357 Daridorexant Does Not Impair Respiratory Function in Patients with Mild/Moderate Obstructive Sleep Apnea Irrespective of Severity. (3rd May 2021) - Boof, Marie-Laure
Abstract: Introduction: Daridorexant is a dual orexin receptor antagonist developed for the treatment of insomnia. The effect of the highest phase-3 dose of 50 mg daridorexant on nighttime respiratory function was evaluated in patients with mild/moderate obstructive sleep apnea (OSA). This study showed that repeated doses of daridorexant had no clinically meaningful effect on nighttime respiration (i.e., apnea-hypopnea index [AHI] and peripheral oxygen saturation [SpO2]). In the same study, other relevant respiratory endpoints were evaluated. Methods: In this randomized, double-blind, placebo-controlled, two-period, crossover study, daridorexant or placebo was administered in each period once daily for 5 consecutive nights to 28 patients. Treatment differences (daridorexant – placebo) for total number and mean/longest duration of apneas and hypopneas as well as mean and lowest SpO2 during apnea/hypopnea events in Night 5 were explored using linear mixed-effects modeling. Treatment differences for the above-mentioned endpoints versus AHI during TST at baseline (i.e., OSA severity) was analyzed by linear regression using least square approach. Results: Of 28 patients enrolled, 25 completed the study and were included in the analysis (n=15/10 with mild/moderate OSA; mean [standard deviation, SD] AHI: 16.3 events/h [8.2]). Compared to placebo, daridorexant increased mean duration of TST and accordingly to a not statistically significant extent the mean number of apneas + hypopneas by 16.4 events (n=103 versus 86.2; 90% confidence interval [CI]: -0.4–33.2]) without difference in mean [SD] AHI between daridorexant (15.1 events/h [7.9] and placebo (14.2 [7.7]). No treatment difference was detected for mean (0.0 sec [-2.6–2.7]) or longest (0.8 sec [-8.9–10.5]) duration of apneas nor for mean (0.2 sec [-2.2–2.5]) or longest (8.3 sec [6.4–23.1]) duration of hypopneas. No treatment difference was observed for mean (0.3% [-0.2–2.1]) and lowest (0.9% [0.3–2.1]) SpO2 during apnea/hypopnea events. Treatment differences for any of the evaluated endpoints did not significantly correlate with AHI at baseline as a marker of OSA severity (r2 ≤ 0.09). Conclusion: Daridorexant can safely be administered to patients with mild/moderate OSA as treatment differences for respiratory-related endpoints were not of statistical significance and independent of disease severity in the studied population. Support (if any): Funded by Idorsia Pharmaceuticals Ltd.