NicOx Launches Second Phase III Study of Naproxcinod

NicOx announced that it has initiated the second pivotal Phase III trial (study 302) for naproxcinod in patients with osteoarthritis of the knee. The trial is expected to enroll approximately 1,020 patients at 120 clinical centers in the U.S. The objective of the study is to confirm naproxcinod's efficacy and provide additional blood pressure data, a key factor to differentiate naproxcinod from existing treatments. Efficacy results are expected in mid-2008.

Naproxcinod is the first compound in the Cox-inhibiting nitric oxide-donating class, which NicOx aims to develop as the drug-of-choice for treating the signs and symptoms of osteoarthritis. The initiation of 302 follows the successful results obtained for naproxcinod in previous Phase II and III trials, which showed superior efficacy to placebo and no detrimental effect on blood pressure compared with existing non-steroidal anti-inflammatory drugs.

The 302 study is a 53-week, randomized, double-blind, efficacy and safety trial in patients with osteoarthritis of the knee. Eligible patients will be randomized to one of the following treatment groups: naproxcinod 375 mg twice a day, naproxcinod 750 mg twice a day, naproxen 500 mg twice a day and placebo twice a day during the first 13 weeks. After 13 weeks, the placebo-treated patients will be randomized to either naproxcinod 375 mg or naproxcinod 750 mg for the remainder of the trial (39 weeks).

The two doses of naproxcinod will be compared with placebo on three co-primary efficacy endpoints, based on the mean change between baseline and week 13 in the following scores: the Western Ontario and McMaster Osteoarthritis (WOMAC) pain subscale, the WOMAC function subscale and subjects' overall rating of disease status.

A secondary endpoint of the trial will compare the efficacy of naproxcinod and naproxen at 26 weeks. The general safety and tolerability of naproxcinod will be assessed until week 52, and the trial will have a one-week post-treatment safety period.

As in the 301 study, patients' blood pressure will be assessed during each visit to the treatment center, using controlled office blood pressure measurements. The blood pressure effect of naproxcinod will be assessed in two groups of patients: the overall population and a subgroup of hypertensive subjects. Various blood pressure endpoints will compare the different treatments in terms of the mean change from baseline in systolic and diastolic blood pressure at a range of time points. Additional blood pressure endpoints will assess the appearance of new hypertension or worsening of preexisting hypertension.

NicOx plans to initiate a third Phase III trial (the 303 study) to assess naproxcinod's efficacy and safety in patients with osteoarthritis of the hip. In addition, the company will conduct a predefined statistical analysis on the pooled blood pressure data from the three studies.