AD109 Dose Finding in Mild to Moderate OSA

Study Overview
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Brief Summary
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This is a randomized, 3-period, placebo-controlled, crossover, phase 2 clinical study to examine the efficacy and safety of 2 doses of AD109 vs placebo in patients with mild obstructive sleep apnea.

Detailed Description
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Participants underwent initial pre-screening to determine potential study eligibility. Participants selected for further screening had either a previous history of OSA of a severity consistent with enrollment criteria or were at high risk (e.g. as assessed by STOP-Bang Questionnaire score). Only participants who met all non polysomnography (PSG) enrollment criteria at Visit 1 were eligible for a screening PSG.

Official Title
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Phase 2 Randomized Double-Blind Placebo-Controlled 3-Period Single-Dose Crossover Study to Evaluate the Safety and Efficacy of Two Doses of AD-109 in Mild to Moderate Obstructive Sleep Apnea

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: AD109 dose1- A
* Drug: AD109 dose2- B
* Drug: Placebo- C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AHI between 5 and 20 events/h PGI-S equal to or higher than 1, or one or more of the following symptoms: Snoring or nightime gasping/choking Daytime sleepiness, fatigue or decreased concentration Nonrefreshing sleep, sleep fragmentation (including from nocturia), or morning headache Irritability, decreased mood or libido Exclusion Criteria: History of narcolepsy. Clinically significant craniofacial malformation. Clinically significant cardiac disease (e.g. rhythm disturbances, coronary artery disease or heart failure or hypertension requiring more than 2 medications for control). CPAP should not be used for at least 2 weeks prior to the study 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 |
| --- | --- |
| Other: Sequence ABC<br>AD109 Dose 1- 75 mg (A), then AD109 Dose 2- 37.5 mg (B), then Placebo (C). | Drug: AD109 dose1- A<br>* Oral administration at bedtime<br>* Other names: AD109 75;Drug: AD109 dose2- B<br>* Oral administration at bedtime<br>* Other names: AD109 37.5;Drug: Placebo- C<br>* Oral administration at bedtime<br>|
| Other: Sequence ACB<br>AD109 Dose 1- 75 mg (A), then Placebo (C) then AD109 Dose 2- 37.5 mg (B) | Drug: AD109 dose1- A<br>* Oral administration at bedtime<br>* Other names: AD109 75;Drug: AD109 dose2- B<br>* Oral administration at bedtime<br>* Other names: AD109 37.5;Drug: Placebo- C<br>* Oral administration at bedtime<br>|
| Other: Sequence BAC<br>AD109 Dose 2- 37.5 mg (B), then AD109 Dose 1- 75 mg (A), then Placebo (C) | Drug: AD109 dose1- A<br>* Oral administration at bedtime<br>* Other names: AD109 75;Drug: AD109 dose2- B<br>* Oral administration at bedtime<br>* Other names: AD109 37.5;Drug: Placebo- C<br>* Oral administration at bedtime<br>|
| Other: Sequence BCA<br>AD109 Dose 2- 37.5 mg (B), then Placebo (C), then AD109 Dose 1- 75 mg (A) | Drug: AD109 dose1- A<br>* Oral administration at bedtime<br>* Other names: AD109 75;Drug: AD109 dose2- B<br>* Oral administration at bedtime<br>* Other names: AD109 37.5;Drug: Placebo- C<br>* Oral administration at bedtime<br>|
| Other: Sequence CAB<br>Placebo (C), then AD109 Dose 1- 75 mg (A), then AD109 Dose 2- 37.5 mg (B) | Drug: AD109 dose1- A<br>* Oral administration at bedtime<br>* Other names: AD109 75;Drug: AD109 dose2- B<br>* Oral administration at bedtime<br>* Other names: AD109 37.5;Drug: Placebo- C<br>* Oral administration at bedtime<br>|
| Other: Sequence CBA<br>Placebo (C), then AD109 Dose 2- 37.5 mg (B), then AD109 Dose 1- 75 mg (A) | Drug: AD109 dose1- A<br>* Oral administration at bedtime<br>* Other names: AD109 75;Drug: AD109 dose2- B<br>* Oral administration at bedtime<br>* Other names: AD109 37.5;Drug: Placebo- C<br>* Oral administration at bedtime<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hypoxic Burden (HB) Log Transformed - Log10HB[(%*Min)/h] | 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/h]. Raw measurement of HB (%min/h) is defined as the sum of individual areas (%min) divided by total sleep time (h). Events with 4% or greater desaturations were included in the calculation of HB. | 1 night (8 hours) | 
| Change in Hypoxic Burden (HB) Raw Values - HB[(%*Min)/h] | Change in Hypoxic Burden (HB) is calculated as the oxygen desaturation 'area under the curve' in association with individual apneas and hypopneas. Raw measurement of HB (%min/h) is defined as the sum of individual areas (%min) divided by total sleep time (h). Events with 4% or greater desaturations were included in the calculation of HB. | 1 night (8 hours) |