A RANDOMIZED, PARALLEL GROUP, DOUBLE BLIND, PLACEBO AND NAPROXEN CONTROLLED, MULTICENTER PHASE 3 STUDY OF NAPROXCINOD IN SUBJECTS WITH OSTEOARTHRITIS OF THE KNEE: EFFICACY RESULTS FOLLOWING 13-WEEK TREATMENT

Background: Naproxcinod is a Cycloxygenase Inhibiting Nitric Oxide Donator (CINOD) under development for the relief of signs and symptoms of OA. In previous trials naproxcinod has shown anti-inflammatory and analgesic properties similar to traditional NSAIDs and COX2 inhibitors associated with a favorable safety and tolerability profile. Objectives: The primary objective of the study was to show that naproxcinod 375 mg bid and 750 mg bid were superior to placebo in relieving signs and symptoms in subjects with OA of the knee at Week 13. Methods: Subjects (40+ years of age) meeting ACR criteria for knee OA and experiencing a flare of pain at baseline after discontinuation of previous analgesic treatment were randomized (1:1:1:1) to either naproxcinod 375 mg or 750 mg bid, naproxen 500 mg bid or placebo bid. The three co-primary efficacy variables were the mean change from Baseline to Week 13 in WOMAC™ pain and function subscale scores and subject's global assessment of disease status to compare naproxcinod with placebo for superiority. The analysis of each primary efficacy variable was based on an analysis of covariance (ANCOVA) model with treatment group and center as factors, and baseline value as covariate. The primary efficacy analysis was performed using the Intent-to-Treat (ITT) population and was performed on as-randomized basis. Results: The ITT population consisted of 1011 subjects from 129 centers in the US. 71.0% of subjects were female, 78.9% Caucasian; mean age was 59.8 years, mean BMI 33.8 kg/m2. At Week 13, 766 subjects completed the study (75.8%). Both doses of naproxcinod (375 mg bid and 750 mg bid) demonstrated superior efficacy to placebo in the three co-primary endpoints of WOMAC™ pain and function, and subject's overall rating of disease status (p≤0.0004). In addition, naproxcinod 750 mg bid was non-inferior to naproxen 500 mg bid. Percent of subjects with at least 1 AE was 47.0%, 46.4%, for naproxcinod 375 and 750 mg bid, respectively, 47.7% for naproxen and 44.8% for placebo. Conclusion: This study demonstrated the clinical efficacy of both naproxcinod doses over placebo, confirming the results of previous trials. Treatments were safe and well tolerated. References: 1. Study HCT 3012-X-302. First 13 weeks of treatment. Disclosure of Interest: CEM, CT, TS, VA, JA, DH were investigators in this NicOx' sponsored study. JS, HF, DB are Nicox' employees.Citation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 285Session: Osteoarthritis (Poster Presentations )