Effect Of Multiple-Dose Treatment With Daridorexant On Nighttime Respiratory Function In Patients With Mild And Moderate Obstructive Sleep Apnea (Osa)

Former classes of sleep medications may affect nighttime respiratory function. Daridorexant is a dual orexin receptor antagonist developed for the treatment of insomnia. This randomized, double-blind, placebo-controlled, two-period, crossover study evaluated whether multiple-dose (5 nights) administration of the highest phase 3 dose of 50 mg daridorexant produced a clinically meaningful effect on apnea/hypopnea index (AHI) during total sleep time (TST), i.e., treatment difference (daridorexant–placebo) ≥ 5 events/h in patients with mild and moderate OSA. AHI and oxygen saturation (SaO2) during non-REM and REM sleep as well as safety and tolerability were also evaluated. Of 28 subjects enrolled, 25 (OSA intensity: 15 mild–10 moderate, mean [standard deviation] AHI: 16.3 [8.2]events/h) completed the study and were included in the analysis. After multiple dosing of 50 mg daridorexant, mean AHI during TST was not different from placebo (0.74 [90% CI: -1.43–2.92]events/h), indicating that daridorexant has no clinically meaningful effect on AHI. No effect was observed on SaO2 during TST (mean treatment difference of -0.18 [90% CI: -0.70–0.34]%). Evaluation of AHI and SaO2 during non-REM and REM sleep also showed no differences between daridorexant and placebo. No SAEs occurred. Overall, 9/28 subjects (32.1%) reported at least 1 treatment-emergent adverse event, none of them related to respiratory function. Overall, no effects on vital signs, ECG, or laboratory variables were detected after daridorexant administration. Our results show that daridorexant does not impair nighttime respiratory function in patients with mild and moderate OSA.