title: Randomized, double-blind, placebo-controlled, phase II trial of gabapentin enacarbil for migraine prophylaxis.
abstract: OBJECTIVE
  The objective of this article is to evaluate the efficacy and safety of gabapentin enacarbil (GEn) for migraine prophylaxis.
  
  
  METHODS
  In this randomized, double-blind, parallel-group study, patients with International Headache Society-defined migraine who met criteria suggesting the need for prophylactic therapy were randomized 2:1:2:2:1 to one of the following five groups, designated according to target daily dose of study medication during the 20-week treatment period: placebo, GEn 1200 mg, GEn 1800 mg, GEn 2400 mg, or GEn 3000 mg.
  
  
  RESULTS
  The intent-to-treat population included 523 patients (n = 128 placebo, n = 66 GEn 1200 mg, n = 134 GEn 1800 mg, n = 133 GEn 2400 mg, n = 62 GEn 3000 mg). No statistically significant difference between active treatment (the average of 1800 mg and 2400 mg treatment groups) and placebo was found for change from baseline in the number of migraine headache days during the last four weeks of treatment prior to taper (the primary endpoint). Results of analyses of the primary endpoint using the per protocol population, analyses using imputation methods different from those of the primary analysis, and nonparametric analyses were consistent with the primary analysis in showing no difference between active treatment and placebo. The pattern of results was similar for the secondary efficacy endpoints. Pharmacokinetic data demonstrate that patients had adequate estimated exposure to GEn. The adverse event profile of GEn was consistent with that in previous studies.
  
  
  CONCLUSIONS
  GEn did not significantly differ from placebo for migraine headache prophylaxis. A high placebo effect should be considered when interpreting these results.
authors.affiliation: Jefferson Headache Center, Philadelphia, PA 19107, USA. stephen.silberstein@jefferson.edu
authors.forename: Stephen
authors.initials: S
authors.lastname: Silberstein
authors.forename: Stacey
authors.initials: S
authors.lastname: Goode-Sellers
authors.forename: Colleen
authors.initials: C
authors.lastname: Twomey
authors.forename: Jane
authors.initials: J
authors.lastname: Saiers
authors.forename: John
authors.initials: J
authors.lastname: Ascher
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000175:diagnosis* / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects*; D015990:Placebo Effect; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: C493250:1-(((alpha-isobutanoyloxyethoxy)carbonyl)aminomethyl)-1-cyclohexaneacetic acid; D000927:Anticonvulsants; D002219:Carbamates; D005680:gamma-Aminobutyric Acid