A randomised dose finding study of combination dronabinol and acetazolamide for the treatment of obstructive sleep apnoea.

Study Objectives: Current treatments for obstructive sleep apnoea (OSA) are ineffective or not tolerated in a proportion of patients. Other therapeutic options are needed and pharmaceuticals may provide an alternative. This randomised, double-blind, placebo-controlled, cross-over study examined the effect of combination acetazolamide and dronabinol (IHL-42X) at low, medium and high doses on OSA severity.

Methods: Participants with OSA (apnoea-hypopnoea index; AHI≥15events/hr) received 1-week of IHL-42X at each of 3 doses, and placebo, each separated by 1-week washout. The change from baseline in AHI, oxygen desaturation index (ODI), Epworth sleepiness score (ESS), and mood (profile of mood states) on the final night of each treatment arm relative to the change from baseline to placebo were the major endpoints. Adverse events (AEs) were monitored throughout.

Results: Ten of 11 participants completed the final night of at least one treatment arm. IHL-42X demonstrated a greater reduction in AHI from baseline compared with placebo (low, -19.7±27.1; medium, -17.5±23.3; high, -16.4±23.8 versus placebo, -2.8±21.0 events/hr; all p<0.05). The change from baseline in ODI3% was greater for the medium IHL-42X dose when compared with placebo (-15.4±19.0 versus placebo, -2.8±21.0 events/hr; p<0.05) but not the low or high doses (low, -15.2±24.8; high, -8.3±13.2 events/hr). IHL-42X did not change ESS or mood. No serious AEs occurred however 35 mild-moderate possibly, probably or treatment related AEs occurred during IHL-42X dosing and 5 occurred during placebo.

Conclusions: One week of nightly IHL-42X at low, medium, and high doses was well tolerated, safe and associated with significant reductions in OSA severity.