Daridorexant in Japanese patients with insomnia disorder: A phase 3, randomized, double-blind, placebo-controlled study.

Objective: This Phase 3 double-blind, placebo-controlled study evaluated the efficacy and safety of daridorexant in Japanese patients with insomnia disorder.
Patients/methods: 490 patients with insomnia disorder from 95 sites in Japan were randomized to daridorexant 50 mg (n = 163), 25 mg (n = 163) or placebo (n = 164) for 4 weeks, followed by a 7-day placebo run-out and a 30-day safety follow-up. The primary efficacy endpoints, in hierarchical order, were change from baseline at Week 4 in subjective total sleep time (sTST) and subjective latency to sleep onset (sLSO), for daridorexant 50 mg vs placebo. sTST and sLSO were also evaluated (secondary endpoints) for daridorexant 25 mg vs placebo. Safety endpoints included adverse events and next-morning sleepiness (Visual Analog Scale, VAS).
Results: Daridorexant 50 mg significantly increased sTST and decreased sLSO versus placebo at Week 4 (least-squares mean difference [LSMD]: sTST 20.3 min [95 % CI 11.4, 29.2] p < 0.001; sLSO -10.7 min [-15.8, -5.5] p < 0.001). Daridorexant 25 mg also significantly improved both endpoints versus placebo (LSMD: sTST 9.2 min [0.3, 18.1] p = 0.042; sLSO -7.2 min [-12.3, -2.0] p = 0.006). Overall incidence of adverse events was similar across groups (50 mg: 22 %; 25 mg: 18 %; placebo 23 %); somnolence, the most common event, increased with increasing dose (50 mg: 6.8 %; 25 mg: 3.7 %; placebo 1.8 %). However, daridorexant did not increase VAS next-morning sleepiness. No rebound or withdrawal-related symptoms were observed after treatment discontinuation.
Conclusions: In Japanese patients with insomnia disorder, daridorexant (25 and 50 mg) was well tolerated and significantly improved subjective sleep outcomes, with no evidence of residual effects.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors report financial support, administrative support, and writing assistance were provided by Nxera Pharma Japan Co., Ltd. All authors report financial support was provided by Mochida Pharmaceutical Co Ltd. Naohisa Uchimura reports a relationship with Eisai Co Ltd that includes: speaking and lecture fees. Naohisa Uchimura reports a relationship with MSD KK that includes: speaking and lecture fees. Mitsutaka Taniguchi reports a relationship with Eisai Co Ltd that includes: consulting or advisory and speaking and lecture fees. Mitsutaka Taniguchi reports a relationship with Taisho Pharmaceutical Holdings Co Ltd that includes: consulting or advisory and speaking and lecture fees. Mitsutaka Taniguchi reports a relationship with Aculys Pharma, LLC. That includes: consulting or advisory and speaking and lecture fees. Mitsutaka Taniguchi reports a relationship with MSD KK that includes: consulting or advisory and speaking and lecture fees. Yasunori Oka reports a relationship with Astellas Pharma Inc that includes: speaking and lecture fees. Yasunori Oka reports a relationship with Eisai Co Ltd that includes: speaking and lecture fees. Yasunori Oka reports a relationship with MSD KK that includes: speaking and lecture fees. Yasunori Oka reports a relationship with Nobelpharma Co Ltd that includes: speaking and lecture fees. Osamu Togo reports a relationship with Nxera Pharma Japan Co., Ltd that includes: employment. Makoto Uchiyama reports a relationship with Nxera Pharma Japan Co., Ltd that includes: consulting or advisory. Makoto Uchiyama reports a relationship with LIXIL Corporation that includes: consulting or advisory. Makoto Uchiyama reports a relationship with Taisho Pharmaceutical Co Ltd that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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