IHL-42X for Obstructive Sleep Apnea

(REPOSA Trial)

Recruiting at 24 trial locations

Overseen By Stacey Layle

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

Trial Summary

What is the purpose of this trial?

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 apnoea who are intolerant, non-compliant, or naïve to positive airway pressure. Phase II study will be a 4-week dose-finding study comparing two dose strengths of IHL-42X to placebo. The optimal dose strength will be selected based on comparing the safety and efficacy of the two IHL-42X dose strengths to placebo over a 4-week treatment period. The three treatment groups are; IHL-42X Low dose (2.5mg dronabinol, 125mg acetazolamide), IHL-42X High dose (5mg dronabinol, 250mg acetazolamide) and Placebo. Each treatment group will enrol approximately 40 patients per treatment arm, for a total of approximately 120 patients. The safety and efficacy results of the Phase II study will be used to select the dose strength of IHL-42X and corresponding doses of dronabinol and acetazolamide in Phase III. Phase III study will use the optimal dose strength of IHL-42X identified in Phase II and will be compared to the component active pharmaceutical ingredients at equivalent dose strengths to those found in the IHL-42X optimal dose strength and placebo over 52 weeks. The four treatment groups are; IHL-42X (optimal dose from Phase II), Acetazolamide (equivalent dose strength to that in the IHL-42X optimal dose strength), Dronabinol (equivalent dose strength to that in the IHL-42X optimal dose strength) and placebo. The treatment groups will enrol approximately 165 patients in IHL-42X, approximately 55 patients in dronabinol, approximately 55 in acetazolamide, and approximately 165 in placebo, for a total of approximately 440 patients.

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.

What data supports the effectiveness of the drug IHL-42X for treating obstructive sleep apnea?

Research shows that dronabinol, a component of IHL-42X, has shown promise in treating obstructive sleep apnea by stabilizing sleep patterns and reducing breathing issues during sleep. Additionally, acetazolamide, another component, has been effective in treating sleep apnea, especially at high altitudes. ^{1 2 3 4 5}

Is IHL-42X safe for humans?

Dronabinol, a component of IHL-42X, has been studied for safety in people with obstructive sleep apnea and chronic obstructive pulmonary disease, showing some promise but also potential adverse respiratory effects. Acetazolamide, another component, has been used to prevent sleep disturbances at high altitudes and in certain types of sleep apnea, indicating it is generally safe for these uses. ^{2 3 4 6 7}

How is the drug IHL-42X different from other treatments for obstructive sleep apnea?

IHL-42X is unique because it combines dronabinol, which helps stabilize breathing during sleep, with acetazolamide, which can improve breathing disturbances, especially at high altitudes. This combination targets different aspects of sleep apnea, potentially offering a novel approach compared to standard treatments like CPAP (continuous positive airway pressure). ^{1 3 4 6 8}

Eligibility Criteria

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

Must agree not to take any form of cannabis or cannabinoid, or any other illicit or recreational drug with the exception of the investigational product (IP) while participating in this study

Screening polysomnography (PSG) findings confirmed on central over-read: AHI ≥15, ≤ 25% central or mixed apneas/hypopneas, no Cheyne-Stokes respiration

Intolerant, non-compliant, or naïve to PAP (No more than 25% of the study population will consist of PAP-naïve patients)

Exclusion Criteria

Known allergic reaction to cannabis products with previous use

Current illicit drug abuse (within the last 6 months prior to screening)

Current use of oral appliances (eg, mandibular advancement device, tongue retaining device, or mouth guard)

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The effect of acetazolamide on sleep apnea at high altitude: a systematic review and meta-analysis. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial: Effects of Dronabinol in Obstructive Sleep Apnea. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Proof of concept trial of dronabinol in obstructive sleep apnea. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Acute and long-term effects of acetazolamide in presumed high loop gain sleep apnea. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Impact of dronabinol on quantitative electroencephalogram (qEEG) measures of sleep in obstructive sleep apnea syndrome. [2021]

6. United States 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. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Prescription Synthetic Oral Cannabinoid use Among Older Adults with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study. [2020]

8. United States 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. [2017]