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Randomized Controlled Trial
. 2024 Jan 1;20(1):57-65.
doi: 10.5664/jcsm.10788.

A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea

Jocelyn Y Cheng  1 , Daniel Lorch  2 , Alan D Lowe  3 , Naohisa Uchimura  4 , Nancy Hall  1 , Dhara Shah  1 , Margaret Moline  1
Affiliations
Randomized Controlled Trial

A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea

Jocelyn Y Cheng et al. J Clin Sleep Med. .

Abstract

Study objectives: To evaluate the respiratory safety of lemborexant among adults and older adults with moderate to severe obstructive sleep apnea (OSA).

Methods: E2006-A001-113 (Study 113; NCT04647383) was a double-blind, two-period crossover, placebo-controlled study in adults (ages ≥ 45 to ≤ 90 years, n = 33) with moderate (apnea-hypopnea index [AHI] score ≥ 15 to < 30 events/h, n = 13) or severe (AHI ≥ 30 events/h, n = 20) OSA. Participants were randomized to lemborexant 10 mg (LEM10) or placebo (PBO) for two treatment periods of 8 nights with a ≥ 14-day washout period. AHI and peripheral oxygen saturation were evaluated after treatment on Day 1 (after a single dose) and Day 8 (after multiple doses).

Results: No significant differences in AHI were observed after single and multiple doses of LEM10 compared with PBO in participants with moderate to severe OSA (least-squares mean: single-dose LEM10, 41.7; PBO, 44.8; multiple-dose LEM10, 44.9; PBO, 45.7). In addition, there were no significant differences between treatments in peripheral oxygen saturation (least-squares mean: single-dose LEM10, 93.0; PBO, 93.1; multiple-dose LEM10, 93.1; PBO, 93.4). Further, there were no significant differences between treatments in percentage of total sleep time with peripheral oxygen saturation < 90%, < 85%, or < 80%. No significant differences were observed between treatments when AHI and peripheral oxygen saturation outcomes were analyzed by OSA severity. Altogether, 6/33 (18.2%) participants receiving LEM10, vs 3/33 (9.1%) PBO, reported treatment-emergent adverse events, mostly mild in severity.

Conclusions: LEM10 demonstrated respiratory safety and was well tolerated with single-dose and multiple-dose administration in participants with moderate to severe OSA. This suggests that LEM may be a treatment option for patients with OSA and comorbid insomnia.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: A Study to Evaluate the Respiratory Safety of Lemborexant in Adult and Elderly Participants With Moderate to Severe Obstructive Sleep Apnea and in Adult and Elderly Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease; URL: https://clinicaltrials.gov/ct2/show/NCT04647383; Identifier: NCT04647383.

Citation: Cheng JY, Lorch D, Lowe AD, et al. A randomized, double-blind, placebo-controlled, crossover study of respiratory safety of lemborexant in moderate to severe obstructive sleep apnea. J Clin Sleep Med. 2024;20(1):57-65.

Keywords: comorbid insomnia and obstructive sleep apnea; dual orexin receptor antagonist; insomnia; lemborexant; obstructive sleep apnea; respiratory.

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Conflict of interest statement

This work was supported by Eisai Inc. Medical writing assistance was provided by Luke Carey, PhD, CMPP, and Rency Mathew, PhD, of Envision Pharma Group, and was funded by Eisai Inc. D.L. is a paid clinical trial investigator for Apnimed Inc., Suven Life Sciences Ltd., Eisai Inc., Merck & Co., Pfizer, Jazz Pharmaceuticals, Aptinyx, Moderna, Inc., Lexicon Pharmaceuticals, Novartis, Takeda Pharmaceuticals, Sorrento Therapeutics, Lilly, Galapagos, and Sanofi. A.D.L. has received research support from AstraZeneca, Aventis Pharma Inc, Axsome Therapeutics, Boehringer Ingelheim, Brain Cells Inc., Cephalon Inc, Eisai Inc., Eli Lilly, Flamel Ireland Ltd, GlaxoSmithKline, Idorsia Pharmaceuticals, Lundbeck, Merck and Co Inc, Otsuka Pharmaceutical, and Sanofi-Aventis, and is on the speakers bureau of AstraZeneca, Eisai Inc, Eli Lilly and Company, Jazz Pharmaceuticals, Lundbeck, Otsuka Pharmaceutical, Paladin Inc., Sunovion, Valeant Ltd., and Wyeth Pharmaceuticals. N.U. has received lecture fees from Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Merck Sharp & Dohme, and Takeda Pharmaceutical Co., Ltd. M.M., J.Y.C., N.H., and D.S. are employees of Eisai Inc.

Figures

Figure 1
Figure 1. Study design.
EOS = end of study, FU = follow-up, LEM10 = lemborexant 10 mg, PBO = placebo, WO = washout.
See this image and copyright information in PMC

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