The drug candidate demonstrated statistically significant reductions in AHI and improvements in oxygenation, coupled with positive patient-reported outcomes.
Key takeaways:
- IHL-42X met its primary endpoint, producing statistically significant reductions in AHI versus placebo, with some patients showing reductions of up to 83%.
- Both low and high doses improved oxygen desaturation index (ODI), wake after sleep onset, and supine AHI, while preserving REM sleep.
- Patient-reported outcomes highlighted improved sleep quality, reduced daytime sleepiness, better cognitive function, and greater ease with daily tasks.
- No serious adverse events were reported; side effects were infrequent and mild to moderate in severity.
- Results support progression to phase 3 trials following FDA end-of-phase 2 discussions.
Incannex Healthcare Inc announced positive topline results and patient-reported outcomes from its RePOSA Phase 2 clinical trial of IHL-42X, an oral drug candidate for treating obstructive sleep apnea (OSA). The study showed that the fixed-dose combination of dronabinol and acetazolamide achieved statistically significant improvements in key clinical endpoints and was well tolerated by participants.
The randomized, double-blind, placebo-controlled study enrolled 121 adults with moderate to severe OSA. Participants received a high dose, low dose, or placebo version of IHL-42X for a 28-day treatment period. The results are now being used to prepare for an end-of-phase 2 meeting with the US Food and Drug Administration (FDA) to plan for phase 3 development.
“Our recent phase 2 results for IHL-42X exceeded expectations,” says Joel Latham, president and CEO of Incannex, in a release. “In some patients, we observed reductions in AHI of up to 83%, which is an extraordinary outcome and a powerful signal of the drug’s potential.”
Clinical Efficacy Data
The trial met its primary endpoint, demonstrating a statistically significant reduction in the apnea-hypopnea index (AHI) from baseline for both low- and high-dose IHL-42X groups compared to placebo (p<0.05). Maximum AHI reductions reached up to 83% for the high-dose group.
According to the company, 41.2% of patients in the high-dose group and 33.3% in the low-dose group achieved a greater than 30% reduction in AHI. Reductions exceeding 50% were seen in 14.7% of high-dose patients and 13.9% of low-dose patients.
Other key findings from the trial include:
- Oxygen Desaturation Index (ODI): Both dose groups showed statistically significant improvements in ODI.
- Polysomnography Metrics: The high-dose arm demonstrated a 29.8% reduction in wake after sleep onset and a 30.3% decrease in AHI during supine sleep.
- REM Sleep: IHL-42X did not reduce the proportion of time spent in REM sleep, a side effect of some other drugs used for sleep indications.
“These findings highlight the statistically significant treatment effects observed across multiple measures of disease severity and patient experience,” says Mark Bleackley, PhD, chief scientific officer of Incannex, in a release. “Combined with an excellent safety and tolerability profile, the results provide strong validation of IHL-42X’s potential as an innovative and impactful therapy for obstructive sleep apnea.”
Patient-Reported Outcomes
In structured exit interviews conducted before unblinding, participants reported that wanting access to a CPAP alternative, as well as desires for improved health and better sleep, as motivators for joining the trial. The interviews, aligned with FDA guidance on Patient-Focused Drug Development, also provided qualitative assessments of patient experience.
Key findings from the exit interviews include:
- 57.6% of participants reported a perceived improvement in their OSA,
- 89.5% of those reporting improvement described the change as meaningful to their lives, and
- Reported benefits included: improved sleep quality, feeling more refreshed in the morning, reduced daytime sleepiness and fatigue, fewer cognitive disturbances, and greater ease in completing daily responsibilities.
Clinically significant improvements were noted in several patient-reported outcome measures, including the Functional Outcomes of Sleep Questionnaire-10, PROMIS Sleep-Related Impairment 8a, PROMIS Fatigue 7a, and the Epworth Sleepiness Scale. The low-dose group also showed statistically significant improvements in the Patient Global Impression of Change score.
“We believe the findings from the patient exit interviews underscore that these improvements are not just clinical—they are translating into meaningful, positive changes in patients’ daily lives,” Latham says.
Safety
IHL-42X was well tolerated in the trial. No serious adverse events were reported during the treatment period, and treatment-emergent adverse effects were infrequent and primarily mild or moderate in severity.
