Efficacy of gabapentin enacarbil in adult patients with severe primary restless legs syndrome

Sleep Med. 2016 Mar;19:50-6. doi: 10.1016/j.sleep.2015.11.002. Epub 2015 Nov 14.


Aim: Assess efficacy and tolerability of gabapentin enacarbil (GEn) in adults with severe primary restless legs syndrome (RLS).

Methods: We pooled data from three 12-week, double-blind, placebo-controlled, randomized trials (NCT00298623, NCT00365352, NCT01332305) across GEn 600-mg, GEn 1200-mg, and placebo treatment groups for severe primary RLS (baseline International Restless Legs Scale (IRLS) total score ≥24). Co-primary end points at week 12 were mean change from baseline in IRLS total score and proportion of responders ("much"/very much" improved) on the investigator-rated Clinical Global Impression - Improvement (CGI-I) Scale. Outcomes for individual IRLS items (eg, sleep, mood, quality of life, pain, safety) were assessed.

Results: A total of 309 patients had severe primary RLS (placebo, n = 110; GEn 600 mg, n = 80; GEn 1200 mg, n = 119). GEn 600 mg and 1200 mg significantly improved least-squares mean IRLS total scores versus placebo at week 12 (placebo, -12.3; GEn 600 mg, -16.3; GEn 1200 mg, -18.0; treatment difference vs. placebo, both p <0.01). Significantly more patients with severe primary RLS treated with GEn 600 mg (64%) and 1200 mg (74%) were CGI-I responders at week 12 versus placebo (42%; p <0.01 for both GEn doses). Both GEn doses led to significant improvements in the other outcomes explored versus placebo at week 12. The most frequent treatment-emergent adverse events (TEAEs) were somnolence (GEn, 21-24%; placebo, 3%) and dizziness (GEn, 14-19%; placebo, 3%).

Conclusions: GEn (600 mg or 1200 mg) once daily significantly improved RLS symptoms and consequences of these symptoms in severe primary RLS. The most frequent TEAEs were somnolence and dizziness.

Keywords: Clinical Global Impression − Improvement; Gabapentin enacarbil; International Restless Legs Scale; Mood; Restless legs syndrome; Sleep.

MeSH terms

  • Carbamates / administration & dosage*
  • Dose-Response Relationship, Drug*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Quality of Life
  • Randomized Controlled Trials as Topic*
  • Restless Legs Syndrome / drug therapy*
  • gamma-Aminobutyric Acid / administration & dosage
  • gamma-Aminobutyric Acid / analogs & derivatives*


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