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

Abstract

Introduction Insomnia affects older adults more than younger adults, and comorbidities more prevalent in older populations can add to symptom burden and reduce therapeutic options. Drugs that improve insomnia symptoms with limited safety risks are needed to treat this patient group. We report older adult subgroup analyses from a Phase-3 registration trial with daridorexant. Methods In this multi-center, double-blind trial (NCT03545191), adults (18–64y) and older adults (≥65y) with insomnia were randomized (1:1:1) to receive oral daridorexant 25mg, 50mg or placebo every evening for 3 months. Month 3 endpoints were: change from baseline in polysomnography-measured wake-after-sleep-onset (WASO) and latency-to-persistent-sleep (LPS) (both primary endpoints), subjective total sleep time (sTST), and daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire [IDSIQ] – sleepiness domain; with a lower score indicating improved daytime functioning). Safety endpoints included treatment emergent adverse events (TEAE), AEs of special interest (AESI; symptoms related to excessive daytime sleepiness or complex sleep behavior, and suicidal ideation/self-injury) and withdrawal effects upon treatment cessation (assessed by the Benzodiazepine Withdrawal Symptom Questionnaire total score and relevant AEs). Results Of the 930 patients randomized, 364 (39.1%) were ≥65y: daridorexant 25mg (n=121), 50mg (n=121) and placebo (n=122). In this subgroup, at Month 3, the placebo-corrected least-square mean of change from baseline [95%CL] for daridorexant 25mg and 50mg were: WASO -17.0[-27.0,-7.0] and -19.6[-29.5,-9.7] mins; LPS -7.8[-15.2,-0.4] and -14.9[-22.3,-7.5] mins; sTST 18.7[4.1,33.2] and 30.6[16.1,45.2] mins; IDSIQ sleepiness domain -0.6[-2.2,0.9] and -2.6[-4.1,-1.0], all respectively. Conclusions Daridorexant is efficacious in the older adults for improvements in sleep and daytime functioning. No significant safety concerns in this vulnerable population were identified at either dose. This research was funded by Funded by Idorsia Pharmaceuticals Ltd. Fietze I, Bassetti C, Mayleben D, et al, 347. Daridorexant is Safe and Improves Both Sleep and Daytime Functioning in Elderly Patients with Insomnia, Sleep 2021; 44 (Suppl_2): A138-A139, https://doi.org/10.1093/sleep/zsab072.346 © Sleep Research Society 2021. Published by OUP on behalf of the Sleep Research Society. Insomnia affects older adults more than younger adults, and comorbidities more prevalent in older populations can add to symptom burden and reduce therapeutic options. Drugs that improve insomnia symptoms with limited safety risks are needed to treat this patient group. We report older adult subgroup analyses from a Phase-3 registration trial with daridorexant. In this multi-center, double-blind trial (NCT03545191), adults (18–64y) and older adults (≥65y) with insomnia were randomized (1:1:1) to receive oral daridorexant 25mg, 50mg or placebo every evening for 3 months. Month 3 endpoints were: change from baseline in polysomnography-measured wake-after-sleep-onset (WASO) and latency-to-persistent-sleep (LPS) (both primary endpoints), subjective total sleep time (sTST), and daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire [IDSIQ] – sleepiness domain; with a lower score indicating improved daytime functioning). Safety endpoints included treatment emergent adverse events (TEAE), AEs of special interest (AESI; symptoms related to excessive daytime sleepiness or complex sleep behavior, and suicidal ideation/self-injury) and withdrawal effects upon treatment cessation (assessed by the Benzodiazepine Withdrawal Symptom Questionnaire total score and relevant AEs). Of the 930 patients randomized, 364 (39.1%) were ≥65y: daridorexant 25mg (n=121), 50mg (n=121) and placebo (n=122). In this subgroup, at Month 3, the placebo-corrected least-square mean of change from baseline [95%CL] for daridorexant 25mg and 50mg were: WASO -17.0[-27.0,-7.0] and -19.6[-29.5,-9.7] mins; LPS -7.8[-15.2,-0.4] and -14.9[-22.3,-7.5] mins; sTST 18.7[4.1,33.2] and 30.6[16.1,45.2] mins; IDSIQ sleepiness domain -0.6[-2.2,0.9] and -2.6[-4.1,-1.0], all respectively. Daridorexant is efficacious in the older adults for improvements in sleep and daytime functioning. No significant safety concerns in this vulnerable population were identified at either dose.