0451 Dronabinol Plus Acetazolamide for the Treatment of Obstructive Sleep Apnoea: A Proof of Concept and Mechanistic Exploration Study

Abstract Introduction Current treatments for obstructive sleep apnoea (OSA) typically target the anatomical pathophysiological endotype and are either not tolerated or effective in a significant proportion of patients. Pharmaceuticals may provide an alternative therapeutic option address some all remaining endotypes (loop gain, muscle compensation arousal threshold). This randomised, double-blind, placebo-controlled, cross-over study examined effect combination acetazolamide dronabinol (IHL-42X) at low, medium high doses on OSA severity endotypes. Methods Participants with (apnoea-hypopnoea index; AHI≥15events/hr) received 1-week IHL-42X each 3 placebo, separated by washout. The change from baseline AHI, oxygen desaturation index (ODI), Epworth sleepiness score (ESS), mood (profile states) final night treatment arm relative to placebo were major endpoints. Adverse events (AEs) monitored throughout. Exploratory analyses determined polysomnography values. Results Ten 11 participants (mean AHI 40.7events/hr) completed least one arm. All demonstrated reduction when compared (low, -19.7±27.1; medium, -17.5±23.3; high, -16.4±23.8 versus -2.8±21.0events/hr; p< 0.05). ODI3% (-15.2±24.8; -15.4±19.0 -8.3±13.2events/hr, respectively) significantly different (-2.8±21.0events/hr). did alter ESS mood. No serious AEs occurred. However, 31 mild-moderate possibly, probably related occurred during dosing (4 low dose) 4 placebo. Relative baseline, loop gain decreased 15, 21 20% (Cohen’s d ≥0.59) doses, respectively, collapsibility improved 12.5% (d=1.06) dose only. Conclusion One week nightly was well tolerated, safe associated reductions severity. act reduce decreasing upper airway collapsibility, particularly dose. Support (if any) Incannex Healthcare Ltd supported this study.