Phase II, Randomized, Double-Blind, Multidose Crossover Clinical Trial to Determine the Safety and Efficacy of IHL-42X in Subjects With Obstructive Sleep Apnea
The goal of this randomized, double-blind, multi-dose crossover clinical trial is to determine the safety and efficacy of IHL-42X in subjects with obstructive sleep apnea. The primary endpoint is: Change in AHI4 at the end of each treatment period compared to baseline (each treatment period is 28 days). The study will consist of three separate four-way crossover dose-comparison studies each comparing three dose strengths of IHL-42X to placebo. The double-blind four-way crossover will be conducted according to a Williams design. Each of the crossover studies will test different doses of dronabinol in combination with a distinct, set dose of acetazolamide. In total, nine different combinations of dronabinol and acetazolamide formulated as IHL-42X will be tested in the study. The optimal dose strength will be selected based on safety and efficacy over a 4-week treatment period.
∙ Participants must satisfy all the following criteria at screening unless otherwise stated:
• Aged ≥18 and ≤65 years of age at the time of consent.
• Two screening PSG findings confirmed on central over-read that both must meet the below criteria:
‣ AHI4 ≥5
⁃ ≤25% central or mixed apneas out of total AHI
⁃ no Cheyne-Stokes respiration
⁃ total sleep time ≥ 4 hours in each PSG
⁃ \< 30 periodic leg movement disorder arousals per hour.
• A difference in AHI4 of ≤15 between screening PSG 1 and screening PSG 2.
• A PROMIS-SRI 8a score of \>16.
• Intolerant or non-compliant to PAP, or has refused PAP after physician recommendation. Participants will be identified as intolerant or non-compliant to PAP devices by the following criteria (NB: OSA diagnosis must be entered in participant medical history):
‣ Participants are regarded as PAP-non-compliant if they do not use PAP for ≥ 4 hours for at least 63 nights during consecutive 90-day period based on data collected from the PAP device (e.g., SD storage cards) and/or a cloud-based repository of PAP device data.
⁃ Participants are regarded as PAP-intolerant if they are former PAP users, i.e., a PAP device that they have not used for \>90 days, have tried PAP and not continued to use it or refusal of PAP after prior positive sleep study or prior refusal of provider recommended sleep study due to unwillingness to consider PAP.
• NB: Participants will have the benefits and risks of PAP explained at screening, including that PAP is standard of care for OSA. Participants 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 with the exception of the IP, or any other illicit or recreational drug while participating in this study.
• A female participant of childbearing potential must agree to at least one approved highly effective method of contraception. Approved methods of contraception include the following:
‣ Intra-uterine device in place for at least 3 months prior to Day 1 through to 10 days following the last dose of the study drug.
⁃ Stable hormonal contraceptive which includes oral, intravaginal, intrauterine, transdermal, injectable, or implantable methods of hormonal contraception for at least 3 months prior to Day 1 through to 10 days after the last dose of the study drug.
‣ NB: Barrier method (condom or diaphragm) is not considered 'highly effective' for the purpose of this study and should be used in combination with one of the approved highly effective methods listed above.
‣ A female will not be considered of childbearing potential if:
⁃ 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels \> 40 mIU/ml.
⁃ Undergone bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months prior to Day 1.
• A male participant must agree to use at least 1 approved method of contraception (or as required by local regulations) while engaging in sexual activity from study Day -1 through EOS follow-up and/or up to 10 days following the last administration of the study drug. Male participants must not donate sperm during this same period. Approved methods of contraception include the following:
‣ Barrier method (condom) from date of consent through to 10 days after the final dose of the study drug.
⁃ Surgical sterilization (vasectomy) at least 6 months prior to Day 1 with proof of azoospermia.
• Voluntarily written consent to participate in the study and be willing and able to participate in all scheduled visits, treatment plans, tests, and other study procedures according to the protocol.