Safety of lemborexant versus placebo and zolpidem: effects on auditory awakening threshold, postural stability, and cognitive performance in healthy older participants in the middle of the night and upon morning awakening
Patricia Murphy, Dinesh Kumar, Gary Zammit, Russell Rosenberg, Margaret Moline, Patricia Murphy, Dinesh Kumar, Gary Zammit, Russell Rosenberg, Margaret Moline
Abstract
Study objectives: Our aim was to evaluate the effect of lemborexant versus zolpidem tartrate extended release 6.25 mg (ZOL) or placebo (PBO) on postural stability, auditory awakening threshold (AAT), and cognitive performance (cognitive performance assessment battery [CPAB]).
Methods: Healthy women (≥ 55 years) and men (≥ 65 years) were randomized, double-blind, to 1 of 4-period, single-dose crossover sequences, starting with lemborexant 5 mg (LEM5), 10 mg (LEM10), ZOL, or PBO. A ≥ 14-day washout followed all 4 treatments. Assessments were middle-of-the-night (MOTN) change from baseline in postural stability (primary prespecified comparison: LEM vs ZOL), AAT, absolute AAT, and CPAB for LEM5 and LEM10 versus ZOL and PBO; and morning change from baseline in postural stability and CPAB for LEM5 and LEM10 versus ZOL and PBO. Change from baseline measures were time-matched to a baseline night/morning when no study drug was administered.
Results: MOTN: Mean MOTN change from baseline in body sway was significantly higher for ZOL versus both lemborexant doses. There were no differences among the treatments regarding decibels required to awaken a participant. LEM5 was not statistically different from PBO on any CPAB domain; LEM10 and ZOL showed poorer performance on some tests of attention and/or memory. Morning: Body sway and cognitive performance following LEM5 or LEM10 did not differ from PBO; body sway was significantly higher for ZOL than PBO. Rates of treatment-emergent adverse events were low; there were no serious adverse events.
Conclusions: Lemborexant causes less postural instability than a commonly used sedative-hypnotic and does not impair the ability to awaken to auditory signals.
Clinical trials registration: Registry: ClinicalTrials.gov; Name: Crossover Study to Evaluate the Effect of Lemborexant Versus Placebo and Zolpidem on Postural Stability, Auditory Awakening Threshold, and Cognitive Performance in Healthy Subjects 55 Years and Older; URL: https://ichgcp.net/clinical-trials-registry/NCT03008447; Identifier: NCT03008447.
Keywords: attention; auditory awakening; lemborexant; memory; older adults; postural stability; zolpidem.
Conflict of interest statement
All authors have seen and approved the final manuscript. This study was sponsored by Eisai Inc. Medical writing assistance was provided by Samantha Forster, PhD, CMPP, of ProScribe, part of the Envision Pharma Group. Envision Pharma’s services complied with international guidelines for Good Publication Practice (GPP3). Patricia Murphy is a former employee of Eisai Inc. Dinesh Kumar and Margaret. The authors contributed to this paper as follows: Patricia Murphy, as Study Director, had full access to all study data and takes responsibility for all aspects of the study, including the integrity of the data and the accuracy of the data analysis. Patricia Murphy and Margaret Moline supervised the study. Patricia Murphy, Margaret Moline, Gary Zammit, and Russell Rosenberg were involved in the study concept and design. All authors were involved in the analysis and interpretation of data, the drafting of the manuscript, and in critical revision of the manuscript for important intellectual content. Dinesh Kumar conducted the statistical analysis; Patricia Murphy and Margaret Moline obtained funding. All authors have seen and approved the final manuscript. Moline are current employees of Eisai Inc. Gary Zammit is an employee and shareholder of Clinilabs Drug Development Corporation; has ownership interest in the Sleep Disorders Institute and Home Sleep and Respiratory Care; has served as a consultant for Eisai Inc., Janssen Pharmaceutical, Purdue, and Takeda; and has served on the speakers bureau for Merck. Russell Rosenberg has received grant/research support from Actelion Pharmaceuticals, Eisai Inc., Flamel Pharmaceuticals, Jazz Pharmaceuticals, Merck, and Philips Respironics.
© 2020 American Academy of Sleep Medicine.
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Source: PubMed