Résumé de l'intervention au Congrès de Boston

Title:

Efficacy and Safety of Naproxcinod Compared to Placebo and Naproxen in Patients with Osteoarthritis of the Knee: Results from a 13-Week Randomized Double-Blind Trial
Category:

7. Osteoarthritis - clinical aspects
Author(s):

Thomas Schnitzer1, Alan Kivitz2, Bruce Rankin3, Chester Fisher4, Richard Fishman5, Howard Marker6, Hayet Frayssinet7, Brigitte Duquesroix7. 1Northwestern University, Chicago, IL; 2Altoona Center for Clinical Research, Duncansville, PA; 3University Clinical Research Deland, Deland, FL; 4Health Research of Hampton Roads, Newport News, VA; 5Palm Beach Research Center, Pico Rivera, CA; 6Sarah Cannon Research Institute, LLC, Memphis, TN; 7NicOx, Sophia-Antipolis, France
Presentation Number:

1678
Poster Board Number:

292
Abstract:

PURPOSE: Naproxcinod is a first-in-class Cyclooxygenase Inhibiting Nitric Oxide Donator (CINOD) with anti-inflammatory and analgesic properties. Naproxcinod exerts its therapeutic effects by inhibiting both COX-1 and COX-2 enzymes which leads to reduced prostaglandin formation. In addition, by releasing nitric oxide (NO), naproxcinod has a blood pressure (BP) lowering effect and counteracts the detrimental effects of prostaglandin deficiency in the gastrointestinal tract. The objective of this first phase 3 study was to assess the efficacy and safety of naproxcinod in comparison to placebo and naproxen, in treating the signs and symptoms of osteoarthritis (OA) and to evaluate its effect on BP.

METHODS: A total of 918 knee OA patients were randomized to either naproxcinod 750 mg bid, naproxcinod 375 mg bid, naproxen 500 mg bid, or placebo bid. To be eligible, patients were to be >= 40 years of age, meet ACR criteria for knee OA, and demonstrate a flare on washout of current medications.
RESULTS: Both doses of naproxcinod were superior to placebo in the three co-primary endpoints of WOMACTM pain and function, and subject’s overall rating of disease status at Week 13 (least squares mean difference [95% confidence interval] -12 mm [-17, -7], -12 mm [-17, -7], 0.6 [0.4, 0.8] respectively for 750 mg bid dose (P < 0.0001); and -10 mm [-14, -5], -9 mm [-14, -4], 0.5 [0.3, 0.7] respectively for 375 mg bid dose (p <= 0.0002)). Overall, both doses of naproxcinod were safe with respectively 46.7% and 40.8% of patients with at least one AE in the highest and lowest doses, as compared to 56.4% and 38.7% in the naproxen 500 mg bid and placebo groups. Naproxcinod showed a favourable and sustained BP effect over the study. At Week 13, naproxcinod 750 mg bid and 375 mg bid showed slight decreases in mean change from baseline in systolic BP (SBP) vs. placebo (0.8 and 0.2 mmHg respectively) while a 2 mmHg increase was observed in naproxen vs. placebo.

CONCLUSION: Both dosages of naproxcinod demonstrated superior efficacy to placebo and similar efficacy to that of an equimolar dose of naproxen. There were no general safety concerns. Both naproxcinod groups had SBP profiles comparable to placebo and better than naproxen. Naproxcinod offers a promising clinical and pharmacological profile for the treatment of OA patients.

Source : American College of Rheumatology