Russell Rosenberg1, Motohiro Ozone2, Margaret Moline3, Naohisa Uchimura2, Hiroshi Hiejima2, Kenta Murotani4, Takehiro Taninaga5, Jocelyn Cheng3, Dinesh Kumar3
1Neurotrials Research, 2Kurume University School of Medicine, 3Eisai Inc., 4Kurume University, 5Eisai Co., Ltd.
Objective:
Evaluate the success rate of direct transitioning from Z-drugs to a competitive dual orexin receptor antagonist, lemborexant (LEM), in subjects with insomnia who were dissatisfied with their current treatment in terms of effectiveness and/or tolerability.
Background:
While switching medications for insomnia occurs frequently in clinical practice, few clinical studies have assessed transition between drug classes. LEM is approved over 10 countries to treat adults with insomnia. Two open-label studies (United States: E2006-A001-312, Study 312, NCT04009577; Japan: E2006-M081-401, Study 401, NCT04742699) evaluated success rates of directly transitioning from Z-drugs to LEM under a prespecified dosing paradigm.
Design/Methods:
Studies 312 and 401 included a 3-week and 2-week Screening Period, respectively (subjects continued zolpidem [ZOL] in Study 312 or Z-drug monotherapy [ZOL, zopiclone, or eszopiclone] in Study 401), 2-week Titration Period (TITR), 12-week Extension Period (not reported), and 4-week Follow-up Period. Study 312 had Cohort 1: Intermittent (3-4 nights/week) ZOL users and subjects with 1 week each of intermittent and frequent ZOL usage; all started TITR with LEM 5 mg (LEM5). Cohort 2 included frequent (≥5 nights/week) ZOL users and were randomized 1:1 to LEM5 or LEM 10 mg. In Study 401, all subjects started with LEM5 during TITR. The primary endpoint in both studies was the proportion of subjects who successfully transitioned to LEM at the end of TITR. Safety evaluations were conducted.
Results:
In Study 312, most subjects (overall n=43/53, 81.1%; Cohort 1, n=10; Cohort 2, n=43) transitioned from ZOL to LEM at the end of TITR, regardless of prior ZOL use. In Study 401, 92% of subjects (n=23/25; n=6 ZOL, n=1 zopiclone, n=18 eszopiclone) showed successful transition to LEM. No new safety signals emerged during transitioning.
Conclusions:
Both studies indicate that adults with insomnia can successfully transition directly from a Z-drug to LEM. LEM was generally well tolerated.