PMID- 29065953
OWN - NLM
STAT- MEDLINE
DCOM- 20180716
LR  - 20181113
IS  - 1550-9397 (Electronic)
IS  - 1550-9389 (Print)
IS  - 1550-9389 (Linking)
VI  - 13
IP  - 11
DP  - 2017 Nov 15
TI  - Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of 
      Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, 
      Placebo-Controlled Study.
PG  - 1289-1299
LID - 10.5664/jcsm.6800 [doi]
AB  - STUDY OBJECTIVES: To identify dose(s) of lemborexant that maximize insomnia 
      treatment efficacy while minimizing next-morning residual sleepiness and evaluate 
      lemborexant effects on polysomnography (PSG) measures (sleep efficiency [SE], 
      latency to persistent sleep [LPS], and wake after sleep onset [WASO]) at the 
      beginning and end of treatment. METHODS: Adults and elderly subjects with 
      insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders, 
      Fifth Edition were enrolled in a multicenter, randomized, double-blind, 
      placebo-controlled, Bayesian, adaptive, parallel-group study, receiving 
      lemborexant (1, 2.5, 5, 10, 15, 25 mg) or placebo for 15 nights. Efficacy 
      assessments included a utility function that combined efficacy (SE) and safety 
      (residual morning sleepiness as measured by Karolinska Sleepiness Scale [KSS]), 
      PSG measures, and sleep diary. Safety assessments included KSS, Digit Symbol 
      Substitution Test, computerized reaction time tests, and adverse events (AEs). 
      RESULTS: A total of 616 subjects were screened; 291 were randomized. Baseline 
      characteristics were similar between lemborexant groups and placebo ( approximately 63% female, 
      median age: 49.0 years). The study was stopped for early success after the fifth 
      interim analysis when the 15-mg dose met utility index/KSS criteria for success; 
      3 other doses also met the criteria. Compared with placebo, subjects showed 
      significant improvements in SE, subjective SE, LPS, and subjective sleep onset 
      latency at the beginning and end of treatment for lemborexant doses >/= 5 mg (P < 
      .05). WASO and subjective WASO showed numerically greater improvements for doses 
      > 1 mg. AEs, mostly mild to moderate, included dose-related somnolence. 
      CONCLUSIONS: Lemborexant doses ranging from 2.5-10 mg provided efficacy for the 
      treatment of insomnia while minimizing next-morning residual sleepiness. CLINICAL 
      TRIAL REGISTRATION: Title: A Multicenter, Randomized, Double-blind, 
      Placebo-controlled, Parallel-group, Bayesian Adaptive Randomization Design, Dose 
      Response Study of the Efficacy of E2006 in Adults and Elderly Subjects With 
      Chronic Insomnia; URL: https://clinicaltrials.gov/ct2/show/NCT01995838; 
      Identifier: NCT01995838.
CI  - (c) 2017 American Academy of Sleep Medicine
FAU - Murphy, Patricia
AU  - Murphy P
AD  - Eisai Inc, Woodcliff Lake, New Jersey.
FAU - Moline, Margaret
AU  - Moline M
AD  - Eisai Inc, Woodcliff Lake, New Jersey.
FAU - Mayleben, David
AU  - Mayleben D
AD  - Community Research Inc, Cincinnati, Ohio.
FAU - Rosenberg, Russell
AU  - Rosenberg R
AD  - NeuroTrials Research Inc, Atlanta, Georgia.
FAU - Zammit, Gary
AU  - Zammit G
AD  - CLINILABS, Inc, New York, New York.
FAU - Pinner, Kate
AU  - Pinner K
AD  - Eisai Ltd, Hatfield, United Kingdom.
FAU - Dhadda, Shobha
AU  - Dhadda S
AD  - Eisai Inc, Woodcliff Lake, New Jersey.
FAU - Hong, Quan
AU  - Hong Q
AD  - Eisai Inc, Woodcliff Lake, New Jersey.
FAU - Giorgi, Luigi
AU  - Giorgi L
AD  - Eisai Ltd, Hatfield, United Kingdom.
FAU - Satlin, Andrew
AU  - Satlin A
AD  - Eisai Inc, Woodcliff Lake, New Jersey.
LA  - eng
SI  - ClinicalTrials.gov/NCT01995838
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20171115
PL  - United States
TA  - J Clin Sleep Med
JT  - Journal of clinical sleep medicine : JCSM : official publication of the American 
      Academy of Sleep Medicine
JID - 101231977
RN  - 0 (Drugs, Investigational)
RN  - 0 (Orexin Receptor Antagonists)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Bayes Theorem
MH  - Double-Blind Method
MH  - Drugs, Investigational/*therapeutic use
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Orexin Receptor Antagonists/*therapeutic use
MH  - Sleep Initiation and Maintenance Disorders/*drug therapy
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC5656478
OTO - NOTNLM
OT  - Bayesian method
OT  - insomnia
OT  - orexin receptor antagonists
EDAT- 2017/10/27 06:00
MHDA- 2018/07/17 06:00
PMCR- 2018/05/15
CRDT- 2017/10/26 06:00
PHST- 2017/02/06 00:00 [received]
PHST- 2017/08/25 00:00 [accepted]
PHST- 2018/05/15 00:00 [pmc-release]
PHST- 2017/10/27 06:00 [pubmed]
PHST- 2018/07/17 06:00 [medline]
PHST- 2017/10/26 06:00 [entrez]
AID - jc-17-00052 [pii]
AID - 10.5664/jcsm.6800 [doi]
PST - epublish
SO  - J Clin Sleep Med. 2017 Nov 15;13(11):1289-1299. doi: 10.5664/jcsm.6800.