Peripheral Edema and Weight Gain in Adult Patients with Painful Diabetic Peripheral Neuropathy (DPN) Receiving Gabapentin Enacarbil (GEn) or Pregabalin Enrolled in a Randomized Phase 2 Trial (I6-1.004)

OBJECTIVE: To examine the incidences of peripheral edema and weight gain in adult patients with painful DPN receiving GEn, pregabalin, or placebo in a phase 2 trial. BACKGROUND: GEn is an actively transported prodrug of gabapentin. In this 20-week, randomized phase 2 study in patients with neuropathic pain attributed to DPN, neither the GEn (1200 mg/day, 2400 mg/day, or 3600 mg/day) nor control (pregabalin 300 mg/day) arms differed from placebo with regard to the primary efficacy endpoint (change from baseline in the mean 24-hour average pain intensity score). GEn was well tolerated across dosages. DESIGN/METHODS: The adverse events peripheral edema and weight gain were further explored in this analysis. RESULTS: The safety population comprised 420 patients. Compared with pregabalin, patients randomized to GEn experienced less peripheral edema and weight gain. The incidences for peripheral edema were: GEn, 3% (1200 mg), 0% (2400 mg), and 9% (3600 mg); pregabalin, 17%; placebo, 4%. The incidences for weight gain were: GEn, 0% (1200 mg), 4% (2400 mg), and 4% (3600 mg); pregabalin, 8%; placebo, 1%. The proportions of patients who experienced a 蠅7% weight gain at any post-randomization visit were: GEn, 5% (1200 mg), 7% (2400 mg), and 10% (3600 mg); pregabalin, 15%; placebo, 3%. The mean (2SE) changes from baseline in weight gain at the end of the 12-week maintenance treatment phase were 1.22 (0.95), 1.71 (0.84), and 1.85 (0.77) kg for GEn 1200, 2400, and 3600 mg, respectively, 2.65 (0.92) kg for pregabalin, and −0.55 (0.72) kg for placebo. CONCLUSIONS: In this phase 2 study in patients with painful DPN, GEn was associated with overall lower incidences of peripheral edema and weight gain than pregabalin; the weight gain in GEn-treated patients appeared to be dose-dependent. Data support examination in future clinical trials. Study Supported by: Xenoport, Inc. Disclosure: Dr. Calkins has received personal compensation for activities with Purdue University, Salix, Teva Neuroscience, Pfizer Inc., and Depomed. Dr. Shurman has received personal compensation for activities with Millennium, Xenoport Inc., Insys, Purdie Frederick, Teva Neuroscience, Empi-Donjoy, Takeda, RS Medical, Covidien, and Mallinckr. Dr. Jaros has received personal compensation for activities with XenoPort, Inc. as an employee. Dr. Kim has received personal compensation for activities with XenoPort, Inc. as an employee. Dr. Shang has received personal compensation for activities with XenoPort, Inc. as an employee.