title: Ramelteon 8 mg/d versus placebo in patients with chronic insomnia: post hoc analysis of a 5-week trial using 50% or greater reduction in latency to persistent sleep as a measure of treatment effect.
abstract: BACKGROUND
  Ramelteon is a selective MT1/MT2 melatonin receptor agonist approved by the US Food and Drug Administration for insomnia treatment.
  
  
  OBJECTIVE
  The aim of this post hoc analysis was to compare the efficacy and tolerability of ramelteon 8 mg/d versus placebo in adults with chronic insomnia.
  
  
  METHODS
  This study analyzed data from a previously published 5-week, randomized, double-blind, placebo-controlled study. Patients aged 18 to 64 years with chronic insomnia were randomly assigned to receive ramelteon 8 or 16 mg/d or placebo QD for 5 weeks. Sleep parameters were evaluated using polysomnography at weeks 1, 3, 5, and 6 (placebo runout). In this post hoc analysis, patients who received ramelteon 8 mg (approved dose) or placebo in the original study were evaluated using a primary end point of a=50% reduction from baseline in latency to persistent sleep (LPS).
  
  
  RESULTS
  A total of 270 adults (ramelteon 8 mg, 139 patients, mean age, 38.0 years; placebo, 131 patients, mean age, 39.7 years) met the criteria for inclusion in this analysis. One patient from the original study (ramelteon 8-mg/d group) was excluded from the post hoc analysis based on a lack of evaluable LPS data. Ramelteon was associated with significantly greater proportions of patients who achieved a > or = 50% reduction in LPS compared with placebo at weeks 1 (63.0% vs 39.7%; P < 0.001), 3 (63.0% vs 41.2%; P < 0.001), and 5 (65.9% vs 48.9%; P < 0.005). No rebound insomnia or withdrawal effects were observed. Headache (19.4% and 18.3%), fatigue (9.4% and 2.3%), and somnolence (7.9% and 1.5%) were the most common adverse events.
  
  
  CONCLUSIONS
  In this post hoc analysis of data from patients with chronic insomnia, a significantly greater percentage experienced a > or = 50% reduction in LPS with ramelteon 8 mg/d versus placebo. This improvement was evident at week 1 and was sustained through 5 weeks of treatment. Ramelteon 8 mg was well tolerated in this study, with no evidence of withdrawal or rebound insomnia.
authors.affiliation: Takeda Pharmaceuticals North America, Inc., Deerfield, Illinois 60015, USA. lmini@tpna.com
authors.forename: Louis
authors.initials: L
authors.lastname: Mini
authors.forename: Sherry
authors.initials: S
authors.lastname: Wang-Weigand
authors.forename: Jeff
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007192:Indenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D044122:Receptor, Melatonin, MT1 / Q000819:agonists*; D044123:Receptor, Melatonin, MT2 / Q000819:agonists*; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D013997:Time Factors
chemical_list: D007192:Indenes; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; C495910:ramelteon