XenoPort announced preliminary top-line results from a phase IIb clinical trial of arbaclofen placarbil (also known as AP) as adjunctive therapy in patients with gastroesophageal reflux disease (GERD) who do not experience complete relief of GERD symptoms while being treated with proton pump inhibitors (PPI). In this study, subjects who experienced GERD symptoms despite PPI therapy were randomized to receive a PPI plus placebo, or a PPI plus one of four AP dose regimens (20mg or 40mg of AP dosed once daily (QD), or 20mg or 30mg of AP dosed twice daily (BID)), for six weeks. None of the AP doses showed statistically significant improvements over placebo in the analysis of the primary endpoint. Analyses of key secondary endpoints did not yield consistent results when AP doses were compared to placebo.
The randomized, double-blind, placebo-controlled phase IIb clinical trial was conducted at 58 sites in the U.S. and Canada. The primary efficacy endpoint was percent change from baseline in heartburn events per week with the primary analysis evaluating percent change from baseline in heartburn events at week six. Percent change in weekly heartburn events was analyzed using a repeated measures ANCOVA model. At week six, subjects in the placebo group showed a mean percent reduction in heartburn events of 68%. Although there were trends for improvement over placebo in the AP dose groups, none of the comparisons to placebo reached statistical significance.
AP was safe and generally well tolerated at all dose levels. The most common adverse events in the combined AP dose groups were somnolence, dizziness and nausea that occurred in 16%, 13% and 11% of subjects, respectively, compared to 2%, 3% and 6% of subjects in the placebo group. Most reported adverse events were mild or moderate in severity. Withdrawals due to adverse events were 6% in subjects receiving placebo and 16% in subjects receiving AP. The most common reasons for withdrawal were nausea, somnolence, dizziness and headache, none of which exceeded 5%.