Efficacy and safety of naproxcinod in the treatment of patients with osteoarthritis of the knee: A 13-week prospective, randomized, multicenter study

Objective: To evaluate the efficacy and safety of the cyclooxygenase-inhibiting nitric-oxide donator, naproxcinod, compared with naproxen and placebo in patients with osteoarthritis (OA) of the knee. Method: 918 eligible patients were randomly assigned to double-blind treatment with either naproxcinod 375. mg, naproxcinod 750. mg, naproxen 500. mg or placebo, twice daily for 13 weeks. The primary objective was to show superiority of naproxcinod compared to placebo. Main efficacy criteria were assessment of pain and physical function using the Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC^™) and patients' overall rating of disease status (Likert scale). The main secondary objectives were to show that naproxcinod was non-inferior to naproxen 500. mg and to evaluate overall safety. Results: Both doses of naproxcinod were statistically and clinically superior to placebo in relieving signs and symptoms of OA of the knee after 13 weeks of treatment, as demonstrated by all three co-primary endpoints (P≤0.0003). The evaluation of the other secondary efficacy measures was consistent with the primary endpoint results. Naproxcinod 750. mg was non-inferior to equimolar doses of naproxen 500. mg in the Intent-to-Treat (ITT) population. 24.5% of patients discontinued prematurely, with a higher incidence in the placebo group (18.6%) than the active groups (4.3-7.1%) discontinuing due to lack of efficacy. Both doses of naproxcinod were well-tolerated, with most adverse events being mild or moderate. Compared to placebo, naproxcinod 750. mg and 375. mg showed a similar blood pressure (BP) profile in contrast to naproxen which increased BP. Conclusions: These results demonstrated the clinical efficacy and safety of naproxcinod in the management of the signs and symptoms of OA. Naproxcinod was well-tolerated, with BP effects similar to placebo and different from naproxen.Clinical Trials.gov identifier: NCT00542555.