IHL-42X for Obstructive Sleep Apnea

(REPOSA Trial)

Recruiting at 19 trial locations

Overseen By Mira Baron

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Incannex Healthcare Ltd

Must not be taking: Sedative-hypnotics, Stimulants

Disqualifiers: Obesity, Sedative use, Severe depression, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

560 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IHL-42X, a combination of Dronabinol and Acetazolamide, to help people with obstructive sleep apnea who struggle with CPAP machines. The study consists of two phases: the first phase compares two doses of IHL-42X to a placebo to determine the best dose, while the second phase tests this optimal dose against its individual components and a placebo over a longer period. Suitable candidates for this trial have obstructive sleep apnea and either cannot tolerate, do not regularly use, or have not tried CPAP machines. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you do not take any form of cannabis or cannabinoid, or any other illicit or recreational drug while participating. Additionally, you cannot use sedative-hypnotics or stimulants to treat sleep disorders. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that IHL-42X, a combination of dronabinol and acetazolamide, is safe and well-tolerated for individuals with obstructive sleep apnea. In earlier studies, participants took various doses of IHL-42X for a week. These studies found no major safety concerns and demonstrated that the treatment reduced sleep apnea symptoms.

The lowest dose of IHL-42X proved particularly effective, reducing the apnea-hypopnea index (a measure of sleep apnea severity) by an average of 51% without causing serious side effects. This suggests that both low and high doses are generally safe for short-term use.

Longer trials are now testing the treatment to confirm its safety over an extended period. Since it is in the later stages of clinical trials, earlier studies have already provided some evidence supporting its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for obstructive sleep apnea focus on mechanical solutions like CPAP machines, which keep airways open during sleep. But IHL-42X offers a different approach by combining two active ingredients: dronabinol and acetazolamide. Dronabinol is a synthetic cannabinoid that may help regulate breathing patterns, while acetazolamide acts as a respiratory stimulant, potentially enhancing breathing efficiency. Researchers are excited about IHL-42X because it targets the condition at a biochemical level, offering a potential alternative for those who struggle with or can't tolerate traditional mechanical treatments.

What evidence suggests that this trial's treatments could be effective for obstructive sleep apnea?

Research shows that IHL-42X, a mix of dronabinol and acetazolamide, may help reduce the severity of obstructive sleep apnea (OSA). In this trial, participants may receive either low or high doses of IHL-42X, which studies have shown to significantly reduce OSA severity compared to a placebo over 28 days. This treatment improves the body's control of breathing in response to changes in oxygen levels, enhancing overall sleep quality. Additionally, the combination of dronabinol and acetazolamide effectively reduced the total time patients experienced low oxygen levels during sleep. These findings suggest that IHL-42X could be a helpful option for those dealing with OSA. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with moderate obstructive sleep apnea who either can't or won't use positive airway pressure (PAP) therapy. Participants should not have a significant portion of central or mixed apneas, no Cheyne-Stokes respiration, and must not use cannabis or similar drugs outside the study. They need to agree to contraception during and shortly after the trial.

Inclusion Criteria

Are you currently using a CPAP machine?

Are you looking for an alternative to a CPAP machine?

Have you ever used a CPAP machine?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase II Treatment

4-week dose-finding study comparing two dose strengths of IHL-42X to placebo

4 weeks

Weekly visits (in-person)

Phase III Treatment

Optimal dose strength of IHL-42X compared to component active ingredients and placebo

52 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• IHL-42X

Trial Overview The RePOSA trial tests IHL-42X at different doses against placebo in two phases: Phase II finds the best dose over 4 weeks; Phase III compares this optimal dose to its components—dronabinol and acetazolamide—and placebo over a year.

How Is the Trial Designed?

Group I: Phase 3 Investigational Product - IHL-42X Experimental Treatment 1 Intervention

IHL-42X (dose will be identified based on the safety and efficacy results in Phase II), one capsule self-administered once daily every night approximately 1 hour prior to bed for 52 weeks.

Group II: Phase 2 Investigational Product - IHL-42X Low dose Experimental Treatment 1 Intervention

IHL-42X (2.5 mg dronabinol + 125 mg acetazolamide), one capsule self-administered once daily every night approximately 1 hour prior to bed for 4 weeks.

