Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind, Placebo-Controlled Study

Abstract

<div class="section"> <a class="named-anchor" id="d12990925e257"> <!-- named anchor --> </a> <h5 class="section-title" id="d12990925e258">Study Objectives:</h5> <p id="d12990925e260">To identify dose(s) of lemborexant that maximize insomnia treatment efficacy while minimizing next-morning residual sleepiness and evaluate lemborexant effects on polysomnography (PSG) measures (sleep efficiency [SE], latency to persistent sleep [LPS], and wake after sleep onset [WASO]) at the beginning and end of treatment. </p> </div><div class="section"> <a class="named-anchor" id="d12990925e262"> <!-- named anchor --> </a> <h5 class="section-title" id="d12990925e263">Methods:</h5> <p id="d12990925e265">Adults and elderly subjects with insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition were enrolled in a multicenter, randomized, double-blind, placebo-controlled, Bayesian, adaptive, parallel-group study, receiving lemborexant (1, 2.5, 5, 10, 15, 25 mg) or placebo for 15 nights. Efficacy assessments included a utility function that combined efficacy (SE) and safety (residual morning sleepiness as measured by Karolinska Sleepiness Scale [KSS]), PSG measures, and sleep diary. Safety assessments included KSS, Digit Symbol Substitution Test, computerized reaction time tests, and adverse events (AEs). </p> </div><div class="section"> <a class="named-anchor" id="d12990925e267"> <!-- named anchor --> </a> <h5 class="section-title" id="d12990925e268">Results:</h5> <p id="d12990925e270">A total of 616 subjects were screened; 291 were randomized. Baseline characteristics were similar between lemborexant groups and placebo (∼63% female, median age: 49.0 years). The study was stopped for early success after the fifth interim analysis when the 15-mg dose met utility index/KSS criteria for success; 3 other doses also met the criteria. Compared with placebo, subjects showed significant improvements in SE, subjective SE, LPS, and subjective sleep onset latency at the beginning and end of treatment for lemborexant doses ≥ 5 mg ( <i>P</i> &lt; .05). WASO and subjective WASO showed numerically greater improvements for doses &gt; 1 mg. AEs, mostly mild to moderate, included dose-related somnolence. </p> </div><div class="section"> <a class="named-anchor" id="d12990925e275"> <!-- named anchor --> </a> <h5 class="section-title" id="d12990925e276">Conclusions:</h5> <p id="d12990925e278">Lemborexant doses ranging from 2.5–10 mg provided efficacy for the treatment of insomnia while minimizing next-morning residual sleepiness. </p> </div><div class="section"> <a class="named-anchor" id="d12990925e280"> <!-- named anchor --> </a> <h5 class="section-title" id="d12990925e281">Clinical Trial Registration:</h5> <p id="d12990925e283">Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Bayesian Adaptive Randomization Design, Dose Response Study of the Efficacy of E2006 in Adults and Elderly Subjects With Chronic Insomnia; URL: <a data-untrusted="" href="https://clinicaltrials.gov/ct2/show/NCT01995838" id="d12990925e285" target="xrefwindow">https://clinicaltrials.gov/ct2/show/NCT01995838</a>; Identifier: NCT01995838 </p> </div><div class="section"> <a class="named-anchor" id="d12990925e288"> <!-- named anchor --> </a> <h5 class="section-title" id="d12990925e289">Citation:</h5> <p id="d12990925e291">Murphy P, Moline M, Mayleben D, Rosenberg R, Zammit G, Pinner K, Dhadda S, Hong Q, Giorgi L, Satlin A. Lemborexant, a dual orexin receptor antagonist (DORA) for the treatment of insomnia disorder: results from a Bayesian, adaptive, randomized, double-blind, placebo-controlled study. <i>J Clin Sleep Med.</i> 2017;13(11):1289–1299. </p> </div>