NicOx SA, a French biopharmaceutical company focused on the development of nitric-oxide-donating drugs to treat inflammation, pain, and cardio-metabolic disease, announced the start of the first phase III trial for HCT 3012, a nitric-oxide-donating derivative of naproxen (CINOD, or cyclooxygenase [COX]-inhibiting nitric-oxide donator), in patients with osteoarthritis (OA) of the knee.

The US trial, involving approximately 120 clinical study sites and 820 patients, is a 13-week, double-blind, placebo-and naproxen-controlled study designed to test whether HCT 3012 is superior to placebo and as effective as naproxen in relieving the signs and symptoms of OA without a detrimental effect on blood pressure. The results of the study are expected to be announced near the end of 2006.

An additional trial, scheduled to begin in the second quarter of 2006, will employ ambulatory blood pressure monitoring to compare the blood pressure profile of HCT 3012 and naproxen over a 24-hour period in hypertensive patients. According to NicOx, approximately 40% of OA patients are estimated to have hypertension.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors can cause a rise in arterial blood pressure, which may contribute to the increase in cardiovascular events associated with these drugs. HCT 3012, through nitric-oxide-donation, may potentially counteract the detrimental effects of COX inhibition on blood pressure and prove beneficial in patients with OA and concomitant cardiovascular risk factors. NicOx also believes that nitric-oxide-donation may improve the gastrointestinal and renal safety profile of HCT 3012, compared with existing NSAIDs.

In successful phase II trials in more than 3000 patients, HCT 3012 demonstrated equal efficacy to existing NSAID and COX-2 inhibitors, together with improved gastric safety and tolerability, compared to naproxen. Of significance were the findings on blood pressure, where the COX-2 inhibitor rofecoxib showed an increase in systolic blood pressure, an effect particularly evident in hypertensive patients, while HCT 3012 demonstrated no statistically significant difference compared to placebo.

NicOx has also reported positive results from a pilot phase II study for HCT 1026, a nitric-oxide-donating derivative of flurbiprofen, for the treatment of osteopenia. The trial found that treatment with HCT 1026 resulted in a clinical response (the primary endpoint) in 24% of patients and a significant reduction in bone resorption markers. HCT 1026 is also in clinical development for the treatment of Alzheimer's disease.

―A. Techman