Late Breaking Abstract - A randomized, double-blind, placebo controlled, dose-finding trial of sulthiame in obstructive sleep apnea

<bold>Objectives:</bold> Drug treatment has emerged as a method with high compliance and good tolerability in obstructive sleep apnea (OSA). The carbonic anhydrase inhibitor sulthiame (STM) had a favorable safety profile and effectively reduced apneas in a previous phase 2b trial. <bold>Methods:</bold> A double-blind, randomized, placebo-controlled, multi-center dose-ranging study in OSA patients not accepting or tolerating CPAP or oral splints. Three doses of STM and placebo were evaluated by polysomnography (twice at baseline and once after 4 and 12 weeks of STM at target dose (week 15). A total of 298 subjects, 26,2% female, age 56,1±10,5 years, BMI 29,1±3,3 kg/m² and AHI3a 29,0±9,5 n/h were randomized to 100 mg (N=74), 200 mg (N=74), 300 mg (N=75) STM or placebo (N=75). <bold>Results:</bold> The primary efficacy endpoint, AHI3a change from baseline at week 15 was met, -17,8% at 100mg (p<0,05), - 34,8% at 200mg (p<0,0001), and -39,9% at 300mg (p<0,0001). There was a placebo adjusted dose-dependent reduction of AHI4 (apnea/hypopnea with ≥4% O2 desaturation) by 47.1 % at week 15. STM improved mean overnight O2 saturation by 0,95% and 0,87% at week 15 (200mg and 300mg respectively; p<0,0001). Total arousal index and sleep quality improved and the effects on sleep macro-structure were neutral. The ESS score was reduced in sleepy patients (ESS≥11). AEs (paresthesia, headache, fatigue, and nausea) were mostly mild-to-moderate and dose dependent without cardiovascular safety issues. <bold>Conclusions:</bold> STM, in the evaluated dose range, provides a consistent reduction of sleep disordered breathing and improvement of sleep quality, hypoxia, and daytime sleepiness. STM is a promising candidate for drug therapy in OSA.