Issue Navigator

Volume 13 No. 11
Earn CME
Accepted Papers

Scientific Investigations

Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study

Patricia Murphy, PhD1; Margaret Moline, PhD1; David Mayleben, PhD2; Russell Rosenberg, PhD3; Gary Zammit, PhD4; Kate Pinner, MSc5; Shobha Dhadda, PhD1; Quan Hong, PhD1; Luigi Giorgi, MD5; Andrew Satlin, MD1
1Eisai Inc, Woodcliff Lake, New Jersey; 2Community Research Inc, Cincinnati, Ohio; 3NeuroTrials Research Inc, Atlanta, Georgia; 4CLINILABS, Inc, New York, New York; 5Eisai Ltd, Hatfield, United Kingdom

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.


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).


A total of 616 subjects were screened; 291 were randomized. Baseline characteristics were similar between lemborexant groups and placebo (∼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.


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:; Identifier: NCT01995838


Murphy P, Moline M, Mayleben D, Rosenberg R, Zammit G, Pinner K, Dhadda S, Hong Q, Giorgi L, Satlin A. Lemborexant, a dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. J Clin Sleep Med. 2017;13(11):1289–1299.

Please login to continue reading the full article

Subscribers to JCSM get full access to current and past issues of the JCSM.

Login to JCSM

Not a subscriber?

Join the American Academy of Sleep Medicine and receive a subscription to JCSM with your membership

Subscribe to JCSM:  $75/volume year for individuals or $140/volume year for institutions to access all current articles and archives published in JCSM.

Download this article*:   $20 to access a PDF version of a specific article from the current issue of JCSM.

*Purchase of an electronic download of JCSM provides permission to access and print the issue/article for personal scholarly, research and educational use. Please note: access to the article is from the computer on which the article is purchased ONLY. Purchase of the article does not permit distribution, electronic or otherwise, of the article without the written permission of the AASM. Further, purchase does not permit the posting of article text on an online forum or website.