Daridorexant, a 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). We report the effects of daridorexant on TST and sleep stages from both trials.
Eligible patients with insomnia (DSM-5 criteria) 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], N1, 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.
Daridorexant dose-dependently increased TST(minutes) from baseline to M3 versus 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. In Trial-1, the change from baseline to M3 in% of TST spent in N1-N3, and REM was low and numerically similar across treatments. In Trial-2, change from baseline to M3 in% of TST spent in each sleep stage was consistent with Trial-1, with no dose effect. Mean changes from baseline (% of TST) for each sleep stage appeared to be independent from increasing TST.
Daridorexant versus placebo increased TST in a dose-dependent manner without affecting the proportion of sleep stages in patients with insomnia.
Support: Idorsia Pharmaceuticals Ltd.
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