344 Daridorexant Improves Total Sleep Time (TST) in Insomnia Patients Without Altering the Proportion of Sleep Stages

Abstract

Abstract Introduction Daridorexant, a new dual orexin receptor antagonist, improved sleep parameters and daytime functioning in two pivotal Phase 3 trials in patients with insomnia (Trial-1, NCT03545191; Trial-2, NCT03575104); polysomnography data were collected at multiple timepoints from >1,800 patients. We report the effects of daridorexant on TST and sleep stages from both trials. Methods Eligible patients with insomnia (according to DSM-5) were randomized (1:1:1) in Trial-1 (N=930) to daridorexant 25mg, 50mg, or placebo and in Trial-2 (N=924) to daridorexant 10mg, 25mg, or placebo. Oral treatment was administered each night during a 3-month double-blind treatment period. Assessment of TST and sleep stages (non-rapid eye movement [NREM, N]1, N2, N3, REM), measured by polysomnography in sleep laboratory, was performed on two consecutive nights during single-blind placebo run-in (baseline) and Months 1 and 3 (M1 and M3) of double-blind treatment. Change from baseline in TST and sleep stages were exploratory endpoints in both trials. Data for M3 (mean ± standard deviation) are presented as change from baseline. Results Daridorexant dose-dependently increased TST(minutes) from baseline to M3, more than placebo, in Trial-1 (25mg, 55±56; 50mg, 61±53; placebo, 40±56) and Trial-2 (10mg, 37±57; 25mg, 50±53; placebo, 35±56). In both trials, sleep stage proportions were preserved from baseline to M3, with no relevant changes in any group. Baseline time spent in each sleep stage (% of TST) was consistent across groups in both trials (range across treatment groups in both trials: N1:11–13; N2:55–57; N3:11–14; REM:19–20). In Trial-1 (25mg/50mg/placebo), the change from baseline to M3 in % of TST spent in N1(-0.3±4.7/-0.2±5/0.1±5), N2(2±8/1±7/1±7), N3(-2±6/-2±6/-2±6), and REM(1±6/1±5/1±5) was low and numerically similar across treatments. In Trial-2, the change from baseline to M3 in % of TST spent in each sleep stage was consistent with Trial-1, with no effect of dose. Mean changes from baseline (% of TST) for each sleep stage appeared to be independent from increasing TST. Data for 25mg were consistent between trials. Conclusion Daridorexant at any dose, and each more than placebo, increased TST in a dose-dependent manner without affecting the proportion of all sleep stages in patients with insomnia. Support (if any) Funded by Idorsia Pharmaceuticals Ltd.