Improvement in fatigue and sleep measures with the dual orexin receptor antagonist lemborexant in adults with insomnia disorder

ABSTRACT

Objective

Fatigue is a common symptom in patients with insomnia. This analysis evaluated whether treatment of nighttime symptoms of insomnia with a dual orexin receptor antagonist, lemborexant, might also reduce fatigue.

Methods

Analyses were conducted of two phase 3 studies of subjects with insomnia disorder. Subjects received placebo, lemborexant 5 mg, or lemborexant 10 mg in the 12-month (6 months placebo-controlled) Study E2006-G000-303 (Study 303: SUNRISE-2) of adults (N = 949; full analysis set [FAS]), and the 1-month, placebo- and active-controlled Study E2006-G000-304 (Study 304; SUNRISE-1) of older adults (females ≥55 years, males ≥65 years) (N = 1006; FAS). Fatigue was assessed using the Fatigue Severity Scale (FSS). Patient-reported sleep onset and maintenance endpoints were analyzed using data from electronic sleep diaries.

Results

Lemborexant significantly reduced subject-reported fatigue versus placebo over a 6-month treatment period (FSS total score least-squares mean treatment difference of −2.50 for 5 mg and −2.56 for 10 mg of lemborexant; p < 0.05 for both). This reduction was sustained over 12 months of lemborexant in both the overall population and in subjects with clinically meaningful fatigue (FSS total score ≥36) at baseline. Improvements in fatigue over time positively correlated with improvements in sleep onset and maintenance parameters. Improvements in sleep quality were evident as early as 1 week after lemborexant treatment, whereas longer-term treatment (>1 month) may be needed for improvements in insomnia-related fatigue.

Conclusions

In addition to improving sleep onset and sleep maintenance in subjects with insomnia disorder, lemborexant provides further benefit by reducing daytime fatigue.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT02952820 and https://clinicaltrials.gov/ct2/show/NCT02783729

Abbreviations

DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; FSS = Fatigue Severity Scale; ICSD-3 = International Classification of Sleep Disorders, Third Edition; LSM = least squares mean; sSE = subjective sleep efficiency; sSOL = subjective sleep onset latency; sTST = subjective total sleep time; sWASO = subjective sleep after wake onset.

KEYWORDS:

• Fatigue
• insomnia
• lemborexant
• orexin receptor antagonists
• sleep

This article is related to:

The Effects of Lemborexant on Insomnia-Related Fatigue: A Plain Language Summary

Acknowledgments

Eisai Inc. was involved in the design of the studies, data collection, data analysis, and preparation of the manuscript. Medical writing assistance was provided by Linda Donnini, PhD, CMPP, of Envision Pharma Group, and was funded by Eisai Inc. Envision’s services complied with international guidelines for Good Publication Practice (GPP3).

Social media

Craig Chepke: www.linkedin.com/in/craigchepke

Disclosure of financial/other conflicts of interest

Craig Chepke has received research support from Axsome Therapeutics and Harmony Biosciences; has served as a consultant to Corium; has served on the advisory board of Karuna; has received speakers fees from Merck and Sunovion; has received speaker fees and served on the advisory board for Intracellular, Ironshore, and Takeda; has received speaker fees, served as a consultant, and served on the advisory board for AbbVie, Alkermes, Eisai, Jazz, Lundbeck, Janssen, Noven, and Otsuka; has received speaker fees, served as a consultant, served on the advisory board for and has received research support from Acadia, Neurocrine, and Teva.

Margaret Moline is an employee of Eisai Inc.

Rakesh Jain has served as a consultant for Acadia, Alfasigma, Eisai, Evidera, Impel NeuroPharma, and Osmotica Pharmaceuticals; has received speaker fees from Ironshore Pharmaceuticals and Tris Pharmaceuticals; has received speaker fees and served on the advisory board for Alkermes; has served as a consultant for, received research support, and received speaker fees from Allergan; has served as a consultant and on the advisory board for Neurocrine Biosciences, Supernus, and Teva Pharmaceutical; has received speaker fees and has served as a consultant and on the advisory board for Janssen, Merck, Neos Therapeutics, Pamlab, and Sunovion Pharmaceuticals; and has received research support, speaker fees, and has served as a consultant and on the advisory board for Eli Lilly and Company, Lundbeck, Otsuka, Pfizer, Shire, and Takeda.

Russel Rosenberg has received grants from and is on the advisory board for Eisai.

Jane Yardley is an employee of Eisai, Ltd.

Kate Pinner is an employee of Eisai, Ltd.

Dinesh Kumar is an employee of Eisai Inc.

Carlos Perdomo is an employee of Eisai Inc.

Gleb Filippov was an employee of Eisai Inc. during the data analysis for this manuscript.

Norman Atkins was an employee of Eisai Inc. during the data analysis for this manuscript.

Manoj Malhotra is an employee of Eisai Inc.

A reviewer on this manuscript has disclosed that they are on the speakers’ bureau for Merck (suvorexant), Eisai (lemborexant), and Jazz (solreamfetol) pharma companies. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Geological information

Study 303 (SUNRISE-2) was conducted at a total of 119 sites in North America, Europe, Asia, and Oceania. Study 304 (SUNRISE-1) was conducted at 67 sites in North America and Europe.

Data availability statement

De‐identified subject data that underlie the results reported in this article will not be made available, but summary information will be available on ClinicalTrials.gov.

Clinical trial registration

SUNRISE-2 (ClinicalTrials.gov identifier: NCT02952820) and SUNRISE-1 (ClinicalTrials.gov identifier: NCT02783729).

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

The studies were supported by Eisai Inc., the owner and manufacturer of lemborexant.