Human Trial Finds THC-Based Sleep Apnea Drug Well Tolerated With No Serious Adverse Events
- The Phase I trial of IHL-42X, a THC-based drug combining dronabinol and acetazolamide, was generally well tolerated with no serious adverse events among 125 healthy adult participants.
- The randomized crossover study in Australia assessed the drug’s bioavailability, pharmacokinetics, and tolerability under fed and fasted conditions, with most adverse events being mild to moderate.
- The most common side effects included sleepiness, headache, euphoric mood, and dizziness, with no unique adverse effects observed from the combination compared to individual drugs.
- Researchers confirmed oral delivery of both active components and noted food increased THC exposure; future studies will investigate repeated dosing in obstructive sleep apnea patients to assess efficacy and safety.
A THC-based drug being developed to treat obstructive sleep apnea was generally well tolerated in a Phase I human trial, with researchers reporting no serious adverse events among 125 participants.
The study, published September 12 in Clinical Drug Investigation, examined IHL-42X, an oral drug combining 5 milligrams of dronabinol, a synthetic form of delta-9 THC, with 250 milligrams of acetazolamide.
Researchers enrolled 125 healthy adults in Australia in a randomized four-period crossover trial designed to examine the drug’s bioavailability, pharmacokinetics and tolerability. Participants received IHL-42X while fasting and after eating, along with separate doses of dronabinol and acetazolamide for comparison.
Overall, researchers said IHL-42X was well tolerated under both fed and fasted conditions, with no serious adverse events reported during the study. Most treatment-emergent adverse events were mild or moderate.
At least one treatment-emergent adverse event was reported by 57.4% of participants receiving IHL-42X while fasting and 58.8% when the combination was taken after food. That compared with 52.1% for dronabinol alone and 37.8% for acetazolamide alone.
The most commonly reported effects associated with IHL-42X included sleepiness, headache, euphoric mood and dizziness. Researchers found no adverse effects unique to the combination that were not also observed with the individual reference drugs.
Of the 125 people enrolled, 114, or 91.2%, completed all four treatment periods.
The researchers also confirmed that the formulation successfully delivered both THC and acetazolamide orally. Food increased overall exposure to THC, an effect the researchers said will need to be considered as the drug advances through further clinical testing.
IHL-42X is being developed as a potential pharmaceutical treatment for obstructive sleep apnea, a condition in which breathing repeatedly stops or becomes restricted during sleep.
Previous clinical research involving people with obstructive sleep apnea found that nightly treatment with combinations of dronabinol and acetazolamide was associated with reductions in measures of sleep apnea severity. The newly published Phase I trial was not designed to determine whether IHL-42X improves sleep apnea, instead focusing on how the formulation is absorbed and tolerated.
“Single dose IHL-42X administered orally was, overall, well tolerated” in both fed and fasted participants, the researchers concluded.
They said future studies involving repeated doses in patients with obstructive sleep apnea will provide additional information about cumulative exposure and the drug’s risk-benefit profile.