XenoPort, Inc. (Nasdaq:XNPT) announced today positive preliminary results from a Phase 2 clinical trial of arbaclofen placarbil (AP), also known as XP19986, for the treatment of patients with spasticity due to spinal cord injury (SCI). Doses of 20 and 30 mg of AP, given twice daily (BID), demonstrated statistically significant improvements compared to placebo for the primary endpoint of the study. AP was well tolerated during the trial.

“Currently available medications for treating spasticity are often limited by their short duration of action and significant central nervous system side effects,” said David A. Stamler, M.D., XenoPort’s chief medical officer. “The efficacy and tolerability of AP that were observed in this trial was encouraging, and we believe that AP offers the potential to address important medical needs for SCI patients.”

This Phase 2 clinical trial was a randomized, double-blind, placebo-controlled, crossover study that enrolled 37 subjects at ten sites in the United States and Canada. Subjects with SCI between C-5 and T-12 discontinued spasticity therapy during a one-week washout period prior to a one-week placebo run-in period, at the end of which baseline assessments were conducted. Subjects had an Ashworth Scale score of at least 2 in one of six assessed muscle groups (hip abductors/adductors, knee flexors/extensors and ankle flexors/extensors) on the most affected leg. Subjects received either AP (10, 20 or 30 mg BID) or placebo in the first treatment segment of the two-segment crossover design. Each treatment segment included a titration period, followed by at least one week at the target dose, at which time efficacy assessments were performed (day 17 of each treatment segment). Each treatment segment also included a down-titration period, and there was a three-day washout between treatment segments.

The primary endpoint in this study was the difference in Ashworth Scale score during the placebo and AP treatment segments for the muscle group with the highest Ashworth Scale score at baseline. Ashworth Scale scores were determined by the investigator prior to dosing, and again two, four and six hours after the morning dose. The primary analysis used a repeated-measures analysis of variance model and included data from the 35 subjects who completed both treatment segments.

Mean maximum baseline Ashworth Scale scores were 3.2 (n=10), 3.1 (n=12) and 3.1 (n=13) for the 10, 20 and 30 mg BID AP dose cohorts, respectively. For the primary endpoint, the overall adjusted mean differences between placebo and AP over the six-hour assessment period for these cohorts were -0.17 (not significant), -0.60 (p=0.0059) and -0.88 (p=0.0007), respectively. AP treatment was associated with statistically significant differences from placebo at all time points in the 20 and 30 mg BID AP dose cohorts, indicating a treatment effect over the 12-hour dosing interval.