A Randomised Four-Period Cross-Over Phase I Study to Assess Bioavailability, Bioequivalence and Tolerability of IHL-42X Compared to the Reference Drugs in Healthy Volunteers

This is a 4-period crossover bioequivalence and bioavailability clinical trial designed to assess the pharmacokinetics and safety and tolerability of IHL-42X compared to the reference listed drugs Marinol (reference listed drug for dronabinol) and Taro acetazolamide (reference listed drug for acetazolamide). The study will look to enrol at least 116 participants. Participants will be enrolled into one of four treatment groups, each group consisting of approximately 29 participants, which will receive all four treatments in different orders, as defined by period 1, period 2, period 3 and period 4.

The trial will recruit healthy participants if they satisfy all the following criteria:

1. Ages ≥18 to ≤65 at the time of screening
2. BMI ≥18.0 to ≤32.0
3. Physically well, in the opinion of the investigator, with no clinically significant psychiatric, cardiac, hepatic, renal, endocrine, gastrointestinal, bleeding, thyroid, cholesterol, or hypertension disorders
4. If male, willing to use an approved method of contraception from 30 days prior to dosing, throughout the study, and 90 days after last dose.
5. If female of non-childbearing potential, must be postmenopausal with established serum FSH levels >30IU/L (determined during screening or have undergone one of the sterilization procedures, as noted in the protocol, at least 6 months prior to Visit Day 1 If females of childbearing potential, must not be currently pregnant, lactating, or planning to be pregnant and are willing to use an approved method of contraception, as noted in the protocol, from 30 days prior to dosing, throughout the study, and 30 days after last dose. Partner has had a vasectomy at least 6 months prior to first dose Of non-childbearing potential (postmenopausal or surgically sterile by any method for at least 3 months prior to check-in) Abstinence Same sex relationship
6. Voluntarily consent to participate in the study and complete all study required tasks, as instructed by the protocol, including the completion of questionnaires.

Participants will be excluded from participating in the study if there is evidence of any of the following at screening, or prior to dosing at the timepoints in the Schedule of Events:

1. History of cardiac disease or arrythmias
2. History of significant psychiatric illness (defined as hospitalisation or history of pharmacological prescription for psychiatric conditions), suicidal ideation, or suicidal attempts
3. Current use of illicit drugs or as defined by a positive urine drug test at screening or baseline
4. History of alcohol abuse or excessive alcohol intake according to the Australian guidelines (more than 10 standard drinks per week/4 standard drinks per day on average) or alcohol consumption (by self-declaration) defined as > 21 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit, or a 125 mL glass of wine).
5. Any cannabis use within 30 days of screening
6. Known hypersensitivity and/or intolerance to any cannabis products with previous use
7. Known hypersensitivity and/or intolerance to sesame oil (dronabinol is formulated in sesame oil)
8. Known hypersensitivity and/or intolerance to acetazolamide
9. Has taken any vitamins, herbal remedies, supplements or cannabidiol products within 7 days of each check-in
10. GAD-7 score of ≥15, MDI score ≥31 OR 3 core symptoms and 5 accompanying symptoms, C-SSRS score ≥4 OR reported suicidal behaviour within the past 3 months
11. Any dietary requirements incompatible with study breakfast; must be able to eat high- fat, high-calorie diet (including meat, dairy products) (As described in FDA guidance for BA and BE studies (See Appendix 6 in protocol))
12. Hepatic or renal impairment or disease, as defined as AST/ALT >1.5 x ULN, eGFR <60 at screening and check-in.
13. History of gastrointestinal disorders or previous surgeries which may impact absorption, distribution, metabolism and/or excretion of the IP (such as cholecystitis, cholecystectomy)
14. Female participants who are pregnant, lactating or planning to become pregnant
15. Inability to adhere to the protocol and study restrictions during the study period
16. Participation in another clinical trial of an investigational drug within 30 days or 5 half- lives of the investigational drug (whichever is longer) prior to first study drug administration.
17. Any other reason in the opinion of the investigator