Group III: Phase 2 Investigational Product - IHL-42X High dose Experimental Treatment 1 Intervention

IHL-42X (5 mg dronabinol + 250 mg acetazolamide), one capsule self-administered once daily every night approximately 1 hour prior to bed for 4 weeks.

Group IV: Phase 3 Comparator - Reference Listed Drug/Dronabinol Active Control 1 Intervention

One capsule of dronabinol (equivalent dose strength to that in the IHL-42X optimal dose strength) self-administered once daily every night approximately 1 hour prior to bed for 3 months then IHL-42X (optimal dose) one capsule self-administered once daily every night approximately 1 hour prior to bed for the remaining 9 months.

Group V: Phase 3 Comparator - Reference Listed Drug/Acetazolamide Active Control 1 Intervention

One capsule of acetazolamide (equivalent dose strength to that in the IHL-42X optimal dose strength) self-administered once daily every night approximately 1 hour prior to bed for 3 months then IHL-42X (optimal dose) one capsule self-administered once daily every night approximately 1 hour prior to bed for the remaining 9 months.

Group VI: Phase 3 Placebo Placebo Group 1 Intervention

One capsule self-administered once daily every night approximately 1 hour prior to bed for 52 weeks.

Group VII: Phase 2 Placebo Placebo Group 1 Intervention

One capsule self-administered once daily every night approximately 1 hour prior to bed for 4 weeks.

Who Is Running the Clinical Trial?

Incannex Healthcare Ltd

Lead Sponsor

Trials

3

Recruited

710+

Published Research Related to This Trial

Acetazolamide (AZT) significantly improved sleep apnea symptoms in patients with high loop gain sleep apnea (HLGSA) both acutely and over a 3-month period, showing a notable reduction in the apnea hypopnea index (AHI) and breathing-related arousal index when combined with positive airway pressure (PAP) therapy.

The study involved 231 participants, with a strong predictor for treatment response being the non-rapid eye movement (NREM) AHI, indicating that AZT is a well-tolerated and effective option for managing HLGSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea. Ni, YN., Holzer, RC., Thomas, RJ.[2023]

Dronabinol treatment in 15 patients with obstructive sleep apnea (OSA) significantly increased theta power in the EEG, suggesting potential benefits for sleep quality.

The study found that higher doses of dronabinol were associated with enhanced ultradian rhythms in the EEG, which may correlate with improved sleepiness and reduced apnea-hypopnea index (AHI) scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of dronabinol on quantitative electroencephalogram (qEEG) measures of sleep in obstructive sleep apnea syndrome. Farabi, SS., Prasad, B., Quinn, L., et al.[2021]

In a Phase II trial involving 73 adults with moderate to severe obstructive sleep apnea (OSA), dronabinol significantly reduced the apnea-hypopnea index (AHI) by up to 12.9 events/hour compared to placebo, indicating its potential efficacy as a treatment.

Participants taking 10 mg of dronabinol reported greater satisfaction with their treatment and experienced a significant reduction in daytime sleepiness, as measured by the Epworth Sleepiness Scale, suggesting that dronabinol may improve both sleep quality and overall well-being in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea. Carley, DW., Prasad, B., Reid, KJ., et al.[2019]

Among older adults, those with chronic obstructive pulmonary disease (COPD) were more likely to use synthetic oral cannabinoids (0.6%) compared to those without COPD (0.3%), indicating a higher prevalence of off-label use in this population.

Older adults with COPD not only used synthetic cannabinoids more frequently but also for longer durations and at higher doses, raising potential safety concerns that warrant further research on the respiratory effects of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription Synthetic Oral Cannabinoid use Among Older Adults with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study. Vozoris, NT., Yao, Z., Li, P., et al.[2020]

Acetazolamide significantly improves sleep apnea at high altitudes by reducing the Apnea-Hypopnea Index (AHI) and increasing nocturnal oxygenation, particularly in healthy trekkers compared to those with obstructive sleep apnea (OSA).

