0547 Vil-tra

Abstract Introduction Obstructive sleep apnea (OSA) poses deleterious health consequences. Pharmacotherapy is a promising alternative to the current standard of care; recently, a combination of the noradrenergic atomoxetine, with the antimuscarinic aroxybutynin reduced OSA severity. Atomoxetine has also proven to be efficacious in combination with the anti-depressant trazodone. However, atomoxetine is wake-promoting especially in the subgroup of poor CYP2D6 metabolizers, which may contribute to apnea cycling and reduced drug tolerability. Therefore, we investigated the effect of a potentially more manageable noradrenergic, viloxazine, with and without trazodone, on OSA severity. Methods Twenty-five patients with OSA (apnea-hypopnea index [AHI4] 10-45) aged 18-75 years were randomized to viloxazine 500mg, viloxazine/trazodone 500/75mg or placebo according to a double-blind, placebo-controlled, crossover study. Drugs were taken before bed, for two weeks each period, with a first week of run-in (viloxazine 200mg and/or trazodone 50mg) and a 1-week washout between periods. In-laboratory polysomnography was performed at the end of each crossover period. Mixed model analyses compared the effect of the combination vs. placebo on AHI4 (primary outcome), hypoxic burden, total sleep time (TST) and wake-after-sleep-onset (WASO; secondary outcomes). Tertiary analyses explored differences between the parameters above across all treatment arms, in addition to sleep architecture and subjective outcomes. Safety endpoints were also assessed. Results Viloxazine-trazodone reduced AHI4 (13 [6, 19] events/h] vs. placebo (53 %min/h, 28 events/h) and hypoxic burden (mean reduction (95% CI): 26 [14, 34] %min/h). The combination reduced TST [37 [13, 61] min) and increased WASO (26 [2, 49] min) vs. placebo. Viloxazine alone had a similar effect on OSA severity vs. placebo. However, its impact on sleep quality (TST -61 [-85, -37] min; WASO 41 [18, 64]) was accentuated vs. placebo. Both viloxazine and the combination worsened patient-reported outcomes vs. placebo; these changes seemed more pronounced on viloxazine alone vs. placebo. 6 patients terminated the study early, 5 due to adverse events. Commonly reported adverse events were insomnia, constipation, headache, and xerostomia. Both treatments slightly increased heart rate. Conclusion Viloxazine-trazodone combination may reduce OSA severity. Potential deleterious effects of viloxazine on sleep quality appear partly attenuated by concurrent trazodone. Support (if any) This study was funded by Apnimed.