title: Efficacy of gabapentin enacarbil in adult patients with severe primary restless legs syndrome.
abstract: Assess efficacy and tolerability of gabapentin enacarbil (GEn) in adults with severe primary restless legs syndrome (RLS).
  
  
  
  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.
  
  
  
  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%).
  
  
  
  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.
authors.affiliation: Baptist Health Neurology, 789 Eastern Bypass Suite 16, Richmond, KY 40475, USA. Electronic address: daniel.lee@bhsi.com.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Lee
authors.affiliation: Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Buchfuhrer
authors.affiliation: Sleep Research Institute, Alberto Alcocer 19, 28036 Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Garcia-Borreguero
authors.affiliation: UCLA Sleep Disorders Center, Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Boulevard, Los Angeles, CA 90095, USA.
authors.forename: Alon Y
authors.initials: AY
authors.lastname: Avidan
authors.affiliation: Cleveland Sleep Research Center, 17900 Jefferson Park Road, Suite 102, Middleburg Heights, OH 44130, USA.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8508, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Hays
authors.affiliation: University of Texas Health Science Center at Houston, 6410 Fannin Street, Suite 1010, Houston, TX 77030, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Ondo
authors.affiliation: Summit Analytical, LLC, 2422 Stout Street, Denver, CO 80205, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Jaros
authors.affiliation: XenoPort, Inc., 3410 Central Expressway, Santa Clara, CA 95051, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Kim
authors.affiliation: XenoPort, Inc., 3410 Central Expressway, Santa Clara, CA 95051, USA.
authors.forename: Gwendoline
authors.initials: G
authors.lastname: Shang
mesh_terms: D002219:Carbamates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: C493250:1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; D002219:Carbamates; D005680:gamma-Aminobutyric Acid
keywords: Clinical Global Impression − Improvement; Gabapentin enacarbil; International Restless Legs Scale; Mood; Restless legs syndrome; Sleep