3052 Efficacy and safety of daridorexant in patients >65 years 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. We report older subgroup analyses from a Phase-3 registration trial with daridorexant. Methods In this multi-centre, double-blind trial (NCT03545191), adults 18–64y and ≥ 65y with insomnia were randomised (1:1:1) to receive oral daridorexant 25 mg, 50 mg 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. Safety endpoints included treatment emergent adverse events (TEAE), AEs of special interest (AESI) (and withdrawal effects upon treatment cessation. Results Of the 930 patients randomised, 364 (39.1%) were ≥ 65y: daridorexant 25 mg (n = 121), 50 mg (n = 121) and placebo (n = 122). In this subgroup, at Month 3, the placebo-corrected change from baseline [95%CL] for daridorexant 25 mg and 50 mg 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], respectively. TEAEs were reported in 32.2%, 35.3%, and 31.1% of patients ≥65y in the 25 mg, 50 mg and placebo groups, respectively. Falls (n = 1,1,4 for 25 mg, 50 mg, placebo, respectively) and dizziness (n = 4,1,1), were least frequent in the 50 mg group. Compared to placebo, somnolence was as frequent for 50 mg daridorexant (n = 6,1,1) while fatigue was more frequent in both daridorexant groups (n = 4,3,1); incidence did not appear dose-related. AESI, of mild intensity, were reported in 2 patients ≥65y (one in each daridorexant group). There was no evidence of withdrawal symptoms. Conclusions Daridorexant is efficacious in adults >65 years for improvements in sleep and daytime functioning. No safety concerns in this vulnerable population were identified at either dose. Support: Funded by Idorsia Pharmaceuticals Ltd