A Randomized Four-Period Cross-Over Phase I Study to Assess Bioavailability, Bioequivalence, and Tolerability of IHL-42X Compared with the Reference Drugs in Healthy Volunteers.
George Williams Mbogo, Amanda Sallama, Parisa Asvadi et al.
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In 30 seconds
This phase I, randomized four-period crossover study assessed bioavailability, bioequivalence, food effects, and tolerability of IHL-42X—a combination of dronabinol and acetazolamide—in healthy volunteers at two Australian sites. IHL-42X was generally well tolerated, with no serious adverse events. Against reference acetazolamide, bioequivalence was met for AUC0-inf (0.910 [90% CI 0.865, 0.958]) and AUC0-last (0.882 [90% CI 0.838, 0.929]), but not Cmax (0.597 [90% CI 0.550, 0.647]). For THC, bioequivalence was met for AUC0-inf but not Cmax or AUC0-last. Food increased overall THC exposure.
Key findings
- No serious adverse events occurred; most treatment-emergent adverse events were mild or moderate.
- For acetazolamide, bioequivalence was met for AUC0-inf (0.910 [90% CI 0.865, 0.958]) and AUC0-last (0.882 [90% CI 0.838, 0.929]), but not Cmax.
- For THC, bioequivalence was met for AUC0-inf (0.948 [90% CI 0.822, 1.093]), but not Cmax or AUC0-last.
- The authors report increased overall THC exposure with food.
Why it matters
A fixed combination intended to deliver dronabinol and acetazolamide needs pharmacokinetic and tolerability characterization before its clinical effects can be assessed. These results support oral delivery of both components, while the failure to meet bioequivalence criteria for some exposure measures indicates that the combination does not match all reference-drug pharmacokinetic parameters. The study does not establish efficacy for obstructive sleep apnea.
What to keep in mind
This phase I study involved healthy volunteers and assessed pharmacokinetics and tolerability, not clinical efficacy or outcomes in people with obstructive sleep apnea.