, 8.12 | PMA P010014/S105: FDA Summary of Safety and Effectiveness Data 33 of 63 {36} **Table 19: All Knee-Related and Device-Related Adverse Events Description by the Index Knee (ITT) at 24 Months** | Adverse Event | 24 Months | | | | | --- | --- | --- | --- | --- | | | Investigational (N=214) | Control (N=109) | Relative Risk | 95% CI | | **Device-Related AEs of the index knee** | 50 | 19 | | | | Subjects with device-related AEs of the index knee, n % | 37 (17%) | 9 (8.3%) | 2.09 | 1.05, 4.18 | | **Adverse Event Description, n %** | | | | | | Femoral Implant Loosening | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Instability | 2 (0.9%) | 0 (0.0%) | N/A | N/A | | Stiffness/Limited ROM (progressive/persistent) | 3 (1.4%) | 0 (0.0%) | N/A | N/A | | Tibial Implant Loosening | 2 (0.9%) | 0 (0.0%) | N/A | N/A | | Tibial Fracture | 2 (0.9%) | 0 (0.0%) | N/A | N/A | | Patellar Subluxation | 0 (0.0%) | 1 (0.9%) | N/A | N/A | | Clicking/Popping/Crepitus/Grinding | 3 (1.4%) | 1 (0.9%) | 1.53 | 0.16, 14.52 | | Pain (progressive/persistent) | 6 (2.8%) | 3 (2.8%) | 1.02 | 0.26, 4.00 | | Subsidence | 2 (0.9%) | 0 (0.0%) | N/A | N/A | | Progressive Disease in Contralateral Compartment | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Avascular Necrosis | 1 (0.5%) | 0 (0.0%) | N/A | N/A | | Bearing Dislocation/Disassociation | 3 (1.4%) | 1 (0.9%) | 1.53 | 0.16, 14.52 | | Effusion/Swelling/Edema | 6 (2.8%) | 3 (2.8%) | 1.02 | 0.26, 4.00 | | Hemarthrosis/Hemarthritis | 0 (0.0%) | 1 (0.9%) | N/A | N/A | | Other Ipsilateral Knee Related AE | 13 (6.1%) | 3 (2.8%) | 2.21 | 0.64, 7.58 | When examining the Description of All Knee-Related and Device-Related Adverse Events by the Index Knee, both the PP and ITT populations had several adverse event types with increased incidence rates in the Investigational compared to the Control group. Higher noteworthy incidence rates in the Investigational compared to the Control group were reported for femoral implant loosening, instability, stiffness/limited range of motion, tibial implant loosening, tibial fracture, subsidence, avascular necrosis, bearing dislocation/disassociation, and other ipsilateral Knee Related AE. Among patients categorized with the adverse event description Other Ipsilateral Knee Related… --- **Source:** [https://fda-staging.innolitics.com/device/P010014S105](https://fda-staging.innolitics.com/device/P010014S105) **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. 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