Effects of daridorexant on sleep architecture in Japanese patients with insomnia disorder: analysis of a phase II randomized controlled trial

Abstract While daridorexant, a dual orexin receptor antagonist (DORA), demonstrated dose-dependent improvements in sleep parameters in a Japanese Phase II trial, its effects on sleep architecture remain incompletely characterized. This secondary analysis examined daridorexant’s effects on sleep fragmentation and architecture in Japanese patients with insomnia disorder. Forty-seven Japanese patients with insomnia (mean age 50.4 ± 8.0 years) underwent 10 nights of polysomnographic (PSG) recordings in a randomized protocol (baseline, placebo, daridorexant 10 mg, 25 mg, 50 mg; 2 nights each). Key parameters included latency to persistent sleep (LPS), total sleep time (TST), wake after sleep onset (WASO), sleep stage durations, and the number of persistent awakenings (NAW). The 8-hour recording was divided into quarters for temporal analysis. Dose-response trends were assessed using Jonckheere-Terpstra tests. Significant dose-response relationships were observed for LPS ( P = 0.004), TST ( P < 0.001), WASO ( P < 0.001), and NAW ( P = 0.004). Changes from baseline showed dose-dependent reductions in N1 time ( P = 0.006) and increases in N2 ( P = 0.049), N3 ( P = 0.050), and REM sleep times ( P < 0.001). Quartile analysis revealed a significant reduction in NAW in the first quarter with 50 mg ( P = 0.012) and a significant increase in REM sleep in the first and fourth quarters with 25 mg and 50 mg ( P < 0.05). Daridorexant dose-dependently improves sleep architecture by reducing fragmentation and enhancing deeper NREM and REM sleep. Temporal analysis demonstrated sustained effects throughout the night with REM sleep enhancement persisting through the final quarter. These findings suggest restoration of natural sleep architecture supporting daridorexant’s potential as a comprehensive sleep-promoting agent.