Crossover Trial of AD109 in Obstructive Sleep Apnea

Study Overview
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Brief Summary
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This is a randomized, 4-period, placebo-controlled, crossover, phase 2 clinical study to examine the efficacy and safety of AD109 versus its individual components or placebo in patients with obstructive sleep apnea.

Detailed Description
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The study is designed to examine the efficacy and safety of AD109 to treat obstructive sleep apnea. The study is a four-period single-dose randomized crossover design in which patients will undergo overnight polysomnographic (PSG) testing with dosing of one of the following 4 treatments: AD109, atomoxetine, R-oxybutynin or placebo. Participants will return 2 weeks after their final crossover PSG for an end of study (EOS) visit.

Official Title
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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 AD109 in Obstructive Sleep Apnea

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: AD109
* Drug: Atomoxetine
* Drug: R-oxybutynin
* Drug: Placebo
* Diagnostic Test: Digit System Substitution Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female, between 25 to 65 years of age, inclusive, at the Screening Visit. AHI 10 to <20, or AHI ≥20 if meets other PSG criteria Exclusion Criteria: History of narcolepsy. Clinically significant craniofacial malformation. Clinically significant cardiac disease (e.g., rhythm disturbances, coronary artery disease or cardiac failure) or hypertension requiring more than 2 medications for control. A medication for these purposes is defined by dosage form, such that a combination antihypertensive medication is considered 1 medication CPAP should not be used for at least 2 weeks prior to first study PSG 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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AD109<br>Oral capsule administered before sleep | Drug: AD109<br>* Oral administration before bed<br>Diagnostic Test: Digit System Substitution Test<br>* a neuropsychological test sensitive to brain damage, dementia, age and depression where numbers are assigned symbols. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured.<br>* Other names: DSST;|
| Active Comparator: Atomoxetine<br>Oral capsule administered before sleep | Drug: Atomoxetine<br>* Oral administration before bed<br>Diagnostic Test: Digit System Substitution Test<br>* a neuropsychological test sensitive to brain damage, dementia, age and depression where numbers are assigned symbols. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured.<br>* Other names: DSST;|
| Active Comparator: R-oxybutynin<br>Oral capsule administered before sleep | Drug: R-oxybutynin<br>* Oral administration before bed<br>Diagnostic Test: Digit System Substitution Test<br>* a neuropsychological test sensitive to brain damage, dementia, age and depression where numbers are assigned symbols. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured.<br>* Other names: DSST;|
| Placebo Comparator: Placebo<br>Oral capsule administered before sleep | Drug: Placebo<br>* Oral administration before bed<br>Diagnostic Test: Digit System Substitution Test<br>* a neuropsychological test sensitive to brain damage, dementia, age and depression where numbers are assigned symbols. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured.<br>* Other names: DSST;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hypoxic Burden (HB) Log10HB[(%*Min)/Hour] | Change in Hypoxic Burden (HB) is calculated as the oxygen desaturation 'area under the curve' in association with individual apneas and hypopneas. Due to the known logarithmic distribution of HB, data are primarily expressed and analyzed as Log10HB 4%[% min/hour]. Events with 4% or greater desaturations were included in the calculation of HB. | 1 night (treatment duration) (0-8 hours collected continuously) |