A Phase II/III, Randomised, Double-Blind Clinical Trial 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
Overview
- Phase
- Phase 2
- Intervention
- IHL-42X Low Dose
- Conditions
- Obstructive Sleep Apnea
- Sponsor
- Incannex Healthcare Ltd
- Enrollment
- 560
- Locations
- 20
- Primary Endpoint
- Change in apnea-hypopnea index (AHI)
- Status
- Active, Not Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged ≥18 years of age
- •Screening polysomnography (PSG) findings confirmed on central over-read:
- •≤ 25% central or mixed apneas/hypopneas
- •no Cheyne-Stokes respiration
- •total sleep time ≥ 2 hours
- •Intolerant, non-compliant, or naïve to PAP (Note: No more than 25% of the study population will consist of PAP-naïve patients). Patients will be identified as intolerant, non-compliant, or naïve to PAP devices by the following criteria:
- •Patients are regarded as PAP-non-compliant if they do not use PAP for ≥ 4 hours for at least 21 nights during consecutive 30-day period based on data collected from the PAP device (eg, SD storage cards) and/or a cloud-based repository of PAP device data.
- •Patients are regarded as PAP-intolerant if they are former PAP users, ie, a PAP device that they have not used for \>30 days or who do not have access to PAP device
- •Patients are regarded as PAP-naïve if they have no prior experience with PAP. Patients who have undergone a split-study, ie, a study of PAP during PSG, are not considered PAP- naïve and should be categorised according to a through b above. (Note: PAP-naïve patients will have the benefits and risks of PAP explained at screening, including that PAP is standard of care for OSA. These patients also have the option to withdraw from the study at any time if he/she elects to be treated with PAP or other alternative therapy such as an oral appliance or surgery)
- •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.
Exclusion Criteria
- •Body mass index \>45 kg/m2
- •PAP-compliant, defined by the use of PAP for ≥ 4 hours for at least 21 nights during the consecutive 30-day period
- •Current use of oral appliances (eg, mandibular advancement device, tongue retaining device, or mouth guard)
- •Maxillomandibular advancement, upper airway, or bariatric surgery within the last 6 months prior to first administration of the study drug; or patients who are considering surgical treatment
- •Use of benzodiazepines, sedative-hypnotics, or stimulants (ATC N06B, N05C, N05BA, N03AE, and N01AF categories) to treat insomnia, OSA, other sleep disorders
- •Pierre Robin, Treacher Collins, or other craniofacial malformation syndrome, or grade ≥3 tonsillar hypertrophy
- •Chronic neuromuscular disorders such as motor neuron disease, muscular dystrophy, or myopathy
- •Known allergic reaction to cannabis products with previous use
- •Known allergic reaction to sesame oil
- •Known allergic reaction to acetazolamide
Arms & Interventions
Phase 2 Investigational Product - IHL-42X Low dose
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.
Intervention: IHL-42X Low Dose
Phase 2 Investigational Product - IHL-42X High dose
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.
Intervention: IHL-42X High Dose
Phase 2 Placebo
One capsule self-administered once daily every night approximately 1 hour prior to bed for 4 weeks.
Intervention: Placebo
Phase 3 Investigational Product - IHL-42X
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.
Intervention: IHL-42X (Optimal Dose)
Phase 3 Comparator - Reference Listed Drug/Dronabinol
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.
Intervention: Dronabinol
Phase 3 Comparator - Reference Listed Drug/Acetazolamide
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.
Intervention: Acetazolamide
Phase 3 Placebo
One capsule self-administered once daily every night approximately 1 hour prior to bed for 52 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Change in apnea-hypopnea index (AHI)
Time Frame: 52 weeks
Phase 3 - Assess the change in AHI compared to baseline