Patricia Murphy1, Dinesh Kumar2, Gary Zammit3, Russell Rosenberg4, Margaret Moline2. 1. Formerly of Eisai Inc., Woodcliff Lake, New Jersey. 2. Eisai Inc., Woodcliff Lake, New Jersey. 3. Clinilabs Drug Development Corporation, New York, New York. 4. NeuroTrials Research Inc., Atlanta, Georgia.
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://clinicaltrials.gov/ct2/show/NCT03008447; Identifier: NCT03008447.
RCT Entities:
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://clinicaltrials.gov/ct2/show/NCT03008447; Identifier: NCT03008447.
Authors: Patricia Murphy; Margaret Moline; David Mayleben; Russell Rosenberg; Gary Zammit; Kate Pinner; Shobha Dhadda; Quan Hong; Luigi Giorgi; Andrew Satlin Journal: J Clin Sleep Med Date: 2017-11-15 Impact factor: 4.062
Authors: Jennifer L Schroeck; James Ford; Erin L Conway; Kari E Kurtzhalts; Megan E Gee; Krista A Vollmer; Kari A Mergenhagen Journal: Clin Ther Date: 2016-10-15 Impact factor: 3.393
Authors: Mikko Kärppä; Jane Yardley; Kate Pinner; Gleb Filippov; Gary Zammit; Margaret Moline; Carlos Perdomo; Yuichi Inoue; Kohei Ishikawa; Naoki Kubota Journal: Sleep Date: 2020-09-14 Impact factor: 5.849