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Topical Ointment for OA Knee Pain Flunks Mid-Stage Trial
Disappointing results have been reported from a double-blind, placebo-controlled, phase IIb study designed to evaluate the safety and efficacy of topically applied TV-45070 (4% and 8% w/w ointment, Teva Pharmaceutical Industries/ Xenon Pharmaceuticals) in patients with chronic pain due to osteoarthritis (OA) of the knee.
TV-45070 is a small-molecule inhibitor of the Nav1.7 sodium channel and other sodium channels, including those that are expressed in the pain-sensing peripheral nervous system.
In this study, TV-45070 4% and 8% did not demonstrate a statistically significant difference from placebo in efficacy endpoints of reductions in pain due to OA.
TV-45070 did have a favorable safety and tolerability profile, with no drug-related serious adverse events. The most common adverse events were application-site skin reactions, which were mostly mild. There were no cardiac or CNS safety issues.
Applied topically, TV-45070 acts locally to inhibit Nav1.7 in the skin and underlying tissue, mitigating systemic absorption and the potential risks of adverse effects that accompany systemic drug metabolism. A phase IIb trial of TV-45070 in patients with post-herpetic neuralgia is under way, with results expected in the second half of 2016.
The phase IIb study of TV-45070 in OA patients was a randomized, double-blind, placebo-controlled trial conducted at approximately 40 clinical sites in the US. A total of 389 patients were randomly assigned to receive TV-45070 4% administered twice per day; TV-45070 8% administered twice per day; or a placebo comparator (a matched ointment without TV-45070) administered twice per day. The patients were eligible to participate in the trial if they were 40 to 85 years of age, had primary OA in a single knee (the target knee), met pre-specified visual analog scale (VAS) pain scores, and were otherwise medically healthy.
The study’s primary endpoint was the efficacy of 4 weeks of topical administration of TV-45070 (4% and 8% ointment) compared with placebo for the relief of symptoms of primary OA of the target knee, as assessed by the change from baseline to the last 5 days of treatment in the average evening pain score upon walking on a flat surface, using question 1 of the Western Ontario and McMasters Universities Arthritis Index (WOMAC) on a 0- to 100-mm visual analog scale. Efficacy endpoints were analyzed in all patients who received at least one dose of study drug and at least one post-baseline efficacy assessment. Key secondary objectives of the trial included changes in the WOMAC pain subscale scores, responder rates, and patient-reported outcome assessments.
Source: Xenon Pharmaceuticals; July 1, 2015.