Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect and safety of tirzepatide in participants with 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.

Official Title
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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

Conditions
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Sleep Apnea, Obesity

Intervention / Treatment
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* Drug: Tirzepatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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)

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirzepatide Maximum Tolerated Dose<br>Participants will receive a low dose and then increase to a maximum tolerated dose 1 or dose 2 subcutaneously (SC). GPI1: Participants are unwilling or unable to use PAP therapy. GPI2: Participants are on PAP therapy. | Drug: Tirzepatide<br>* Administered SC<br>* Other names: LY3298176;|
| Placebo Comparator: Placebo<br>Participants will receive placebo SC GPI1: Participants are unwilling or unable to use PAP therapy. GPI2: Participants are on PAP therapy. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Apnea-Hypopnea Index (AHI) |  | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A Hierarchical Combination of Functional Outcomes of Sleep Questionnaire (FOSQ) 10 Score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score | A hierarchical combination of change from baseline in the FOSQ 10 score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score will be assessed by the win ratio. The reported unit will be the total wins for each treatment group from performing a hierarchical comparison of the components. | Baseline (Week 0) to Study Completion (Estimated Up to 52 Weeks) | 
| 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 | 
| Percent Change from Baseline in Body Weight |  | Baseline, Week 52 | 
| Change from Baseline in Systolic Blood Pressure (SBP) |  | Baseline, Week 48 | 
| Change from Baseline in High Sensitivity C reactive Protein (hsCRP) Concentration |  | Baseline, Week 52 | 
| Change from Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% min/hour) |  | Baseline, Week 52 |