Effect of daridorexant on sleep and daytime functioning in older adults with insomnia disorder

Abstract: As insomnia affects elderly more than younger adults, therapeutic options with limited safety risks are needed to treat this patient group. We report elderly subgroup analyses from a Phase-3 trial with daridorexant. In a multi-center, double-blind trial (NCT03545191), adult (18–64y) and elderly (≥65y) patients with insomnia received daridorexant 25mg, 50mg or placebo every evening for 3 months. Efficacy endpoints included wake-after-sleep-onset (WASO), latency-to-persistent-sleep (LPS), subjective total sleep time (sTST), and daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire [IDSIQ] – sleepiness domain). Safety endpoints included treatment emergent adverse events (TEAE), AEs of special interest, and withdrawal effects. Of 930 patients, 364 (39.1%) were ≥65y: daridorexant 25mg (n=121), 50mg (n=121) and placebo (n=122). At Month 3, least-square mean of change from baseline for daridorexant 25mg and 50mg were: WASO -17.0 and -19.6 mins; LPS -7.8 and -14.9 mins; sTST 18.7 and 30.6 mins; IDSIQ sleepiness domain -0.6 and -2.6, respectively. TEAEs were similar across the groups (32.2%, 35.3%, and 31.1%; daridorexant 25mg, 50mg and placebo, respectively). Falls and dizziness, both of interest in elderly, were least frequent in the 50mg group. Compared to placebo, somnolence was as frequent for 50mg daridorexant while fatigue was more frequent in both daridorexant groups; incidence did not appear dose-related. AESI, of mild intensity, were reported in 2 patients ≥65y (one/daridorexant group). There was no evidence of withdrawal symptoms. Daridorexant is efficacious in the elderly population for improvements in sleep and daytime functioning. No safety concerns in this vulnerable population were identified at either dose.Short Description: The data from this study reports the elderly subgroup analyses from a Phase 3 trial with daridorexant. Daridorexant was shown to be efficacious in the elderly population with improvements in night-time symptoms and daytime functioning. Of note, no safety concerns in this population were identified at either evaluated dose.Name of Sponsoring Organization(s): Idorsia Pharmaceuticals Ltd