RePOSA-Revealing the Efficacy of IHL-42X Use in Patients with OSA

Inclusion Criteria:

1. Aged ≥18 years of age

2. Screening polysomnography (PSG) findings confirmed on central over-read:

3. AHI ≥15

4. ≤ 25% central or mixed apneas/hypopneas

5. no Cheyne-Stokes respiration

6. total sleep time ≥ 2 hours

7. Intolerant, non-compliant, or naïve to PAP (Note: No more than 25% of the studypopulation will consist of PAP-naïve patients). Patients will be identified asintolerant, non-compliant, or naïve to PAP devices by the following criteria:

8. Patients are regarded as PAP-non-compliant if they do not use PAP for ≥ 4 hoursfor at least 21 nights during consecutive 30-day period based on data collectedfrom the PAP device (eg, SD storage cards) and/or a cloud-based repository ofPAP device data.

9. Patients are regarded as PAP-intolerant if they are former PAP users, ie, a PAPdevice that they have not used for >30 days or who do not have access to PAPdevice

10. 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, arenot considered PAP- naïve and should be categorised according to a through babove. (Note: PAP-naïve patients will have the benefits and risks of PAPexplained at screening, including that PAP is standard of care for OSA. Thesepatients also have the option to withdraw from the study at any time if he/sheelects to be treated with PAP or other alternative therapy such as an oralappliance or surgery)

11. Must agree not to take any form of cannabis or cannabinoid, or any other illicit orrecreational drug with the exception of the investigational product (IP) whileparticipating in this study.

12. A female patient of childbearing potential must agree to use 2 approved methods ofcontraception. Approved methods of contraception include the following:

13. 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

14. Barrier method (condom or diaphragm) for at least 3 months prior to Day 1through to 10 days after the last dose of the study drug

15. Stable hormonal contraceptive which includes oral, intravaginal, intrauterine,transdermal, injectable, or implantable methods of hormonal contraception forat least 3 months prior to Day 1. A female will not be considered of childbearing potential if:

16. 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea withserum FSH levels > 40 mIU/ml

17. undergone bilateral tubal ligation, hysterectomy, or bilateral oophorectomy atleast 6 months prior to Day 1

18. A male patient must agree to use at least 1 approved method of contraception (or asrequired by local regulations) while engaging in sexual activity from study Day -1through End-of-Study (EOS) follow-up and/or up to 10 days following the lastadministration of the study drug. Male patients must not donate sperm during thissame period. Approved methods of contraception include the following:

19. Barrier method (condom) for at least 14 days prior to Day 1 through to 10 daysafter the final dose of the study drug

20. Surgical sterilisation (vasectomy) at least 6 months prior to Day 1

21. Voluntarily written consent to participate in the study and be willing and able toparticipate in all scheduled visits, treatment plans, tests, and other studyprocedures according to the protocol

Exclusion Criteria:

1. Body mass index >45 kg/m2

2. PAP-compliant, defined by the use of PAP for ≥ 4 hours for at least 21 nights duringthe consecutive 30-day period

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

4. Maxillomandibular advancement, upper airway, or bariatric surgery within the last 6months prior to first administration of the study drug; or patients who areconsidering surgical treatment

5. Use of benzodiazepines, sedative-hypnotics, or stimulants (ATC N06B, N05C, N05BA,N03AE, and N01AF categories) to treat insomnia, OSA, other sleep disorders

6. Pierre Robin, Treacher Collins, or other craniofacial malformation syndrome, orgrade ≥3 tonsillar hypertrophy

7. Chronic neuromuscular disorders such as motor neuron disease, muscular dystrophy, ormyopathy

8. Known allergic reaction to cannabis products with previous use

9. Known allergic reaction to sesame oil

10. Known allergic reaction to acetazolamide

11. Pregnant or breast-feeding

12. Current illicit drug abuse (within the last 6 months prior to screening) ; "abuse"has some subsets that are objective and some that require investigator judgement;questions should be discussed with the medical monitor or with the sponsor

13. An objective subset includes consumption of substances that are "illicit", i.e.not legal per local laws

14. Investigator judgement is expected for legally marketed products ingested forother than the approved indication(s)

15. Severe depression, defined as a score of ≥30 on the Major Depression Inventoryquestionnaire

16. Severe anxiety, defined as score of >15 on the General Anxiety Disorder-7questionnaire

17. Any of the following co-morbid conditions (Note: clarification on co-morbidities andinclusion/exclusion criteria may be discussed with the medical monitor and/orsponsor):

18. severe psychiatric disorder that might be aggravated or exacerbated bydronabinol's potential to cause anxiety/nervousness, depersonalization,hallucination, etc;

19. cardiac dysfunction and/or its treatment that might augment dronabinol'spotential to cause tachycardia or vasodilation;

20. marked hepatic dysfunction as defined by elevated ALT or AST >3 times the upperlimit of normal, that would reduce dronabinol metabolism; one retest persubject is permitted at the discretion of the investigator; the subject maycontinue in RePOSA if BOTH repeat transaminase levels are within the referencerange;

21. current or history of encephalopathy or cirrhosis Child-Pugh category B or C (see Appendix 7) since acetazolamide can increase blood ammonia levelsprecipitating a bout of hepatic encephalopathy;

22. marked renal dysfunction, including eGFR <60 mL/min/1.73m2, as determined usingthe National Kidney Foundation calculator

23. hypokalaemia (low blood potassium), hyponatremia (low blood sodium),hyperchloraemic acidosis, and/or adrenal insufficiency that might be aggravatedor exacerbated by acetazolamide's activity as a carbonic anhydrase inhibitor

24. Other ongoing condition(s) that the investigator considers may be clinicallysignificant with regards to the patient's safe participation in this study or mayconfound this study's findings; any consideration should be discussed with themedical monitor or with the sponsor

25. Participation in any other interventional studies involving investigational ormarketed products within 30 days or 5.5 half-lives, whichever is longer, of the IPprior to screening. Patients in Phase II may enter screening (with a differentidentifier) for Phase III after 30 days from the last administration of the studydrug in Phase II.