A Master Protocol to Investigate the Efficacy and Safety of Tirzepatide Once Weekly in Participants Who Have Obstructive Sleep Apnea and Obesity: A Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 469
- 试验地点
- 57
- 主要终点
- Change From Baseline in Apnea-Hypopnea Index (AHI)
研究概览
简要总结
The purpose of this study is to evaluate the effect and safety of tirzepatide in participants with moderate to severe obstructive sleep apnea and obesity who are both unwilling or unable to use Positive Airway Pressure (PAP) therapy in GPI1 and those who are and plan to stay on PAP therapy in GPI2.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For GPI1 Participants:
- •Participants who are unable or unwilling to use PAP therapy. Participants must not have used PAP for at least 4 weeks prior to screening.
- •For GPI2 Participants:
- •Have been on PAP therapy for at least 3 consecutive months prior to screening and plan to continue PAP therapy during the study
- •For Both GPI1 and GPI2 Participants:
- •Have an AHI ≥15 on PSG as part of the trial at screening
- •Have a body mass index (BMI) ≥30 kilogram/square meter (kg/m²)
- •Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight
排除标准
- •For GPI2 Participants:
- •Have personal or job-related responsibilities, or in the opinion of the investigator have any situation, that would make it unsafe to stop PAP therapy for 7 days prior to PSG testing during the course of the study
- •Are unwilling to stop PAP therapy for 7 days prior to polysomnography (PSG) testing during the course of the study
- •For GPI1 and GPI2 Participants:
- •Female participants must not be pregnant, intending to be pregnant, breastfeeding, or intending to breastfeed.
- •Have type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), history of ketoacidosis, or hyperosmolar state/coma.
- •Have HbA1c ≥ 6.5% (≥ 48 mmol/mol) at baseline
- •Any previous or planned surgery for sleep apnea or major ear, nose or throat surgery, including tonsillectomy and adenoidectomy that still may affect breathing at time of baseline
- •Have significant craniofacial abnormalities that may affect breathing at baseline
- •Have diagnosis of Central or Mixed Sleep Apnea with % of mixed or central apneas/hypopneas ≥50%, or diagnosis of Cheyne Stokes Respiration
- •Diagnosis of Obesity Hypoventilation Syndrome or daytime hypercapnia.
- •Active device treatment of OSA other than PAP therapy (for example, dental appliance), or other treatment, that in the opinion of the investigator, may interfere with study outcomes, unless willing to stop treatment at baseline and throughout the study.
- •Respiratory and neuromuscular diseases that could interfere with the results of the trial in the opinion of the investigator.
- •Have a self-reported change in body weight >5 kg within 3 months prior to screening
- •Have a prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty if performed more than 1 year prior to screening)
- •Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months (for example, mucosal ablation, gastric artery embolization, intragastric balloon, and duodenal-jejunal bypass sleeve)
研究组 & 干预措施
Tirzepatide MTD_GPI1
Participants not on positive airway pressure (PAP) therapy received a maximum tolerated dose (MTD) of 10 milligrams (mg) or 15 mg of Tirzepatide once weekly (QW) as a subcutaneous (SC) injection for 52 weeks, including the initial dose escalation by 2.5 mg every 4 weeks
干预措施: Tirzepatide (Drug)
Placebo_GPI1
Participants not on PAP therapy received placebo QW as an SC injection for 52 weeks.
干预措施: Placebo (Drug)
Tirzepatide MTD_GPI2
Participants who are on PAP therapy received an MTD of 10 mg or 15 mg of Tirzepatide QW as an SC injection for 52 weeks, including the initial dose escalation by 2.5 mg every 4 weeks
干预措施: Tirzepatide (Drug)
Placebo_GPI2
Participants who are on PAP therapy received placebo QW as an SC injection for 52 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Apnea-Hypopnea Index (AHI)
时间窗: Baseline, Week 52
AHI, Apnea-Hypopnea Index, is the number of apneas or hypopneas recorded via polysomnography during the study per hour of sleep. Apnea is defined as a cessation of airflow lasting at least 10 seconds, hypopnea as a decrease in airflow by at least 30% from baseline for at least 10 seconds occurring with a drop in oxygen saturation (SpO₂) by at least 4%. AHI values are categorized as 5-15 events/hr = mild; 15-\<30 events/hr = moderate; and ≥ 30 events/hr = severe. a significant reduction in values indicates a positive outcome.
次要结局
- Percent Change From Baseline in Apnea-Hypopnea Index (AHI)(Baseline, Week 52)
- Percentage of Participants With ≥50% AHI Reduction From Baseline(Week 52)
- Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10(Week 52)
- Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour)(Baseline, Week 52)
- Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD)(Baseline, Week 52)
- Percent Change From Baseline in Body Weight(Baseline, Week 52)
- Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration(Baseline, Week 52)
- Change From Baseline in Systolic Blood Pressure (SBP)(Baseline, Week 48)