Daridorexant in severe obstructive sleep apnea: Effects on sleep-disordered breathing and sleep

To evaluate the effect of daridorexant on nighttime respiratory function and sleep in adults with severe obstructive sleep apnea (OSA) without insomnia.

This randomized, double-blind, placebo-controlled, two-period, crossover trial was conducted at a single sleep center in 16 adults (≥18 years) with severe OSA without insomnia. In each period, daridorexant 50 mg or placebo was administered every evening for 5 days. Primary and secondary endpoints were the treatment differences (daridorexant - placebo) for apnea/hypopnea index (AHI) and oxygen saturation (SpO2) during total sleep time (TST), respectively, after last dosing. A mean increase in AHI ≥10 events/h and mean decrease in nocturnal SpO2 ≤-2% were the minimum changes considered to be clinically meaningful negative effects. Other endpoints included TST, latency to persistent sleep (LPS), and wake after sleep onset (WASO).

Mean baseline AHI was 51.2 events/h (range 30.8, 82.2) and mean SpO2 during TST was 92.1% (range 88.5, 94.3). No clinically meaningful effect of daridorexant on AHI or SpO2 during TST was detected. Treatment differences were -3.7 events/h (one-sided 95% CI≤+4.2) and -0.12 % (one-sided 95% CI≥-0.6), respectively. Compared with placebo, daridorexant increased TST by 32.5 min (90% CI: 6.9, 58.2), associated with shorter LPS (-10.3 min [90% CI:-20.6, -0.02]) and a trend towards reduced WASO (-15.2 min [-31.2, 0.9]). Four adverse events were reported (daridorexant n=3; placebo n=1), all of mild intensity and none related to respiratory function.

Short-term treatment with daridorexant does not impair sleep-disordered breathing and may improve sleep in patients with severe OSA.

ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT05458193, NCT05458193.