NicOx SA, of Sophia Antipolis, France, announced early completion of accrual for the first phase III trial of HCT 3012, a novel, proprietary, nitric oxide-donating derivative of naproxen. NicOx intends to develop HCT 3012 as the drug of choice for osteoarthritis (OA) patients, particularly those with coexisting hypertension, a key cardiovascular risk in up to 40% of the OA population. The randomization of 820 patients with OA of the knee at 120 clinical sites in the US was initiated in late December 2005 and has been completed ahead of the projected timelines. Results are anticipated in the fourth quarter of 2006.

The phase III trial is designed to demonstrate that HCT 3012 is superior to placebo and as effective as naproxen in relieving the signs and symptoms of OA, in addition to showing that HCT 3012 has no detrimental effect on blood pressure, unlike all other nonsteroidal anti-inflammatory drugs (NSAIDs). An additional trial was recently initiated, using ambulatory blood pressure monitoring (ABPM) to compare the 24-hour blood pressure profile of HCT 3012 and naproxen in hypertensive subjects.

The phase III study is a 13-week, double-blind, placebo- and naproxen-controlled trial. Eligible patients were randomized to one of four treatment groups: HCT 3012 375 mg bid, HCT 3012 750 mg bid, naproxen 500 mg bid, or placebo bid, with approximately 205 patients enrolled per treatment group. HCT 3012 and placebo will be compared on three co-primary endpoints, based on the mean change between baseline and week 13 in the following scores: the WOMACâ„¢ pain subscale, the WOMAC function subscale, and patients' overall rating of disease status, which are the standard endpoints used to demonstrate the efficacy of a drug for treating the signs and symptoms of OA. A noninferiority comparison of HCT 3012 and naproxen will be a secondary endpoint of the study.

—A. Techman