Efficacy and safety of lemborexant in adults with insomnia: comparing Japanese and non-Japanese subgroups from the global, phase 3, randomized, double-blind, placebo-controlled SUNRISE 2 study

Abstract

Study objective: Whether there are racial differences in the efficacy/safety of hypnotics has not been sufficiently investigated. We aimed to evaluate the efficacy/safety of lemborexant 5 mg and lemborexant 10 mg vs placebo once daily in a subset of Japanese patients with insomnia and to compare the results with those of non-Japanese patients.

Methods: This subanalysis reports the results of the first 6 months (period 1, placebo-controlled) of SUNRISE 2, a 12-month, global, randomized, double-blind, phase 3 study. Changes in patient-reported sleep onset latency, patient-reported sleep efficiency, and patient-reported wake after sleep onset with lemborexant 5 mg or lemborexant 10 mg vs placebo were evaluated. Treatment-emergent adverse events were evaluated for safety.

Results: In total, 949 patients were randomized (Japanese, n = 161; non-Japanese, n = 788). Groups were balanced at baseline except for the male/female ratio (P = .0002) and body mass index (P < .0001) in the Japanese vs non-Japanese subgroups. Overall, the efficacy and safety of lemborexant were similar between subgroups. In the Japanese subgroup, the subjective sleep onset latency change from baseline was significant after 7 nights and 6 months with lemborexant 10 mg vs placebo, the subjective sleep efficiency change from baseline was significant after 7 nights with lemborexant 10 mg vs placebo, and the subjective wake after sleep onset change from baseline was significant at 6 months with lemborexant 5 mg vs placebo. The incidence and severity of treatment-emergent adverse events were consistent between both subgroups.

Conclusions: Lemborexant 5 mg and 10 mg improved sleep onset and sleep maintenance over 6 months and was well-tolerated in both the Japanese and non-Japanese patients. The safety profiles of lemborexant 5 mg and 10 mg were consistent between the subgroups.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: Long-term Study of Lemborexant in Insomnia Disorder (SUNRISE 2); URL: https://ichgcp.net/clinical-trials-registry/NCT02952820; Identifier: NCT02952820; and Registry: ClinicalTrialsRegister.eu; Identifier: 2015-001463-39.

Keywords: Japan; chronic insomnia disorder; clinical trial; lemborexant; sleep disorder; subgroup analysis.

Conflict of interest statement

All authors have seen and approved the manuscript. This study was funded by Eisai, Inc. Y.I. has received grants and/or personal fees from Eisai, MSD, and Takeda Pharmaceutical in relation to the submitted work and has received grants or personal fees from Alfresa Pharma, Phillips, and Koike Medical and funding for clinical trials from Astellas Pharmaceutical and Janssen Pharmaceutical outside of the submitted work. T.W., S.T., T.T., K.I., N.K., J.Y., and M.M. are full-time employees of Eisai.

© 2021 American Academy of Sleep Medicine.

Figures

Figure 1. Study design overview.

BL = baseline, EOS = end of study, LEM5 = lemborexant 5 mg, LEM10 = lemborexant 10 mg, PBO = placebo, SCR = screening.

Figure 2. Patient disposition (Japanese and non-Japanese patients).

LEM5 = lemborexant 5 mg, LEM10 = lemborexant 10 mg, PBO = placebo.

Figure 3. Difference between PBO vs LEM5/LEM10 in (A) sSOL and (B) sWASO changes from baseline in Japanese and non-Japanese subgroups.

CI = confidence interval, LEM = lemborexant, LEM5 = lemborexant 5 mg, LEM10 = lemborexant 10 mg, LSGM = least-squares geometric mean, LS mean = least-squares mean, PBO = placebo; sSOL = subjective sleep onset latency, sWASO = subjective wake after sleep onset.