Naproxcinod Relieves Osteoarthritis Hip Pain as Well as Naproxen, With Better Safety Profile: Presented at ACR/ARHP
ATLANTA -- November 10, 2010 -- Naproxcinod, the first cyclooxygenase inhibiting nitric oxide donator (CINOD) in development for the treatment of osteoarthritis, was found comparable to naproxen in its ability to relieve the pain of hip osteoarthritis, while causing fewer adverse effects on blood pressure, researchers stated here at the 2010 Annual Scientific Meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP).
Naproxcinod was found to be statistically superior to placebo (P <.0001) at all times for 3 coprimary endpoints in this study: change from baseline in two different Western Ontario and McMaster Universities Osteoarthritis Index subscales (pain and physical function), as well as patients' overall rating of disease status (5-point Likert scale) after 13 weeks. A post hoc analysis also demonstrated that naproxcinod was noninferior to naproxen on these endpoints, noted Christoph G. Baerwald, MD, Universitätsklinikum, Leipzig, Germany, and colleagues, reporting here on November 9.
In all, 810 eligible patients were randomised at baseline to receive either naproxcinod 750 mg twice daily, placebo twice daily, or naproxen 500 mg twice daily (a dose that is equimolar to naproxcinod 750 mg twice daily) in a 2:2:1 ratio, respectively.
Of the randomised patients, 191 (23.6%) discontinued the study prematurely. Discontinuations due to lack of efficacy occurred in 11.5% of the placebo group, 6.2% of the naproxcinod group, and 3.2% of the naproxen group. Discontinuations due to adverse events occurred in 5.7% of the placebo group, 6.5% in the naproxcinod group, and 9% in the naproxen group.
The safety assessment was mainly based on seated office blood pressure measurement, (performed between 2 and 4 hours post dose of study medication) and monitoring for adverse events.
Naproxcinod was found to be well tolerated. The proportion of patients reporting at least 1 adverse event was 46.8% in the naproxen group, 43.2% in the naproxcinod group, and 38.2% in the placebo group; the proportion in each group reporting treatment-related adverse events was 22.4%, 19.6%, and 14.8%, respectively. The most commonly reported adverse events were gastrointestinal disorders, and most adverse events were mild or moderate.
Naproxcinod was also found to have a blood pressure profile that tended to be different from that of naproxen. The mean change from baseline at week 13 in systolic blood pressure was -2.60 +- 11.33 mm Hg in the naproxcinod 750 mg twice-daily group, -2.49 +- 11.64 mm Hg in the placebo twice-daily group, and -0.49 +- 12.32 mm Hg in the naproxen 500 mg twice-daily group. Increases in systolic blood pressure over 10 mm Hg at week 13 compared with baseline were reported in 20.3% of naproxen patients, 13.3% of naproxcinod patients, and 15.0% of placebo patients.
Subjects had a mean age of 63.0 years, and 41.9% were over 65 years old. Overall, 65.6% were female and 50.5% were hypertensive.
Funding for this study was provided by NicOx S.A.
[Presentation title: 13-Week Efficacy and Safety Evaluation of Naproxcinod, a Cyclooxygenase Inhibiting Nitric Oxide Donator (CINOD), in Patients With Osteoarthritis of the Hip. Abstract 936]