A daily dose of 250 mg of acetazolamide may be as effective as higher doses for healthy individuals, suggesting a potential optimal therapeutic dose for treating sleep apnea in high-altitude conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis. Liu, HM., Chiang, IJ., Kuo, KN., et al.[2018]

In a proof-of-concept study involving 17 adults with Obstructive Sleep Apnea (OSA), dronabinol (Δ(9)THC) was found to be safe and well-tolerated at doses ranging from 2.5 to 10 mg daily.

Dronabinol significantly reduced the Apnea Hypopnea Index (AHI) by an average of 14.1 events per hour after 21 days of treatment, indicating its potential efficacy in managing OSA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proof of concept trial of dronabinol in obstructive sleep apnea. Prasad, B., Radulovacki, MG., Carley, DW.[2021]

In a study involving 45 patients with obstructive sleep apnea (OSA), acetazolamide significantly improved oxygen levels and reduced breathing disturbances at high altitudes compared to a placebo, indicating its potential as an alternative treatment when CPAP is not used.

Acetazolamide not only enhanced nocturnal oxygen saturation and reduced apnea/hypopnea indices but also improved sleep quality and prevented high blood pressure during altitude exposure, suggesting it stimulates ventilation effectively in OSA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with obstructive sleep apnea syndrome benefit from acetazolamide during an altitude sojourn: a randomized, placebo-controlled, double-blind trial. Nussbaumer-Ochsner, Y., Latshang, TD., Ulrich, S., et al.[2017]

In a study of 86 healthy lowlanders aged 40 and older, ascending to 3100 m caused significant hypoxemia and increased sleep apnea, with notable declines in oxygen saturation and sleep quality.

Preventive treatment with acetazolamide improved oxygen levels and reduced breathing disturbances during sleep at high altitude, but it did not significantly affect overall sleep duration or structure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of altitude and acetazolamide on sleep and nocturnal breathing in healthy lowlanders 40 y of age or older. Data from a randomized trial. Graf, LC., Furian, M., Bitos, K., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11985395/

A randomized dose finding study of combination dronabinol ... The effect of each dose of IHL-42X on additional outcomes relating to changes in OSA severity (cumulative event duration, time spent with SaO2 <90%, respiratory ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06146101

RePOSA-Revealing the Efficacy of IHL-42X Use in Patients ... The goal of this randomised, double-blind phase II/III clinical trial is to determine the safety and efficacy of IHL-42X in subjects with obstructive sleep ...

3. healio.com healio.com/news/pulmonology/20250813/topline-results-dronabinol-acetazolamide-combination-lowers-osa-severity-over-28-days

Dronabinol, acetazolamide combination lowers OSA severity Two different doses of an oral combination pharmacotherapy for obstructive sleep apnea significantly lowered disease severity vs. placebo at ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1389945725002114

The impact of acetazolamide and dronabinol on ... Our findings suggest that medium and high doses of Aceta-Dro primarily reduce OSA severity by lowering loop gain, while the efficacy of the low dose was due to ...

5. neurologylive.com neurologylive.com/view/ihl-42x-enter-phase-3-trials-obstructive-sleep-apnea-following-positive-phase-2-data

IHL-42X to Enter Phase 3 Trials for Obstructive Sleep ... Incannex's IHL-42X shows promising results in treating obstructive sleep apnea, demonstrating significant improvements in key metrics and a ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39589391/

A randomized dose finding study of combination ... One week of nightly IHL-42X at low, medium, and high doses was well tolerated, safe, and associated with significant reductions in OSA ...

7. incannex.com incannex.com/pipeline/ihl-42x-obstructive-sleep-apnea/

Incannex's IHL-42X | Obstructive Sleep Apnea In this trial, the lowest dose of IHL-42X was observed to be the most effective, reducing AHI by an average of 51 percent relative to baseline, where 25 percent ...

8. academic.oup.com academic.oup.com/sleep/article/48/4/zsae276/7908945

randomized dose finding study of combination dronabinol and ... This randomized, double-blind, placebo-controlled, crossover study examined the effect of a combination of acetazolamide and dronabinol (IHL-42X) at low, ...