Phase 2 Randomized Double-Blind Placebo-Controlled Parallel-Arm Dose Finding Study to Compare Fixed Dose Combinations of AD109 and AD504 to Atomoxetine or Placebo in Obstructive Sleep Apnea
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 294
- 试验地点
- 25
- 主要终点
- Change in Apnea-Hypopnea Index (AHI4) From Baseline: Combined AD109 Arms vs. Placebo
研究概览
简要总结
This is a phase 2 randomized double-blind placebo-controlled parallel-arm dose finding study to compare fixed dose combinations of AD109 and AD504 to atomoxetine or placebo in Obstructive Sleep Apnea.
研究设计
- 研究类型
- 干预性
- 分配方式
- 随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 四盲 (受试者、医护人员、研究者、结局评估者)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- Between 18 to 65 years of age for men and 18-75 for women, inclusive, at the Screening Visit.
- Mean AHI 10 to 45 events/h, inclusive
- PGI-S: >1
- BMI between 18.5 and 38 kg/m2 for men and 40 kg/m2 for women, inclusive.
排除标准
- Current clinically significant sleep disorder other than OSA
- 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).
- Participants with a history of using devices for OSA treatment, including CPAP, oral or nasal devices, or positional devices, may enroll as long as the devices have not been used for at least 2 weeks prior to first PSG and are not used during participation in the study
研究组 & 干预措施
AD109 75/2.5mg
Atomoxetine 75 mg/Aroxybutynin 2.5 mg tablet
干预措施: AD109 (Drug)
AD504 75/100mg
Atomoxetine 75 mg tablet/Trazodone 100 mg capsule
干预措施: AD504 (Drug)
Placebo tablet
干预措施: Placebo (Drug)
Placebo tablet plus placebo capsule
干预措施: Placebo (Drug)
AD109 75/5mg
Atomoxetine 75 mg/Aroxybutynin 5 mg tablet
干预措施: AD109 (Drug)
Atomoxetine 75mg plus placebo
Atomoxetine 75 mg tablet/placebo capsule
干预措施: Atomoxetine Hydrochloride (Drug)
AD504 75/50mg
Atomoxetine 75 mg tablet/Trazodone 50 mg capsule
干预措施: AD504 (Drug)
Atomoxetine 75mg
Atomoxetine 75 mg tablet
干预措施: Atomoxetine Hydrochloride (Drug)
方案终点
主要结局
Change in Apnea-Hypopnea Index (AHI4) From Baseline: Combined AD109 Arms vs. Placebo
时间窗: Baseline (mean of PSG Visits 2 and 3) to Day 21 and Day 28 (PSG Visits 5 and 6)
Change in AHI4 (apnea-hypopnea index, 4% oxygen desaturation criterion; average respiratory events per hour of sleep) measured by in-lab polysomnography. Baseline was the mean of two pre-treatment PSG nights (Visits 2 and 3). Change from baseline was assessed at treatment PSG nights at approximately Day 21 (Visit 5) and Day 28 (Visit 6), modeled as repeated measures, with the reported value representing the model-based LS mean using equal (0.5/0.5) weighting between the Day 21 and Day 28 visits.
次要结局
- Change in Apnea-Hypopnea Index (AHI4) From Baseline: Combined AD504 Arms vs. Placebo(Baseline (mean of PSG Visits 2 and 3) to Day 21 and Day 28 (PSG Visits 5 and 6))
- Change in Apnea-Hypopnea Index (AHI4) From Baseline: Atomoxetine vs. Placebo(Baseline (mean of PSG Visits 2 and 3) to Day 21 and Day 28 (PSG Visits 5 and 6))
试验结果
结果已于 2026-08-12 在 ClinicalTrials.gov 公示。 在 ClinicalTrials.gov 查看
受试者流程
入组 294 人 · 完成 252 人
主要终点
Change in Apnea-Hypopnea Index (AHI4) From Baseline: Combined AD109 Arms vs. Placebo
events/hr · 95% Confidence Interval · 时间窗: Baseline (mean of PSG Visits 2 and 3) to Day 21 and Day 28 (PSG Visits 5 and 6)
| AD109 Combined Dose Arms （n=69） | AD109 75/5mg （n=35） | AD109 75/2.5mg （n=34） | Placebo （n=62） |
|---|---|---|---|
| -7.38 (-9.53–-5.23) | -7.40 (-10.41–-4.38) | -7.37 (-10.44–-4.30) | -0.21 (-2.49–2.07) |
mITT set: all randomized participants who received ≥1 dose and had ≥1 primary endpoint measurement. The two AD109 dose arms were combined as the primary analysis group per the pre-specified SAP (v1.0, April 2022), as the study was designed and powered to evaluate the overall effect of AD109 versus placebo rather than to compare individual dose levels. Results for the individual AD109 dose groups are presented descriptively to provide arm-level data.
