GlaxoSmithKline and XenoPort, Inc announced results from a phase-II clinical trial of GSK1838262/XP13512 (gabapentin enacarbil) for neuropathic pain associated with diabetic peripheral neuropathy (DPN) in adults. GSK1838262 did not demonstrate a statistically significant improvement on the primary endpoint when compared to placebo, based on the change from baseline to end of treatment on the Pain Intensity-Numerical Rating Scale (PI-NRS). The pregabalin active control arm also did not differentiate from placebo on this same endpoint. The failure of the study to demonstrate a statistically significant benefit on the primary endpoint may be a consequence of the unexpectedly high placebo response rate observed in the study.

This 14-week, double-blind, placebo-controlled study enrolled 421 patients who were diagnosed with either Type 1 or Type 2 diabetes mellitus with signs and symptoms of DPN. Patients were randomized to receive either 1200 mg/day, 2400 mg/day or 3600 mg/day of GSK1838262 administered in divided doses twice daily, 300 mg/day of pregabalin as an active control, administered in divided doses three times daily, or placebo.

Throughout the study, GSK1838262 was generally well tolerated; the two most frequently reported adverse events were dizziness and somnolence.

"Although we are disappointed that neither GSK1838262 nor pregabalin demonstrated a clear clinical benefit over placebo in this study, we will be evaluating the study results further in order to determine our next steps," said Atul Pande, senior vice president, GlaxoSmithKline Neurosciences Medicines Development Center.

Ronald W Barrett, chief executive officer of XenoPort, stated, "A high placebo response is not uncommon in DPN studies, and this has been a contributing factor to several failed studies testing different drugs in this patient population. The failure of pregabalin in this study makes it difficult to draw definitive conclusions about the efficacy of GSK1838262. We are encouraged by the observation that all doses of GSK1838262 were generally well tolerated, particularly since the 3600 mg dose represents the highest dose tested in a study of this length."

GSK1838262 is a new chemical entity that is designed to improve upon the pharmacokinetics of gabapentin by taking advantage of high-capacity transport mechanisms in the gastrointestinal tract to improve absorption.

XenoPort is a biopharmaceutical company focused on developing a portfolio of internally discovered product candidates that utilize the body's natural nutrient transport mechanisms to improve the therapeutic benefits of existing drugs.