GlaxoSmithKline and XenoPort, Inc announced top-line results from a phase-II clinical trial evaluating GSK1838262/XP13512 (gabapentin enacarbil) in adult patients with neuropathic pain associated with post-herpetic neuralgia (PHN) who have had a history of inadequate response to gabapentin doses of 1800 mg/day or higher. In this double-blind, two-period cross-over study, 3600 mg/day of GSK 1838262 demonstrated a statistically significant improvement over 1200 mg/day of GSK1838262 on the primary endpoint, which was the change from baseline to the end of the treatment period in the 24-hour average pain intensity score. A greater reduction in the 24-hour average pain score was observed for the 3600 mg/day than for the 1200 mg/day (adjusted difference of -0.29; p= 0.013.)
This study enrolled 138 subjects diagnosed with PHN who had been experiencing pain for at least three months following healing of the herpes zoster skin rash. Subjects with a history of inadequate response to gabapentin entered a baseline period where they received a dose of 1800 mg/day of gabapentin for two weeks. Subjects (N=96) who had a 24-hour average pain score of at least four on the 11 point pain intensity rating scale were then randomized to receive either 1200 mg/day of GSK1838262 for the first 28-day treatment period followed by 3600 mg/day for the second 28-day treatment period, or 3600 mg/day followed by 1200 mg/day. Subjects received 2400 mg/day of GSK1838262 for four days in between the two treatment periods.
The only treatment-emergent adverse event occurring in ≥5% of subjects taking GSK1838262 was nasopharyngitis (5%). Among the other adverse events noted in this study, dizziness and somnolence occurred at rates of 4% and 3%, respectively, and were mild in intensity. Withdrawals due to adverse events during GSK1838262 treatment occurred in 3% of subjects.
"These results from another positive study of GSK1838262 in the treatment of PHN will be important as we evaluate our next steps in the development program for neuropathic pain," said Atul Pande, senior vice president, GlaxoSmithKline Neurosciences Medicines Development Center.
"Clinical trial experience has shown that there are PHN patients who do not experience adequate pain relief," said Ronald W Barrett, chief executive officer of XenoPort. "We are encouraged by these Phase II results and plan to share further details about the study at a future medical meeting."
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.