Least Squares Mean Difference -7.17 · 95% 置信区间 -10.31–-4.04 · p = <0.0001 · Mixed Models Analysis
p-value is for two-sided test of the null hypothesis that the mean change from baseline is the same across the two treatments listing.
其他终点（2）
Change in Apnea-Hypopnea Index (AHI4) From Baseline: Combined AD504 Arms vs. Placebo
events/hr · 95% Confidence Interval · 时间窗: Baseline (mean of PSG Visits 2 and 3) to Day 21 and Day 28 (PSG Visits 5 and 6)
| AD504 Combined Dose Arms （n=76） | AD504 75/100mg （n=38） | AD504 75/50mg （n=38） | Placebo （n=62） |
|---|---|---|---|
| -8.02 (-9.98–-6.05) | -8.53 (-11.31–-5.74) | -7.50 (-10.29–-4.72) | -0.33 (-2.52–1.86) |
mITT set: all randomized participants who received ≥1 dose and had ≥1 primary endpoint measurement. The two AD504 dose arms were combined as the primary analysis group per the pre-specified SAP (v1.0, April 2022), as the study was designed and powered to evaluate the overall effect of AD504 versus placebo rather than to compare individual dose levels. Results for the individual AD504 dose groups are presented descriptively to provide arm-level data.
Least Squares Mean Difference -7.68 · 95% 置信区间 -10.63–-4.73 · p = <0.0001 · Mixed Models Analysis
Change in Apnea-Hypopnea Index (AHI4) From Baseline: Atomoxetine vs. Placebo
events/hr · 95% Confidence Interval · 时间窗: Baseline (mean of PSG Visits 2 and 3) to Day 21 and Day 28 (PSG Visits 5 and 6)
| Atomoxetine 75mg （n=50） | Placebo （n=62） |
|---|---|
| -5.40 (-7.93–-2.87) | -0.21 (-2.49–2.07) |
mITT set: all randomized participants who received ≥1 dose and had ≥1 primary endpoint measurement.
Least Squares Mean Difference -5.19 · 95% 置信区间 -8.59–-1.78 · p = 0.003 · Mixed Models Analysis
安全性
| 组别 | 严重不良事件 | 死亡 |
|---|---|---|
| AD109 75/5mg | 0 / 41 | 0 / 41 |
| AD109 75/2.5mg | 0 / 42 | 0 / 42 |
| AD504 75/100mg | 0 / 43 | 0 / 43 |
| AD504 75/50mg | 0 / 40 | 0 / 40 |
| Atomoxetine 75mg | 0 / 63 | 0 / 63 |
| Placebo | 0 / 63 | 0 / 63 |
数值为申办方在 ClinicalTrials.gov 公示的原始数据，未经重新计算；括号内为公示的离散度（如 95% 置信区间）。
相关文献
- 相关文献（PubMed 关联）Schweitzer PK, Taranto-Montemurro L, Ojile JM, Thein SG, Drake CL, Rosenberg R, Corser B, Abaluck B, Sangal RB, Maynard J. The Combination of Aroxybutynin and Atomoxetine in the Treatment of Obstructive Sleep Apnea (MARIPOSA): A Randomized Controlled Trial. Am J Respir Crit Care Med. 2023 Dec 15;208(12):1316-1327. doi: 10.1164/rccm.202306-1036OC. PubMed 37812772
研究者
研究点 (25)
标识符
- NCT 编号
- NCT05071612
- 其他研究编号
- MARIPOSA
日期
- 首次提交
- (5年前)
- 首次发布
- (4年前)
- 主要完成日期
- (4年前)
- 研究完成日期
- (4年前)
- 最近核实
- (2个月前)
- 最近更新
- (上个月)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 是否有结果
- 是