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Phase II

Phase 2 Randomized Double-Blind Placebo-Controlled 4-Period Single-Dose Crossover Factorial Study to Evaluate the Contribution of the Individual Drug Components to the Efficacy of the Combination of Atomoxetine and R-oxybutynin in Obstructive Sleep Apnea

  • Study HIC#:2000029180
  • Last Updated:07/15/2021

The study’s goal is to determine whether combination of R-oxybutinin and atomoxetine or each drug alone is effective for OSA.  Oxybutinin and atomoxetine are medications that have been long used to treat other medical conditions, but may be  potential treatments for OSA.  The study is a randomized, double-blinded, cross-over clinical trial. The study involves surveys, administration of study drugs or placebo on the nights of diagnostic polysomnography (a sleep study) and a clinical laboratory test (blood draw). The participants will undergo 4 to 5 in-laboratory polysomnography tests. This study is voluntary, and volunteers may refuse participation or withdraw at any time.

At the end of the study, participants are eligible to participate in a 4-week open-label extension study (a different study), where they will receive the 2-drug combination therapy for the duration of the study.

Ages 25 years to 65 years

Gender  Both

End Date: RECRUITMENT ENDS 26 MARCH 2021

  • Age25 years - 65 years
  • GenderBoth
  • Start Date02/08/2021
  • End Date04/29/2021

Eligibility Criteria

Eligibility Criteria

Please note, below inclusion/exclusion criteria are extensive and medically detailed. They may be difficult to interpret without study staff guidance. Please contact study staff if interested in the study or with any questions about inclusion/exclusion criteria to assess your candidacy for participation.

 

Inclusion Criteria:

Age and Sex

1. Males or females between 25 to 65 years of age

Objective Disease Measures

2. Apnea hypopnea index (AHI) of 10 to < 45, or AHI ≥ 45 if any one of the following criteria are met:

a. Fraction of hypopneas is >90% or

b. Mean oxygen desaturation of obstructive events is ≤4% or

c. Fraction of hypopneas is 50-90% and mean oxygen desaturation is 4-8%

Note: Hypopneas defined by 4% oxygen desaturation

Weight

3. Body mass index (BMI) between 18.5 and 40.0 kg/m2, inclusive, at the pre-PSG visit.

 Male participants:

4. If male and sexually active with female partner(s) of childbearing potential, participant must agree, from Study Day 1 through 1 week after the last dose of study drug, to practice the protocol specified contraception

 Female participants:

5. If a woman of childbearing potential (WOCBP), the participant must agree, from Study Day 1 through 1 week after the last dose of study drug, to practice the protocol specified Contraception. All WOCBP must have negative result of a serum pregnancy test performed at screening.

6. If female and of non-childbearing potential, the participant must be either postmenopausal (defined as age ≥ 55 years with no menses for 12 or more months without an alternative medical cause) or permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

Informed Consent

7. Participant voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB)-approved informed consent prior to performing any of the Screening Visit procedures.

8. Participant must be able to understand the nature of the study and must have the opportunity to have any questions answered.

 

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

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 hypertension requiring more than 2 medications for control (combination medications count as 1 medication).

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 or suicidal ideation within 1 year prior to screening, or current suicidal ideation.

7. History of clinically significant constipation, gastric retention, urinary retention or insomnia.

8. Medically unexplained positive screen for drugs of abuse (excluding THC/marijuana) or history of substance use disorder as defined in DSM-V within 24 months prior to Screening Visit.

9. A significant illness or infection requiring medical treatment in the past 30 days as determined by investigator.

10. Clinically significant cognitive dysfunction as determined by investigator.

11. Untreated narrow angle glaucoma.

12. Women who are pregnant or nursing.

 Prior/Concomitant Therapy

13. CPAP should not be used for at least 2 weeks prior to first study PSG and throughout the study.

14. History of using oral or nasal devices for the treatment of OSA may enroll as long as the devices are not used during participation in the study.

15. History of using devices to affect participant sleeping position for the treatment of OSA, e.g. to discourage supine sleeping position, may enroll as long as the devices are not used during participation in the study.

16. History of oxygen therapy.

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 treatment, or concomitant with treatment.

 Prior/Concurrent Clinical Study Experience

19. Use of another investigational agent within 30 days or 5 half-lives, whichever is longer, prior to dosing.

 Diagnostic Assessments

20. Epworth sleepiness score (ESS) total score > 18.

21. 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.

Other Exclusions

22. <5 hours typical sleep duration.

23. Night- or shift-work sleep schedule which causes the major sleep period to be during the day.

24. Employment as a commercial driver or operator of heavy or hazardous equipment.

25. Smoking more than 10 cigarettes or 2 cigars per day, or inability to abstain from smoking during overnight PSG visits.

26. Unwilling to use specified contraception.

27. Unwilling to limit during the study period alcohol consumption to no greater than 2 standard units/day for men or 1 units/day for women, not to be consumed within 3 hours of bedtime.

28. 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.

29. 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.

30. Participant considered by the investigator, for any reason, an unsuitable candidate to receive AD109 or unable or unlikely to understand or comply with the dosing schedule or study evaluations.

Sub-Investigator

For more information about this study, contact:

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