title: A single-dose, randomized, double-blind, double dummy, placebo and positive-controlled, five-way cross-over study to assess the pharmacodynamic effects of lorediplon in a phase advance model of insomnia in healthy Caucasian adult male subjects.
abstract: OBJECTIVE
  A 5-h phase advance model of insomnia was used to evaluate the efficacy of lorediplon, a new non-benzodiazepine hypnotic.
  
  
  METHODS
  Thirty-five male, healthy subjects were included in a five-way randomized cross-over study. During each of the periods, sleep was recorded, and residual effects were measured. All subjects received lorediplon 1, 5, and 10 mg, placebo, and zolpidem 10 mg (i.e., active control).
  
  
  RESULTS
  Polysomnographic evaluation revealed that lorediplon (5 and 10 mg) significantly decreased wake after sleep onset (WASO) and increased total sleep time. Analysis by quarters of the night showed a progressive increasing effectiveness of lorediplon 10 mg across the first three quarters. Lorediplon increased non-rapid eye movement slow wave sleep and stage N2 sleep in the second and third quarters. The magnitude of these effects was dose related, with minimal effects seen with 1 mg. No residual effects were observed 13 h post dose.
  
  
  CONCLUSIONS
  Lorediplon demonstrated a dose-dependent improvement in sleep, whereas zolpidem showed a more sustained WASO effect. No next-day hangover effects were observed. These sleep effects are also consistent with the pharmacokinetic profile of lorediplon. These results warrant clinical trials in patients with insomnia.
authors.affiliation: R&D Centre, Ferrer Internacional S.A., Barcelona, Spain.
authors.forename: Lucy
authors.initials: L
authors.lastname: Horoszok
authors.forename: Thais
authors.initials: T
authors.lastname: Baleeiro
authors.forename: Fabiana
authors.initials: F
authors.lastname: D'Aniello
authors.forename: Savion
authors.initials: S
authors.lastname: Gropper
authors.forename: Benjamin
authors.initials: B
authors.lastname: Santos
authors.forename: Antonio
authors.initials: A
authors.lastname: Guglietta
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D017286:Polysomnography; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology; D012894:Sleep Stages / Q000187:drug effects; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D044465:White People; D055815:Young Adult; D000077334:Zolpidem
chemical_list: D006993:Hypnotics and Sedatives; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D000077334:Zolpidem; C000593976:lorediplon
keywords: clinical trial; insomnia; lorediplon; phase advanced model; sleep maintenance; zolpidem