Incannex Healthcare Inc. (Nasdaq: IXHL) has announced positive topline results from a pharmacokinetics (PK) and safety study of IHL-42X, a novel, oral fixed-dose combination of acetazolamide and dronabinol for the treatment of Obstructive Sleep Apnea (OSA). The study, involving 125 healthy volunteers, demonstrated that IHL-42X achieved similar pharmacokinetic profiles and equivalent total drug exposure levels compared to the reference listed drugs (RLD) for dronabinol and acetazolamide. These findings support the potential for a future FDA 505(b)(2) new drug application (NDA).
Bioavailability and Pharmacokinetics
The study confirmed the bioavailability of IHL-42X, demonstrating the delivery of both dronabinol and acetazolamide. The pharmacokinetic profile of IHL-42X mirrored those observed for the respective RLDs, including equivalent total exposure levels for the drug molecules. Furthermore, the administration of IHL-42X with food did not substantially affect the overall exposure to acetazolamide, while an increase in overall exposure to THC was observed, consistent with the known properties of dronabinol.
Safety and Tolerability
The PK study also highlighted the safety and tolerability of IHL-42X. No serious adverse events were reported during the trial. Most Treatment-Emergent Adverse Events (TEAEs) were mild to moderate. The proportion of subjects reporting at least one TEAE during the IHL-42X fasted period (57.4%) was similar to the dronabinol fasted period (52.1%). Fewer subjects reported TEAEs during the acetazolamide fasted treatment period (37.8%). Food did not significantly affect the number of subjects reporting TEAEs for IHL-42X, with 57.4% fasted versus 58.8% fed.
Implications for Regulatory Pathway
According to Incannex's Chief Scientific Officer, Mark Bleackley, Ph.D., the topline IHL-42X PK findings provide data necessary to support a 505(b)(2) application in accordance with FDA guidance, assuming continued positive results from Phase 2 and 3 clinical trials. This pathway allows Incannex to leverage existing safety and toxicology data from the reference listed drugs, potentially streamlining the approval process.
Ongoing Clinical Development
IHL-42X is currently undergoing evaluation in the global Phase 2/3 RePOSA trial, which is assessing its efficacy and safety in individuals with OSA who are non-compliant, intolerant, or naïve to positive airway pressure devices, including CPAP. The Phase 2 portion of the trial is being conducted in the United States, with the expanded Phase 3 portion including sites in the United Kingdom and European Union. Topline results from the U.S. Phase 2 portion are anticipated in the first half of 2025.
About IHL-42X and Obstructive Sleep Apnea
IHL-42X is an oral fixed-dose combination of acetazolamide and dronabinol designed to act synergistically on two different physiological pathways associated with the intermittent hypoxia (IH) and hypercapnia that characterize OSA. A prior Australian Phase 2 clinical trial demonstrated that IHL-42X reduced the Apnea-Hypopnea Index (AHI) in all dosage strengths, with the lowest dose reducing AHI by an average of 51 percent relative to baseline.
Obstructive sleep apnea is a prevalent condition characterized by repetitive episodes of upper airway obstruction during sleep, leading to disrupted sleep and various health complications. Current treatments often involve devices like CPAP machines, which can be cumbersome and poorly tolerated by some patients. IHL-42X represents a potential new therapeutic option for individuals with OSA, particularly those who struggle with existing treatments.
