XenoPort, Inc. (Nasdaq:XNPT) announced today preliminary top-line results from a Phase 2b 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 (20 mg or 40 mg of AP dosed once daily (QD), or 20 mg or 30 mg 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.
Ronald W. Barrett, Ph.D., XenoPort's chief executive officer, stated, "We are disappointed that AP failed to demonstrate clear efficacy over placebo in this trial. While we will continue to analyze the data, at this time, we do not believe the efficacy results of this study warrant our investment in further development for AP in GERD. We believe the AP safety profile observed in this study continues to support our planned Phase 3 development program for AP in patients with spasticity."
The randomized, double-blind, placebo-controlled Phase 2b clinical trial was conducted at 58 sites in the United States and Canada. The trial included a run-in period of up to four weeks whereby GERD patients with a history of incomplete response to a PPI were monitored while on PPI therapy. Subjects>
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. There were six treatment emergent serious adverse events in five subjects, including one death that was due to arteriosclerosis, but none were assessed as related to AP. 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%.
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