Summary:
Incannex Healthcare announced positive results from a pharmacokinetics (PK) and safety study of IHL-42X, a novel fixed-dose combination of dronabinol and acetazolamide for obstructive sleep apnea (OSA). The study confirmed the bioavailability of IHL-42X and established a safety profile similar to its reference listed drugs, supporting its potential FDA 505(b)(2) application. Ongoing phase 2/3 trials, including the RePOSA trial, aim to further evaluate IHL-42X for OSA patients who are non-compliant, intolerant, or naïve to positive airway pressure therapies.
Key Takeaways:
- Positive PK and Safety Results: The study confirmed the bioavailability of IHL-42X and found no serious adverse events, with a safety profile comparable to its reference listed drugs.
- FDA Pathway: The findings support a potential FDA 505(b)(2) application, leveraging existing safety and toxicology data from the reference drugs.
- Ongoing Clinical Trials: The global phase 2/3 RePOSA trial is underway, targeting OSA patients unable to tolerate positive airway pressure devices, with topline phase 2 results expected in 2025.
Incannex Healthcare Inc, a clinical-stage biopharmaceutical company, announced positive topline results from a completed 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 confirmed bioavailability of IHL-42X, demonstrating delivery of both dronabinol and acetazolamide. The PK profile of IHL-42X was similar to those observed for the respective reference listed drugs, including equivalent total exposure levels observed for the drug molecules.
Furthermore, administration of IHL-42X with food, in contrast to fasted conditions, indicated no substantial food effect on overall exposure to acetazolamide. Consistent with what is known for the reference listed drugs, an increase in overall exposure to THC was observed when IHL-42X was administered with food compared to fasted state.
No serious adverse events were reported during the study. All but one treatment-emergent adverse event (TEAE) was reported to be mild or moderate. The proportion of subjects reporting at least one TEAE on 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 have a substantial effect on the number of subjects reporting TEAEs for IHL-42X, with 57.4% fasted versus 58.8% fed.
Establishing FDA Pathway for IHL-42X
This data establishes a scientific bridge to the reference listed drugs, potentially enabling the company to leverage existing safety and toxicology data in a US Food and Drug Administration (FDA) 505(b)2 new drug application for IHL-42X and assist in the analysis of the global phase 2/3 RePOSA trial.
“The topline IHL-42X PK findings we are reporting today provide data necessary to support a 505(b)(2) application in accordance with FDA guidance, assuming continued positive results from our phase 2 and 3 clinical trials,” says Mark Bleackley, PhD, Incannex’s chief scientific officer, in a release. “The trial results are consistent with our expectations and the objectives for IHL-42X, a novel, oral fixed-dose combination therapeutic.”
The study was designed to assess the safety and pharmacokinetics of IHL-42X, a novel combination formulation, as compared to its respective FDA reference listed drugs. Conducted as a randomized, four-period crossover study in healthy volunteers at two sites in Australia, the trial involved 125 participants, 114 of whom completed all treatment periods.
Each treatment period involved the administration of one of four regimens: IHL-42X (dronabinol 5 mg, acetazolamide 250 mg) in fasted or fed state, dronabinol (5 mg) in a fasted state, or acetazolamide (250 mg) in a fasted state. Subjects were assigned to one of four sequences, with each sequence following a distinct order.
Promising Results from Prior Trials and Future Plans
In a prior Australian phase 2 clinical trial, IHL-42X was shown to reduce the apnea-hypopnea index (AHI) in all dosage strengths, with the lowest dose reducing AHI by an average of 51% relative to baseline. RePOSA, a global phase 2/3 clinical trial is underway, evaluating IHL-42X in individuals with OSA who are either non-compliant, intolerant, or naïve to positive airway pressure devices, including CPAP, with the phase 2 portion conducted in the United States.
The expanded phase 3 portion will include sites in the United Kingdom and the European Union. A topline readout from the US phase 2 portion is anticipated in the first half of 2025.
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