University of Oulu

Jane Yardley, Mikko Kärppä, Yuichi Inoue, Kate Pinner, Carlos Perdomo, Kohei Ishikawa, Gleb Filippov, Naoki Kubota, Margaret Moline, Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial, Sleep Medicine, Volume 80, 2021, Pages 333-342, ISSN 1389-9457,

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder : results from a phase 3 randomized clinical trial

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Author: Yardley, Jane1; Kärppä, Mikko2; Inoue, Yuichi3;
Organizations: 1Eisai Ltd., Hatfield, UK
2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
3Tokyo Medical University, Tokyo, Japan
4Eisai Inc., 100 Tice Boulevard, Woodcliff Lake, NJ 07677, USA
5Eisai Co., Ltd, Tokyo, Japan
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: Elsevier, 2021
Publish Date: 2021-07-08


Objective/background: Lemborexant is a dual orexin receptor antagonist approved in the United States, Japan, and Canada for the treatment of insomnia in adults. We report effectiveness and safety outcomes in subjects with insomnia who received up to twelve months of continuous lemborexant treatment in Study E2006-G000-303 (Study 303; SUNRISE-2).

Patients/methods: Study 303 was a twelve-month, global, multicenter, randomized, double-blind, parallel-group, Phase 3 study divided into two treatment periods. In Treatment Period 1 (first six months), subjects (n = 949, Full Analysis Set) were randomized to daily placebo, lemborexant 5 mg (LEM5) or lemborexant 10 mg (LEM10). In Treatment Period 2 (second six months), placebo subjects were rerandomized to LEM5 or LEM10, and subjects randomized to lemborexant continued their assigned treatment (LEM5, n = 251; LEM10, n = 226). Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored.

Results: For all sleep parameters, the significant benefits observed with LEM5 and LEM10 versus placebo over six months were maintained at twelve months in subjects who received twelve continuous months of treatment. There was no evidence of rebound insomnia or withdrawal in either lemborexant group following treatment discontinuation. Over twelve months of lemborexant treatment, most TEAEs were mild/moderate; the most common TEAEs were nasopharyngitis, somnolence and headache.

Conclusions: LEM5 and LEM10 had significant benefit on sleep onset and sleep maintenance compared with placebo, and importantly, lemborexant effectiveness persisted at twelve months, suggesting that lemborexant may provide long-term benefits for subjects with insomnia.

Clinical trial registration:, NCT02952820;, EudraCT Number 2015-001463-39.

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Series: Sleep medicine
ISSN: 1389-9457
ISSN-E: 1878-5506
ISSN-L: 1389-9457
Volume: 80
Pages: 333 - 342
DOI: 10.1016/j.sleep.2021.01.048
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
Funding: This study was sponsored by Eisai Inc. (Woodcliff Lake, NJ, USA), the owner and manufacturer of lemborexant. The study sponsor participated in the study design, data collection/analysis, data interpretation and development and approval of the submitted manuscript.
Copyright information: © 2021 Eisai Inc. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (