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

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 469
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2037
      • Woolcock Institute of Medical Research
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders University
• Brazil
  • São Paulo, Brazil, 01228-000
    • CPQuali Pesquisa Clínica
  • São Paulo, Brazil, 05003-090
    • BR Trials - Ensaios Clinicos e Consultoria
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas FMUSP
  • São Paulo, Brazil, 04266-010
    • Hospital das Clinicas FMUSP
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90430-001
      • Núcleo de Pesquisa Clínica do Rio Grande do Sul
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 01228-200
      • CPCLIN
• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University
    • Wuxi, Jiangsu, China, 214023
      • Wuxi People's Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital,Fudan University
  • Sichuan
    • ChengDu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
• Czechia
  • Praha 2, Czechia, 12808
    • Vseobecna fakultni nemocnice v Praze
  • Praha 5, Czechia, 150 00
    • Praglandia s.r.o
• Germany
  • Berlin, Germany, 10117
    • Advanced Sleep Research
  • Hamburg, Germany, 22607
    • Diabeteszentrum Hamburg West
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30449
      • Siteworks GmbH
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45136
      • InnoDiab Forschung GmbH
    • Münster, Nordrhein-Westfalen, Germany, 48145
      • Institut für Diabetesforschung GmbH Münster
  • Schleswig-Holstein
    • Oldenburg, Schleswig-Holstein, Germany, 23758
      • RED-Institut GmbH
    • Schleswig, Schleswig-Holstein, Germany, 24837
      • Lungenpraxis Schleswig
• Japan
  • Osaka, Japan, 532-0003
    • Osaka Kaisei Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 457-8511
      • Koujunkai Daido Clinic
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 802-0052
      • Kirigaokatsuda Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 222-0033
      • RESM Respiratory and Sleep Medical Care Clinic
  • Osaka
    • Sakai, Osaka, Japan, 593-8304
      • Sakai City Medical Center
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0031
      • Fukuwa Clinic
• Mexico
  • Chihuahua, Mexico, 31217
    • Investigacion En Salud Y Metabolismo Sc
  • Veracruz, Mexico, 91910
    • Arké SMO S.A de C.V
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 11650
      • Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares
    • Mexico City, Distrito Federal, Mexico, 03100
      • RM Pharma Specialists
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Unidad de Investigación Clínica y Atención Médica HEPA
    • Guadalajara, Jalisco, Mexico, 44670
      • Private Practice - Dr. Arechavaleta Granell Maria del Rosario
  • Nuevo León
    • San Nicolas de los Garza, Nuevo León, Mexico, 66450
      • Servicios Integrales Nova de Monterrey S.A. de C.V.
    • San Nicolás de los Garza, Nuevo León, Mexico, 66465
      • Unidad Médica para la Salud Integral
• Puerto Rico
  • Hato Rey, Puerto Rico, 00917
    • Puerto Rico Medical Research Center
• Taiwan
  • Taichung, Taiwan, 404332
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
• United States
  • California
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research
  • Florida
    • Brandon, Florida, United States, 33511
      • Teradan Clinical Trials, LLC
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research Inc
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Brengle Family Medicine
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research
  • Ohio
    • Canton, Ohio, United States, 44718
      • NeuroScience Research Center
    • Cincinnati, Ohio, United States, 45212
      • CTI-CRC
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15236
      • Office 18
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Beaumont, Texas, United States, 77702
      • Gadolin Research
    • El Paso, Texas, United States, 79912
      • Advanced Neuro Research Center - ANRC
    • Red Oak, Texas, United States, 75154
      • Epic Medical Research
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy Research Center
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Placebo Comparator: Placebo_GPI1; Participants not on PAP therapy received placebo QW as an SC injection for 52 weeks.	Drug: Placebo; Administered SC
Experimental: 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	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Placebo Comparator: Placebo_GPI2; Participants who are on PAP therapy received placebo QW as an SC injection for 52 weeks.	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Apnea-Hypopnea Index (AHI)	Percent Change From Baseline in AHI was evaluated.	Baseline, Week 52
Percentage of Participants With ≥50% AHI Reduction From Baseline	Percentage of participants achieving ≥50% AHI reduction from baseline to Week 52 was evaluated.	Week 52
Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10	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.	Week 52
Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour)	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.	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)	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).	Baseline, Week 52
Percent Change From Baseline in Body Weight	Percent Change from Baseline in Body Weight was evaluated.	Baseline, Week 52
Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration	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.	Baseline, Week 52
Change From Baseline in Systolic Blood Pressure (SBP)	Change in systolic blood pressure from baseline to Week 48 was evaluated.	Baseline, Week 48

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2022
• Primary Completion (Actual): March 12, 2024
• Study Completion (Actual): March 29, 2024

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 12, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Nutrition Disorders; Overnutrition; Body Weight; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Overweight; Sleep Disorders, Intrinsic; Dyssomnias; Obesity; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: 18357; I8F-MC-GPIF (Other Identifier: Eli Lilly and Company); I8F-MC-GPI1 (Other Identifier: Eli Lilly and Company); I8F-MC-GPI2 (Other Identifier: Eli Lilly and Company); 2021-004552-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No