Open-Label 4-Period Dose-Escalation Safety and Efficacy Study of AD313 in Participants With Obstructive Sleep Apnea

Exclusion criteria

• Medical Conditions 1. History of clinically significant sleep disorder other than OSA. 2. Clinically significant craniofacial malformation. 3. Clinically significant cardiac disease (e.g., rhythm disturbances, coronary artery disease or cardiac failure) or hypertension requiring more than 2 medications for control (combination medications are considered as 1 medication for this purpose). 4. Clinically significant neurological disorder, including epilepsy/convulsions. 5. History of schizophrenia, schizoaffective disorder or bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders-5 (DSM 5) or International Classification of Disease tenth edition criteria. 6. History of attempted suicide within 1 year prior to screening, or current suicidal ideation. 7. Medically unexplained positive screen for drugs of abuse or history of substance use disorder as defined in DSM-V within 24 months prior to Screening Visit. 8. A significant illness or infection requiring medical treatment in the past 30 days. 9. Clinically significant cognitive dysfunction as determined by investigator. 10. Women who are pregnant or nursing. Prior/Concomitant Therapy 11. History of using devices for OSA treatment, including CPAP, oral or nasal devices, or positional devices, may enroll as long as the devices have not been used for at least 2 weeks prior to first study visit and are not used during participation in the study. 12. History of chronic oxygen therapy. 13. Use of medications from the list of disallowed concomitant medications. 14. Treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors, strong cytochrome P450 2D6 (CYP2D6) inhibitors, or monoamine oxidase inhibitors (MAOI) within 14 days of the start of treatment, or concomitant with treatment. Prior/Concurrent Clinical Study Experience 15. Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing. Diagnostic Assessments 16. Hepatic transaminases \>2X the upper limit of normal (ULN), total bilirubin \>1.5X ULN (unless confirmed Gilbert syndrome), estimated glomerular filtration rate \< 60 ml/min. 17. PLM arousal index \>15 Other Exclusions 18. \<5 hours typical sleep duration. 19. ESS \> 18 20. Night- or shift-work sleep schedule which causes the major sleep period to be during the day. 21. Employment as a commercial driver or operator of heavy or hazardous equipment. 22. Typically smoking more than 10 cigarettes or 2 cigars per day, or inability to abstain from smoking during overnight PSG visits. 23. Unwilling to use specified contraception. 24. History of regular alcohol consumption of more than 14 standard units per week (males) or more than 7 standard units per week (females), or unwillingness to limit alcohol consumption to no greater than 2 units/day (males), 1 unit per day (females), not to be consumed within 3 hours of bedtime or on PSG nights. 25. Unwilling to limit during the study period caffeinated beverage intake (e.g., coffee, cola, tea) to 400 mg/day or less of caffeine, not to be used within 3 hours of bedtime. 26. Any condition that in the investigator's opinion would present an unreasonable risk to the participant, or which would interfere with their participation in the study or confound study interpretation. 27. Participant considered by the investigator, for any reason, an unsuitable candidate to receive atomoxetine and/or dronabinol or unable or unlikely to understand or comply with the dosing schedule or study evaluations. Meals and Dietary Restrictions 1. Participants should refrain from consumption of any nutrients known to modulate CYP enzyme activity (e.g., grapefruit or grapefruit juice, pomelo juice, star fruit, pomegranate, and Seville or Moro \[blood\] orange products) within 72 hours before the first dose of study drug and during the study. 2. Diet should be generally stable during the study, e.g., new diet programs should not be initiated. Caffeine, Alcohol, and Tobacco 1. During the outpatient portions of the study, participants should refrain from more than 2 standard units per day of alcohol for men or 1 unit/day for women, consumed no less than 3 hours prior to bedtime. Alcohol should not be consumed on PSG nights. 2. Moderate consumption of caffeinated beverages, containing up to a total of 400 mg caffeine per day, is permitted during the study period, consumed no less than 3 hours prior to bedtime.