Trial of AD036 in Obstructive Sleep Apnea

Study Overview
=================
Brief Summary
-----------------
This is a randomized, double blind, placebo-controlled, repeat-dose, parallel arm, outpatient and inpatient phase 2 clinical study to examine the efficacy and safety of three dose levels of AD036 versus placebo in patients with obstructive sleep apnea.

Detailed Description
-----------------
This was a randomized, double-blind, placebo-controlled, repeat-dose, parallel arm, outpatient and inpatient, multicenter, dose-finding study of the combination of atomoxetine and oxybutynin in adults with OSA documented by polysomnography (PSG). Approximately 140 subjects were to be randomized 1:1:1:1 to receive 1 of 3 different fixed-dose combinations of oxybutynin and atomoxetine or matching placebo. For all subjects, the study consisted of: A screening and baseline period in which subjects' eligibility was determined An initial 2-night, at-home blinded baseline period in which all subjects received placebo A 3-night, run-in period in which subjects received: Low-dose combination for subjects randomized to one of the 3 study treatment arms Placebo for subjects randomized to the placebo treatment arm A 7-night treatment period in which subjects received the treatment to which they were randomized, i.e., 1 of the 3 different fixed-dose combinations of drugs, or placebo An end of study visit

Official Title
-----------------
Phase 2, Placebo-Controlled, Parallel Group Dose-Finding Study to Evaluate the Efficacy and Safety of Three Dose Levels of AD036 in Adults With Obstructive Sleep Apnea

Conditions
-----------------
Obstructive Sleep Apnea

Intervention / Treatment
-----------------
* Drug: AD036 Dose 1
* Drug: AD036 Dose 2
* Drug: AD036 Dose 3
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Male participants between 25 to 65 years of age or female participants between 25 to 70 years of age. Key Inclusion Criteria: AHI ≥ 20 based on screening polysomnography Epworth Sleepiness Scale (ESS) score ≥ 4 for participants not using CPAP Previous surgical treatment for OSA is allowed if ≥ 1 year prior to enrollment Key Exclusion Criteria: 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. Clinically significant neurological disorder, including epilepsy/convulsions. Positive screen for drugs of abuse or substance use disorder as defined in DSM-V within 24 months prior to Screening Visit. A significant illness or infection requiring medical treatment in the past 30 days. Women who are pregnant or nursing. 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. 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. 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. Use of another investigational agent within 90 days or 5 half-lives, whichever is longer, prior to dosing. ESS total score > 18. Central apnea index > 5/hour on baseline PSG. Periodic limb movement arousal index >15/hour on baseline PSG. Hepatic transaminases >3X the upper limit of normal (ULN), total bilirubin >2X ULN (unless confirmed Gilbert syndrome), serum creatinine >2X ULN. <6 hours typical sleep duration. Night- or shift-work sleep schedule. Employment as a commercial driver or operator of heavy or hazardous equipment.

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 2-Night at Home<br>An initial 2-night, at-home blinded baseline period in which all subjects received placebo | Drug: Placebo<br>* Placebo oral capsule administered before sleep<br>|
| Experimental: 3-Night Run In<br>AD036 Dose 1 (Low Dose: 25/5) or Placebo | Drug: AD036 Dose 1<br>* AD036 Dose 1 oral capsule administered before sleep<br>* Other names: 25/5;Drug: Placebo<br>* Placebo oral capsule administered before sleep<br>|
| Experimental: 7-Night<br>A 7-night treatment period in which subjects received the treatment to which they were randomized, i.e., 1 of the 3 different fixed-dose combinations of drugs, or placebo | Drug: AD036 Dose 1<br>* AD036 Dose 1 oral capsule administered before sleep<br>* Other names: 25/5;Drug: AD036 Dose 2<br>* AD036 Dose 2 oral capsule administered before sleep<br>* Other names: 75/1.5;Drug: AD036 Dose 3<br>* AD036 Dose 3 oral capsule administered before sleep<br>* Other names: 75/5;Drug: Placebo<br>* Placebo oral capsule administered before sleep<br>|
| No Intervention: End of Study<br>End of Study Visit | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnea Hypopnea Index (AHI) | Number of participants with ≥50% reduction in apnea hypopnea index (AHI). AHI is the average number of apneas and hypopneas a person experiences each hour during sleep, to register as an event an apnea or hypopnea must last at least 10 seconds or longer. To measure this, doctors divide the total number of apneic and hypopneic events by the total number of hours the person was asleep. | 10 days |