GlaxoSmithKline and XenoPort, Inc announced top-line results from a phase-IIb clinical trial evaluating the safety and efficacy of GSK1838262/XP13512 (gabapentin enacarbil) for neuropathic pain associated with post-herpetic neuralgia (PHN) in adults. In this study, subjects were randomized to receive placebo, 1200, 2400 or 3600 mg/day of GSK1838262 dosed twice a day. All doses of GSK1838262 demonstrated statistically significant improvements over placebo on the primary endpoint, which was the change from baseline to the end of maintenance treatment in the 24-hour average pain intensity score.
This 14-week, double-blind, placebo-controlled study enrolled 376 subjects with PHN who had been experiencing pain for at least three months following healing of the herpes zoster skin rash. The pre-specified statistical analysis included adjustment for comparisons of multiple GSK1838262 doses to placebo. The adjusted p-values for comparison of 1200, 2400 and 3600 mg/day doses to placebo were 0.013, 0.029 and 0.002, respectively.
GSK1838262 was generally well tolerated at all doses in this study. The most common adverse events were dizziness (placebo 15%, 1200 mg/day 17%, 2400 mg/day 26% and 3600 mg/day 30%) and somnolence (8%, 10%, 11% and 14%, respectively). Most of these adverse events were mild or moderate in intensity. Withdrawals due to adverse events were 13%, 6%, 15% and 18%, respectively.
"We are encouraged by the positive results in this study of GSK1838262 in treating neuropathic pain associated with PHN, which is a debilitating condition for affected patients. We look forward to sharing the full results at a future medical meeting," said Atul Pande, senior vice president, GlaxoSmithKline Neurosciences Medicines Development Center. "We are currently evaluating the next steps for the development of this compound for the treatment of neuropathic pain."
Ronald W Barrett, chief executive officer of XenoPort said, "We are pleased with the efficacy and tolerability results observed across all doses in this study. These results build upon the positive Phase IIa study in PHN patients we previously conducted with this product candidate. We look forward to continuing to work with GSK to advance the development of this compound in neuropathic pain."
Post-herpetic neuralgia is a neuropathic pain syndrome that primarily affects people over fifty and often results in disability.
GSK1838262 is a new chemical entity that is designed to provide dose proportional and sustained exposure of gabapentin by taking advantage of high-capacity transport mechanisms in the gastrointestinal tract.