title: The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia.
abstract: OBJECTIVE
  To assess the acute effects of SB-649868 in male subjects with Primary Insomnia with regard to (1) objective and subjective sleep parameters, (2) safety and tolerability, (3) next-day residual effects.
  
  
  METHODS
  Multicenter, randomized, double-blind, placebo-controlled crossover study using a complete set of Williams orthogonal Latin Squares
  
  
  METHODS
  9 sleep centers in Germany
  
  
  METHODS
  52 male subjects with a diagnosis of primary insomnia (difficulty in sleep initiation and maintenance) confirmed by polysomnography
  
  
  METHODS
  SB-649868 (10, 30, 60 mg) and placebo administered after dinner 90 minutes before bedtime
  
  
  RESULTS
  Sleep effects assessed by polysomnography during 2 consecutive nights and by sleep questionnaires completed by subjects after each night at the sleep laboratory. Safety and tolerability were assessed by adverse events collection, electrocardiogram (ECG), vital signs, laboratory tests. Next-day residual effects were assessed by Digit Symbol Substitution Test, and modified Verbal Learning Memory Test administered at "lights on" after night 2. SB-649868 significantly reduced latency to persistent sleep, wake after sleep onset (WASO), and increased total sleep time (TST) compared to placebo. A dose-dependent effect was observed. A dose-dependent increase in absolute and percent REM sleep and reduction in REM sleep latency was observed mainly at the 60-mg dose. SB-649868 was well tolerated with inconsistent next day residual effects. SB-649868 sleep effects were correlated with SB-649868 circulating levels.
  
  
  CONCLUSIONS
  The data demonstrate the sleep-promoting properties of the orexin antagonist SB-649868 in male patients with insomnia.
authors.affiliation: Neuroscience CEDD Discovery Medicine, GlaxoSmithKline, Verona, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bettica
authors.forename: Lisa
authors.initials: L
authors.lastname: Squassante
authors.forename: Stefano
authors.initials: S
authors.lastname: Zamuner
authors.forename: Gianluca
authors.initials: G
authors.lastname: Nucci
authors.forename: Heidi
authors.initials: H
authors.lastname: Danker-Hopfe
authors.forename: Emiliangelo
authors.initials: E
authors.lastname: Ratti
mesh_terms: D000293:Adolescent; D000328:Adult; D001572:Benzofurans / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005858:Germany; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D009479:Neuropeptides / Q000037:antagonists & inhibitors*; D000068797:Orexins; D010919:Placebos; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D011795:Surveys and Questionnaires; D013844:Thiazoles / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D013997:Time Factors; D055815:Young Adult
chemical_list: D001572:Benzofurans; D047908:Intracellular Signaling Peptides and Proteins; C557781:N-((1-((5-(4-fluorophenyl)-2-methyl-4-thiazolyl)carbonyl)-2-piperidinyl)methyl)-4-benzofurancarboxamide; D009479:Neuropeptides; D000068797:Orexins; D010919:Placebos; D013844:Thiazoles