Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea
- Registration Number
- NCT05412004
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 469
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
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tirzepatide MTD_GPI1 Tirzepatide 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 Placebo_GPI1 Placebo Participants not on PAP therapy received placebo QW as an SC injection for 52 weeks. Tirzepatide MTD_GPI2 Tirzepatide 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 Placebo_GPI2 Placebo Participants who are on PAP therapy received placebo QW as an SC injection for 52 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in Apnea-Hypopnea Index (AHI) 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.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Apnea-Hypopnea Index (AHI) Baseline, Week 52 Percent Change From Baseline in AHI was evaluated.
Percentage of Participants With ≥50% AHI Reduction From Baseline Week 52 Percentage of participants achieving ≥50% AHI reduction from baseline to Week 52 was evaluated.
Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10 Week 52 The percentage of participants with OSA remission (AHI \<5 events per hour of sleep) or with mild OSA without excessive daytime sleepiness (AHI 5-14 events per hour of sleep with ESS ≤10) at Week 52 was evaluated. The ESS is used to assess improvements in excessive daytime sleepiness from baseline to Week 52. The ESS is an 8-item, participant-completed measure that asks the participant to rate, on a scale of 0 (no chance of dozing) to 3 (high chance of dozing), their usual chances of dozing in 8 different daytime situations, with a recall period of "in recent times." The ESS total score is the sum of the 8-item scores and ranges from 0 to 24, with higher scores indicating greater daytime sleepiness.
Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour) Baseline, Week 52 SASHB was determined by measuring the respiratory event-associated area under the curve for oxygen desaturation from pre-event baseline and represents the cumulative burden of intermittent hypoxia caused by OSA-related sleep-disordered breathing at sleep.
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 PROMIS SRI consists of 8 items that assess self-reported perceptions of alertness, sleepiness, and tiredness during usual waking hours and perceived functional impairments associated with sleep problems. PROMIS SRI has a recall period of "in the past 7 days" and each item is rated on a 5-point scale from "not at all" to "very much." PROMIS SD consists of 8 items that assess self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. PROMIS SD has a recall period of "in the past 7 days" and each item is rated on a 5-point scale ranging from "not at all" to "very much," "never" to "always," or "very poor" to "very good." For both PROMIS SRI and PROMIS SD, item responses are used to generate T-scores which are standardized scores with a mean of 50 and a standard deviation of 10 (score range cannot be specified for T-scores). Higher T-scores indicate worse outcomes; more sleep-related impairment (PROMIS SRI) or more sleep disturbance (PROMIS SD).
Percent Change From Baseline in Body Weight Baseline, Week 52 Percent Change from Baseline in Body Weight was evaluated.
Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration Baseline, Week 52 HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment.
Change From Baseline in Systolic Blood Pressure (SBP) Baseline, Week 48 Change in systolic blood pressure from baseline to Week 48 was evaluated.
Trial Locations
- Locations (57)
NeuroScience Research Center
🇺🇸Canton, Ohio, United States
BR Trials - Ensaios Clinicos e Consultoria
🇧🇷São Paulo, Brazil
InnoDiab Forschung Gmbh
🇩🇪Essen, Nordrhein-Westfalen, Germany
Hospital das Clinicas FMUSP
🇧🇷São Paulo, Brazil
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Rocky Mountain Clinical Research
🇺🇸Idaho Falls, Idaho, United States
CPCLIN
🇧🇷Sao Paulo, São Paulo, Brazil
CPQuali Pesquisa Clínica
🇧🇷São Paulo, Brazil
CTI-CRC
🇺🇸Cincinnati, Ohio, United States
NeuroTrials Research Inc
🇺🇸Atlanta, Georgia, United States
Sleep Therapy Research Center
🇺🇸San Antonio, Texas, United States
Lillestol Research
🇺🇸Fargo, North Dakota, United States
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Artemis Institute for Clinical Research
🇺🇸Riverside, California, United States
Teradan Clinical Trials, LLC
🇺🇸Brandon, Florida, United States
Palm Beach Research Center
🇺🇸West Palm Beach, Florida, United States
Brengle Family Medicine
🇺🇸Indianapolis, Indiana, United States
FutureSearch Trials of Neurology
🇺🇸Austin, Texas, United States
Preferred Primary Care Physicians
🇺🇸Uniontown, Pennsylvania, United States
Advanced Neuro Research Center - ANRC
🇺🇸El Paso, Texas, United States
Office 18
🇺🇸Pittsburgh, Pennsylvania, United States
Epic Medical Research
🇺🇸Red Oak, Texas, United States
Flinders University
🇦🇺Bedford Park, South Australia, Australia
Woolcock Institute of Medical Research
🇦🇺Sydney, New South Wales, Australia
Gadolin Research
🇺🇸Beaumont, Texas, United States
Núcleo de Pesquisa Clínica do Rio Grande do Sul
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Rainier Clinical Research Center
🇺🇸Renton, Washington, United States
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Wuxi People's Hospital
🇨🇳Wuxi, Jiangsu, China
The Second Affiliated Hospital of Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
West China Hospital, Sichuan University
🇨🇳ChengDu, Sichuan, China
Zhongshan Hospital,Fudan University
🇨🇳Shanghai, Shanghai, China
Siteworks GmbH
🇩🇪Hannover, Niedersachsen, Germany
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Praglandia s.r.o
🇨🇿Praha 5, Czechia
RESM Respiratory and Sleep Medical Care Clinic
🇯🇵Yokohama, Kanagawa, Japan
Institut für Diabetesforschung GmbH Münster
🇩🇪Münster, Nordrhein-Westfalen, Germany
Diabeteszentrum Hamburg West
🇩🇪Hamburg, Germany
RED-Institut GmbH
🇩🇪Oldenburg, Schleswig-Holstein, Germany
Kirigaokatsuda Hospital
🇯🇵Kitakyushu, Fukuoka, Japan
Koujunkai Daido Clinic
🇯🇵Nagoya, Aichi, Japan
Sakai City Medical Center
🇯🇵Sakai, Osaka, Japan
Lungenpraxis Schleswig
🇩🇪Schleswig, Schleswig-Holstein, Germany
Fukuwa Clinic
🇯🇵Chuo-ku, Tokyo, Japan
Advanced Sleep Research
🇩🇪Berlin, Germany
Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares
🇲🇽Mexico City, Distrito Federal, Mexico
Osaka Kaisei Hospital
🇯🇵Osaka, Japan
RM Pharma Specialists
🇲🇽Mexico City, Distrito Federal, Mexico
Unidad de Investigación Clínica y Atención Médica HEPA
🇲🇽Guadalajara, Jalisco, Mexico
Servicios Integrales Nova de Monterrey S.A. de C.V.
🇲🇽San Nicolas de los Garza, Nuevo León, Mexico
Private Practice - Dr. Arechavaleta Granell Maria del Rosario
🇲🇽Guadalajara, Jalisco, Mexico
Investigacion En Salud Y Metabolismo Sc
🇲🇽Chihuahua, Mexico
Unidad Médica para la Salud Integral
🇲🇽San Nicolás de los Garza, Nuevo León, Mexico
Puerto Rico Medical Research Center
🇵🇷Hato Rey, Puerto Rico
China Medical University Hospital
🇨🇳Taichung, Taiwan
Arké SMO S.A de C.V
🇲🇽Veracruz, Mexico