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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 140
- 试验地点
- 12
- 主要终点
- Apnea Hypopnea Index (AHI)
研究概览
简要总结
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.
详细描述
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
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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:
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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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 >
- •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.
研究组 & 干预措施
2-Night at Home
An initial 2-night, at-home blinded baseline period in which all subjects received placebo
干预措施: Placebo (Drug)
3-Night Run In
AD036 Dose 1 (Low Dose: 25/5) or Placebo
干预措施: AD036 Dose 1 (Drug)
3-Night Run In
AD036 Dose 1 (Low Dose: 25/5) or Placebo
干预措施: Placebo (Drug)
7-Night
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
干预措施: AD036 Dose 1 (Drug)
7-Night
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
干预措施: AD036 Dose 2 (Drug)
7-Night
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
干预措施: AD036 Dose 3 (Drug)
7-Night
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
干预措施: Placebo (Drug)
结局指标
主要结局
Apnea Hypopnea Index (AHI)
时间窗: 10 days
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.
次要结局
未报告次要终点