Proof of concept study on the combined effect of dronabinol and acetazolamide on apnoea hypopnoea index (AHI) in adults with obstructive sleep apnoea

INTERVENTION: This study will determine the therapeutic benefit of a combination of dronabinol and acetazolamide at reducing AHI in adults with obstructive sleep apnoea. Investigational product will be administered by mouth as two separate gel capsules. The first dose will be administered at the study site on the afternoon of day one of the treatment period. For the next six nights the dose will be administered approximately 60 min before bedtime each night. There are a total of seven doses, one per day, over a seven day treatment period. The study will consist of four treatment periods. Three doses, low (2.5 mg dronabinol 125 mg acetazolamide) medium (5 mg dronabinol 250 mg acetazolamide) and high (10 mg dronabinol 500 mg acetazolamide) and a placebo will be compared in this study to identify the dose with the best therapeutic benefit and least side effects. This is a cross‐over trial where all patients will receive all of the treatments. Each treatment will be administered for one seven‐day treatment period. Treatment periods will be separated by seven‐day washout periods. The study will consist of four treatment periods and four washout periods for 56 days total. Participants will be provided with a blister pack containing the investigational product at the start of each treatment period. Each blister will contain a single dose, one dronabinol and one acetazolamide gel capsule (or matched placebo), of the investigational product. Treatment adherence will be monitored through a self‐reporting treatment administration log and return of blister packs to the study team at the end of each treatment period. CONDITION: Obstructive Sleep Apnoea; ; Obstructive Sleep Apnoea Respiratory ‐ Sleep apnoea PRIMARY OUTCOME: Change in apnoea hyponea index (AHI) compared to baseline as assessed by overnight, in‐clinic polysomnography.[Night seven of the treatment period] SECONDARY OUTCOME: Change in alterness measured using the Stanford Sleepiness Scale[Night seven of the treatment period] Change in daytime somnolence measured by Epworth Sleepiness Scale[Night seven of the treatment period] Change in mood measured by the Profile of Mood States (POMS) questionnaire[Night seven of the treatment period] Change in oxygen desaturation index (ODI) assessed by overnight, in‐clinic polysomnography.[Night seven of the treatment period] Change in quality of life measured by Short‐form 36 questionnaire[Night seven of the treatment period] Plasma levels of COOHTHC the morning after dosing measured by LC‐MS.[The morning after night seven of the treatment period] Plasma levels of OHTHC the morning after dosing measured by LC‐MS[The morning after night seven of the treatment period] Plasma levels of THC the morning after dosing measured by LC‐MS[The morning after night seven of the treatment period] Seizure frequency in patients with comorbid epilepsy and sleep apnoea measured by self‐report seizure diary[Total over each seven day treatment period] INCLUSION CRITERIA: Aged between 21 and 65 years ‐ Evidence of OSA based on AHI greater than or equal to 15. The first PSG study will be analysed within 2 business days to confirm AHI criteria. ‐ No known allergic reaction to cannabis products with previous use (self‐disclosure). ‐ No known allergic reaction to sesame oil (dronabinol is formulated in sesame oil) ‐ No know allergic reaction to acetazolamide or other sulphonamides. ‐ Have no history of past substance abuse or current abuse of illicit drugs ‐ Physically well, in the opinion of the investigator, with no severe psychiatric, cardiac, renal, endocrine, gastrointestinal, or bleeding disorders ‐ If male, agree to be sexually abstinent or agree to use two approved methods of contraception when engaging in sexual activity from study Visit 1 through to the end of the study. Subjects must agree to use two approved methods of contraception for 10 days following the last administration of the study dru