None listed
Conditions
Brief summary
The aims of this study are to determine the effects of the medication reboxetine and combination therapy (AD128) on OSA severity (as measured by the apnoea/hypopnoea index during overnight polysomnography) versus placebo. We will also examine other key sleep parameters and the effects on next day sleepiness and alertness.
Interventions
Randomised, placebo-controlled, 3-arm, cross-over study (~1 week wash-out between visits):
Arm 1: single dose of reboxetine (4mg) (oral capsule) immediately prior to sleep (single overnight, in-laboratory study)
Arm 2: single dose of combination therapy with AD128 (4mg for agent #1 and +5mg for agent #2) (oral capsule) immediately prior to sleep (single overnight, in-laboratory study)
Arm 3: placebo (oral capsule) immediately prior to sleep (single overnight, in-laboratory study)
Interventions
Randomised, placebo-controlled, 3-arm, cross-over study (~1 week wash-out between visits): Arm 1: single dose of reboxetine (4mg) (oral capsule) immediately prior to sleep (single overnight, in-laboratory study) Arm 2: single dose of combination therapy with AD128 (4mg for agent #1 and +5mg for agent #2) (oral capsule) immediately prior to sleep (single overnight, in-laboratory study) Arm 3: placebo (oral capsule) immediately prior to sleep (single overnight, in-laboratory study) Interventions will be administered by a study investigator on each visit just prior to sleep for these acute sleep studies to ensure adherence.
Sponsors
Flinders University
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Otherwise healthy men and women with obstructive sleep apnoea aged 18-65 years BMI between 18.5 and 40.0 kg/m2, inclusive, at visit 1.
Exclusion criteria
-Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study. Medical Conditions 1. History of narcolepsy. 2. Clinically significant craniofacial malformation. 3. Clinically significant cardiac disease (e.g., rhythm disturbances, coronary artery disease or cardiac failure) or poorly controlled hypertension. 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-V (DSM V) or International Classification of Disease tenth edition criteria. 6. History of attempted suicide or suicidal ideation within 1 year prior to screening, or current suicidal ideation. 7. History of clinically significant constipation, gastric retention, or urinary retention, benign prostatic hyperplasia. 8. History of moderate or severe hepatic or renal impairment. 9. History of drug abuse or substance use disorder as defined in DSM-V within 12 months. 10. A significant acute illness or infection requiring medical treatment in the past 30 days. 11. Clinically significant cognitive dysfunction. 12. Narrow angle glaucoma. 13. Women who are pregnant or nursing. 14. Allergy to the study medications 15. Any medication known to influence breathing, sleep/arousal or muscle physiology. 16. Claustrophobia. 17. Use of medications from the list of disallowed concomitant medications. 18. 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 study. Prior/Concurrent Clinical Study Experience 19. Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing. Other Exclusions 20. <5 hours typical sleep duration. 21. Night- or shift-work sleep schedule. 22. Employment as a commercial driver or operator of heavy or hazardous equipment. 23. Smoking more than 10 cigarettes or 2 cigars per day. 24. Unwilling to use contraception during the study (if relevant). 25. Unwilling to avoid alcohol on the days of the study. 26. Unwilling to limit 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 on study days. 27. 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. 28. Participant considered by the investigator, for any reason, an unsuitable candidate to receive the study medications or unable or unlikely to understand or comply with the study design.
Outcome results
None listed