A Randomized, Double-Blind, Placebo-Controlled, Dose-Response Study to Assess the Pharmacokinetics, Efficacy, and Safety of Gabapentin Enacarbil in Subjects With Restless Legs Syndrome

Clinical Neuropharmacology, 07/27/2012

Gabapentin exposure was approximately proportional to gabapentin enacarbil (GEn) dose. Efficacy data showed that a once–daily dose of GEn 600 to 2400 mg provides greater relief of restless legs syndrome (RLS) symptoms than placebo; GEn was generally well tolerated with an adverse event profile consistent with gabapentin.

Methods

  • Subjects with RLS (n=217) were randomized to receive once-daily, orally administered GEn 600 (n=48), 1200 (n=45), 1800 (n=38), or 2400 mg (n=45) or placebo (n=41) in this 12-week, double-blind, multicenter study (NCT01332305).
  • Clinic visits were at screening, baseline, and weeks 1, 2, 3, 4, 6, 8, 10, and 12; plasma gabapentin concentrations were measured by a validated liquid chromatography-mass spectrometry/mass spectrometry method at weeks 4 and 12.

Results

  • Exposure to gabapentin was proportional to GEn dose.
  • Time to maximum plasma concentration was 7 to 9 hours, and elimination half-life was 6 hours.
  • The mean reduction from baseline to week 12 in International Restless Legs Syndrome Rating Scale total score and proportions of subjects with “much improved”/“very much improved” Clinical Global Impression-Improvement scores (investigator and patient ratings) ranged from -12.9 to -13.9 for GEn treatment groups versus -9.3 for placebo.
  • The 2 most commonly reported adverse events were somnolence and dizziness.

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