Abstract
STUDY OBJECTIVES: Current treatments for obstructive sleep apnea (OSA) are ineffective or not tolerated in a proportion of patients. Other therapeutic options are needed and pharmaceuticals may provide an alternative. This randomized, double-blind, placebo-controlled, crossover study examined the effect of a combination of acetazolamide and dronabinol (IHL-42X) at low, medium, and high doses on OSA severity. METHODS: Participants with OSA (apnea-hypopnea index; AHI ≥15 events/hour) received 1 week of IHL-42X at each of three doses and placebo, each separated by a 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 vs. placebo, -2.8 ± 21.0 events/hour; all p < .05). The change from baseline in ODI3% was greater for the medium IHL-42X dose when compared with placebo (-15.4 ± 19.0 vs. placebo, -2.8 ± 21.0 events/hour; p < .05) but not the low or high doses (low, -15.2 ± 24.8; high, -8.3 ± 13.2 events/hour). 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.