Efficacy and safety of daridorexant for the treatment of insomnia disorder in women of menopausal transition age: Insights from a randomized controlled trial

Abstract

Objectives: To evaluate the efficacy and safety of daridorexant in women aged 47–55 years with insomnia disorder, an age group representative of the menopause transition. Study design: In this randomized, double-blind, placebo-controlled study (NCT03545191), conducted in 10 countries between May 2018 and May 2020, 930 patients with insomnia disorder were randomized using interactive response technology (1:1:1) to receive a single film-coated tablet of daridorexant 25 mg, 50 mg, or placebo every evening for 3 months. Subgroup analyses were performed among the 117 women aged 47–55 (25 mg n = 43; 50 mg n = 35; placebo n = 39). Main outcome measures: Efficacy endpoints included change from baseline to Month 3 of treatment in polysomnography-measured wake after sleep onset (WASO) and latency to persistent sleep (LPS), self-reported total sleep time (sTST), and insomnia-related daytime impairment, as recorded on the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Safety endpoints included adverse events and score on a visual analog scale for morning sleepiness. Efficacy was analyzed in all randomized subjects, and safety in all who received at least one treatment dose. Results: At Month 3, daridorexant 50 mg vs placebo decreased WASO and LPS by a least-squares mean (LSM) of 13.8 min (95 % CI -29.0, 1.4) and 14.7 min (−30.0, 0.6) respectively, increased sTST by an LSM of 21.8 min (−3.9, 47.4) and decreased (improved) IDSIQ total score by an LSM of 4.1 (−14.4, 6.3). No marked deviations from the effect in the overall population were observed. The incidence of somnolence/fatigue was low and comparable across groups. Morning sleepiness improved in all groups. Conclusions: These analyses suggest that daridorexant 50 mg provides benefit in sleep outcomes and daytime functioning in women aged 47–55 with insomnia disorder. Daridorexant 50 mg is well tolerated in this population, with no increased risk of next-morning sleepiness or somnolence. ClinicalTrials.gov identifier: NCT03545191.