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Multiple Sclerosis Drug Fails Phase III Trial
A pivotal phase III study of arbaclofen placarbil (AP; XenoPort, Inc.) for the treatment of patients with spasticity due to multiple sclerosis was unsuccessful in demonstrating that the drug provided statistically significant improvement compared with placebo in the trial’s co-primary endpoints.
The 13-week, randomized, double-blind, placebo-controlled study enrolled 228 subjects in the U.S. The trial consisted of a 1-week placebo run-in period, 2 weeks of up-titration, 8 weeks at the maintenance dose, and 2 weeks of down-titration. The subjects were randomly assigned to one of four treatment arms: AP 15 mg, AP 30 mg, AP 45 mg, or placebo administered twice a day with food.
The first of the study’s co-primary endpoints was the time-matched change from baseline in the Maximum Ashworth score (6 hours post-dose time point) at the end of the maintenance period. The muscle group in the lower limbs with the highest Ashworth score at baseline was followed throughout the trial. Subjects entering the trial were required to have a Maximum Ashworth score of 2 or greater before entering the study and at the end of the placebo run-in period, which served as the baseline.
The study’s second co-primary endpoint was the score on the seven-point Patient Global Impression of Change scale at the end of the maintenance period. The analysis plan examined the differences of the 30-mg and 45-mg twice-daily AP groups from the placebo group. Comparison of the AP groups with the placebo group did not reach statistical significance on either of the co-primary endpoints for either of the AP doses.
The most commonly reported adverse event was somnolence (2%, 7%, 16%, and 21% for placebo and for AP 15 mg, 30 mg, and 45 mg twice daily, respectively). Seven subjects experienced treatment-emergent serious adverse events, none of which was judged to be related to the study drug.
Source: XenoPort; May 20, 2013.