title: Randomized controlled trial of the orexin receptor antagonist filorexant for migraine prophylaxis.
abstract: BACKGROUND
  This study explored whether antagonism of orexin receptors might be an effective mechanism for migraine prevention.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled, pilot trial. Patients experiencing four to 14 days with migraine during a one-month baseline period were randomized to the orexin receptor antagonist filorexant 10 mg nightly or placebo for three months. Efficacy was assessed by mean monthly migraine days (headache plus at least one associated migraine symptom) and headache days. Safety and tolerability were assessed by adverse event reports and laboratory tests.
  
  
  RESULTS
  Of 120 patients treated with filorexant and 115 treated with placebo, 97 (81%) and 101 (88%), respectively, completed the trial. There was no statistically significant difference between treatments for change from baseline in mean monthly migraine days (filorexant = -1.7, placebo = -1.3, difference = -0.4 (95% CI: -1.3, 0.4)) or headache days (filorexant = -1.7, placebo = -1.2, difference = -0.5 (95% CI: -1.4, 0.4)). Filorexant was generally well tolerated but was associated with a higher proportion of patients who reported adverse events than placebo (47% vs 37%), particularly somnolence (13% vs 4%).
  
  
  CONCLUSIONS
  These data fail to provide evidence that antagonism of orexin receptors with filorexant, when administered at night, is effective for migraine prophylaxis.
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: Almira
authors.initials: A
authors.lastname: Chabi
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: Saheeda
authors.initials: S
authors.lastname: Jackson
authors.affiliation: Headache Care Center, Springfield, MO, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Cady
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: Herring
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Connor
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA david.michelson@merck.com.
authors.forename: David
authors.initials: D
authors.lastname: Michelson
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000517:prevention & control*; D000068796:Orexin Receptor Antagonists / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: C573816:MK-6096; D000068796:Orexin Receptor Antagonists; D010880:Piperidines; D011743:Pyrimidines
keywords: Filorexant; MK-6096; migraine; orexin; prophylaxis