Gabapentin enacarbil in restless legs syndrome: a phase 2b, 2-week, randomized, double-blind, placebo-controlled trial

Clin Neuropharmacol. Nov-Dec 2009;32(6):311-20. doi: 10.1097/WNF.0b013e3181b3ab16.

Abstract

Objectives: Assess the efficacy and tolerability of gabapentin enacarbil (GEn), a transported prodrug of gabapentin with improved gabapentin exposure, in adults with moderate-to-severe primary restless legs syndrome.

Methods: This 14-day, double-blind, randomized, controlled trial of GEn at 1200 or 600 mg or placebo taken once daily, evaluated the mean change from baseline International Restless Legs Scale (IRLS) total score at end of treatment (day 14:primary comparison, GEn at 1200 mg vs placebo). Secondary end points included Clinical Global Impression-Improvement scale outcomes at day 14.

Results: Ninety-five subjects were randomized (GEn: 1200 mg, n = 33 and 600 mg, n = 29; placebo, n = 33); 2 subjects (GEn at 1200 mg) withdrew because of adverse events. At day 14,the mean (SD) change from baseline IRLS total score was significantly greater with GEn at 1200 mg (-16.1 [7.93]) compared with placebo (-8.9 [7.72]; adjusted mean treatment difference, -7.2; P < 0.0001). Investigator-rated Clinical Global Impression-Improvement scale responses also significantly favored GEn at 1200 mg compared with placebo (P G 0.0001).The mean (SD) change from baseline IRLS total score with GEn at 600 mg at day 14 was -9.1 (5.95), similar to placebo. The most commonly reported treatment-emergent adverse events were somnolence (GEn: 1200 mg, 36% and 600 mg, 14%; placebo,15%) and dizziness (GEn: 1200 mg, 18% and 600 mg, 14%; placebo, 3%), most of which were rated mild or moderate in intensity.

Conclusions: Gabapentin enacarbil at 1200 mg significantly improved restless legs syndrome symptoms compared with placebo. Efficacy outcomes for GEn at 600 mg were similar to placebo. Both GEn doses were generally well tolerated.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects
  • Affect / physiology
  • Aged
  • Carbamates / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain / drug therapy
  • Pain / physiopathology
  • Prodrugs / therapeutic use*
  • Restless Legs Syndrome / drug therapy*
  • Restless Legs Syndrome / physiopathology
  • Sleep / drug effects
  • Sleep / physiology
  • Treatment Outcome
  • Young Adult
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • 1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid
  • Carbamates
  • Prodrugs
  • gamma-Aminobutyric Acid