Effect of daridorexant on wakefulness throughout the night: Post-hoc analysis of a randomised, double-blind, active reference (zolpidem) study in patients with insomnia disorder

Introduction Daridorexant, a dual orexin receptor antagonist DORA which works by selectively reducing the orexin-induced wake signalling, has been shown to induce a dose-dependent reduction in wake time after sleep onset WASO in patients with insomnia disorder (Dauvilliers et al. Ann Neurol 2020; 87 347–356). Objectives This exploratory analysis examined the efficacy of daridorexant in reducing the duration of awakenings in each quarter of the night, when compared to placebo and to the GABA-receptor agonist zolpidem, which induces sleep through widespread CNS sedation. Methods This was a multi-centre, double-blind trial (NCT02839200), including adult (18–64y) patients with insomnia randomized (1:1:1:1:1:1) to placebo, daridorexant (5, 10, 25, or 50mg), or zolpidem (10mg) for 30 days. Polysomnography PSG-determined WASO was evaluated using descriptive statistics by quarter of the night (Q1–Q4) i.e. every 2 hours over 8 hours at Days 1 Days 15 Q4: –17.51 min versus –7.81 min). Similar effects were seen at Days 15 & 16, and Days 28 & 29. Image 1: Conclusions In patients with insomnia disorder, daridorexant reduces the duration of awakenings throughout the entire night, including the last two quarters. Disclosure of Interest B. Steiniger-Brach Employee of: Idorsia Pharmaceuticals, O. Briasoulis Employee of: Idorsia Pharmaceuticals, A. Olivieri Employee of: Idorsia Pharmaceuticals, S. Pain Employee of: Idorsia Pharmaceuticals, L. Palagini Consultant of: Bruno, Fidia, Idorsia Pharmaceuticals, Pfizer, Sanofi, Pharmanutra, Neopharmed Gentili, D. Kunz Consultant of: Austrian Association of Skiing (ÖSV), Idorsia Pharmaceuticals, Speakers bureau of: AbbVie, Idorsia Pharmaceuticals, German Ministry for Economy (BMWi), Austrian Association of Skiing (ÖSV), P.-A. Geoffroy Consultant of: Apneal, Arrow, Biocodex, Dayvia, Di&Care, Idorsia Pharmaceuticals, Janssen-Cilag, Jazz pharmaceuticals, Myndblue, Mysommeil, Posos, ResilEyes, Withings, Speakers bureau of: Biocodex, Bioprojet, Ibsa, Idorsia Pharmaceuticals, Janssen-Cilag, Isis Medical, Jazz pharmaceuticals, Lundbeck, MySommeil, Withings.