1er ABSTRACT à l'EULAR
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FRI0464 13-WEEK EFFICACY AND SAFETY EVALUATION OF NAPROXCINOD, A FIRST-IN-CLASS CYCLOOXYGENASE INHIBITING NITRIC OXIDE DONATOR (CINOD), IN PATIENTS WITH OSTEOARTHRITIS OF THE HIP
C. G. Baerwald 1,*, H. Frayssinet 2, T. Ferreira 2, B. Duquesroix 2, T. Schnitzer 3
1Klinik fur Gastroenterologie und Rheumatologie, Universitatskinlinikum Leipzig, Leipzig, Germany, 2NicOx, SA, Sophia Antipolis, France, 3Northwestern University, Chicago, United States
da notare;
il campione studio 303 (13 settimane per artrosi all'anca) è composto per il 97% da caucasi, per cui suppongo che sia stato elaborato in ex urss
non si parla di non inferiorità di efficacia rispetto a naproxene ma di efficacia simile al naproxene..
Background: Naproxcinod is a first-in-class Cyclooxygenase Inhibiting Nitric Oxide Donator (CINOD) under development for the relief of signs and symptoms of osteoarthritis (OA). Naproxcinod has demonstrated anti-inflammatory and analgesic properties similar to traditional NSAIDs and COX-2 inhibitors. It has shown a good safety profile in previous trials in knee OA so it was evaluated in this study in OA of the hip.
Objectives: The primary objective of this study was to demonstrate that naproxcinod 750 mg bid was superior to placebo bid in relieving OA signs and symptoms in patients with OA of the hip. The secondary objectives were to evaluate the effect on blood pressure (BP) of naproxcinod 750 mg bid, vs. placebo bid and naproxen 500 mg bid, as measured by Office Blood Pressure Monitoring (OBPM); and to evaluate the general safety and tolerability of naproxcinod 750 mg bid vs. placebo bid and naproxen 500 mg bid.
Methods: 810 patients with primary hip OA experiencing pain flare at baseline after discontinuation of previous analgesic treatment were randomized at 105 European and North American centers to naproxcinod 750mg, placebo or naproxen 500mg (all bid) in a 2:2:1 ratio. Efficacy was assessed using 3 co-primary endpoints: change from baseline in WOMAC™ pain and function subscales, and patients’ overall rating of disease status at Week 13. Several secondary efficacy assessments were also performed. The primary efficacy variables were analyzed using an ANCOVA model with treatment group and site as factors, and the appropriate baseline value as a covariate. Safety was assessed by adverse events (AEs), standardized BP monitoring, ECGs, laboratory assessments, and physical examinations.
Results: 810 patients were randomized (ITT population): 65.6% female, 97% Caucasian, mean age 63 years. 50.5% of patients were hypertensive, 13.6% were diabetic and 19.5% used low dose aspirin. Overall, 23.6% of patients discontinued from the study prematurely, primarily due to lack of efficacy (7.8%), with most patients being in the placebo group. Naproxcinod 750mg demonstrated statistically significant superiority over placebo for all 3 co-primary efficacy variables at all time points (p<0.0001). Results seen in the naproxen group were similar to those in the naproxcinod group. Treatments were well tolerated. At least one AE was reported in 43.2% patients in the naproxcinod 750mg group, 38.2% in the placebo group and 46.8% in the naproxen 500mg group. Most AEs were mild or moderate in severity, and the incidence of SAEs was low and similar among treatment groups (1.5% to 2.6%). The BP profile was similar in the naproxcinod and placebo groups, while patients on naproxen showed a BP increase relative to placebo.
Conclusion: Naproxcinod was statistically superior to placebo during 13 weeks of treatment in relieving the signs and symptoms of OA of the hip, as evidenced by all 3 co-primary efficacy variables. These results reflect those seen in other Phase 3 studies and demonstrate a clinical benefit following naproxcinod treatment in the more difficult indication of OA of the hip. Naproxcinod was well tolerated with a BP profile similar to placebo, while naproxen increased BP compared to placebo.
Disclosure of Interest: C. Baerwald: None Declared, H. Frayssinet Employee of: NicOx SA, Sophia Antipolis, France, T. Ferreira Employee of: NicOx SA, Sophia Antipolis, France, B. Duquesroix Employee of: NicOx SA, Sophia Antipolis, France, T. Schnitzer Shareholder of: NicOx SA, Sophia Antipolis, France, Consultant for: NicOx SA, Sophia Antipolis, France