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

NCT05412004 | Completed Phase 3 Results DMC FDA Drug

• 5 other identifiers: 18357I8F-MC-GPIFI8F-MC-GPI1I8F-MC-GPI22021-004552-41
• Study Type: interventional
• Target: 469
• Locations: 10 countries
• Sites: 58

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.

Conditions

Obstructive Sleep Apnea; Obesity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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

Study Arms (4)

Tirzepatide MTD_GPI1

EXPERIMENTAL

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

Placebo_GPI1

PLACEBO COMPARATOR

Participants not on PAP therapy received placebo QW as an SC injection for 52 weeks.

Drug: Placebo

Tirzepatide MTD_GPI2

EXPERIMENTAL

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

Placebo_GPI2

PLACEBO COMPARATOR

Participants who are on PAP therapy received placebo QW as an SC injection for 52 weeks.

Drug: Placebo

Interventions

Tirzepatide DRUG

Administered SC

Also known as: LY3298176

Tirzepatide MTD_GPI1; Tirzepatide MTD_GPI2

Placebo DRUG

Administered SC

Placebo_GPI1; Placebo_GPI2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (58)

Artemis Institute for Clinical Research

Riverside, California, 92503, United States

Location

Teradan Clinical Trials, LLC

Brandon, Florida, 33511, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Palm Beach Research Center

West Palm Beach, Florida, 33409, United States

Location

NeuroTrials Research Inc

Atlanta, Georgia, 30328, United States

Location

Rocky Mountain Clinical Research

Idaho Falls, Idaho, 83404, United States

Location

Brengle Family Medicine

Indianapolis, Indiana, 46260, United States

Location

Lillestol Research

Fargo, North Dakota, 58104, United States

Location

NeuroScience Research Center

Canton, Ohio, 44718, United States

Location

CTI-CRC

Cincinnati, Ohio, 45212, United States

Location

Office 18

Pittsburgh, Pennsylvania, 15236, United States

Location

Preferred Primary Care Physicians

Uniontown, Pennsylvania, 15401, United States

Location

FutureSearch Trials of Neurology

Austin, Texas, 78731, United States

Location

Gadolin Research

Beaumont, Texas, 77702, United States

Location

Advanced Neuro Research Center - ANRC

El Paso, Texas, 79912, United States

Location

Epic Medical Research

Red Oak, Texas, 75154, United States

Location

Sleep Therapy Research Center

San Antonio, Texas, 78229, United States

Location

Rainier Clinical Research Center

Renton, Washington, 98057, United States

Location

Woolcock Institute of Medical Research

Sydney, New South Wales, 2037, Australia

Location

Flinders University

Bedford Park, South Australia, 5042, Australia

Location

Núcleo de Pesquisa Clínica do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, 90430-001, Brazil

Location

CPCLIN

São Paulo, São Paulo, 01228-200, Brazil

Location

CPQuali Pesquisa Clínica

São Paulo, 01228-000, Brazil

Location

Hospital das Clinicas FMUSP

São Paulo, 04266-010, Brazil

Location

BR Trials - Ensaios Clinicos e Consultoria

São Paulo, 05003-090, Brazil

Location

Hospital das Clinicas FMUSP

São Paulo, 05403-000, Brazil

Location

The Second Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210011, China

Location

Wuxi People's Hospital

Wuxi, Jiangsu, 214023, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Zhongshan Hospital,Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

Vseobecna fakultni nemocnice v Praze

Prague, 12808, Czechia

Location

Praglandia s.r.o

Prague, 150 00, Czechia

Location

Siteworks GmbH

Hanover, Lower Saxony, 30449, Germany

Location

InnoDiab Forschung Gmbh

Essen, North Rhine-Westphalia, 45136, Germany

Location

Institut für Diabetesforschung GmbH Münster

Münster, North Rhine-Westphalia, 48145, Germany

Location

RED-Institut GmbH

Oldenburg in Holstein, Schleswig-Holstein, 23758, Germany

Location

Lungenpraxis Schleswig

Schleswig, Schleswig-Holstein, 24837, Germany

Location

Advanced Sleep Research

Berlin, 10117, Germany

Location

Diabeteszentrum Hamburg West

Hamburg, 22607, Germany

Location

Koujunkai Daido Clinic

Nagoya, Aichi-ken, 457-8511, Japan

Location

Kirigaokatsuda Hospital

Kitakyushu, Fukuoka, 802-0052, Japan

Location

RESM Respiratory and Sleep Medical Care Clinic

Yokohama, Kanagawa, 222-0033, Japan

Location

Sakai City Medical Center

Sakai, Osaka, 593-8304, Japan

Location

Fukuwa Clinic

Chuo-ku, Tokyo, 104-0031, Japan

Location

Osaka Kaisei Hospital

Osaka, 532-0003, Japan

Location

Private Practice - Dr. Arechavaleta Granell Maria del Rosario

Guadalajara, Jalisco, 44670, Mexico

Location

Unidad de Investigación Clínica y Atención Médica HEPA

Guadalajara, Jalisco, 44670, Mexico

Location

RM Pharma Specialists

Mexico City, Mexico City, 03100, Mexico

Location

Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares

Mexico City, Mexico City, 11650, Mexico

Location

Servicios Integrales Nova de Monterrey S.A. de C.V.

San Nicolás de los Garza, Nuevo León, 66450, Mexico

Location

Unidad Médica para la Salud Integral

San Nicolás de los Garza, Nuevo León, 66465, Mexico

Location

Investigacion En Salud Y Metabolismo Sc

Chihuahua City, 31217, Mexico

Location

Arké SMO S.A de C.V

Veracruz, 91910, Mexico

Location

Puerto Rico Medical Research Center

Hato Rey, Puerto Rico, 00917, Puerto Rico

Location

China Medical University Hospital

Taichung, 404332, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Related Publications (5)

• Malhotra A, Grunstein R, Azarbarzin A, Sands S, Somers VK, Aronne LJ, Jastreboff AM, Lou J, Chakladar S, Dunn JP, Bunck MC, Bednarik J. Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial. Nat Med. 2026 Jan 15. doi: 10.1038/s41591-025-04071-1. Online ahead of print.

  PMID: 41540105 DERIVED

• Malhotra A, Grunstein RR, Azarbarzin A, Sands SA, Dang X, Chakladar S, Dunn JP, Falcon B, Bednarik J. Tirzepatide for sleep-disordered breathing in SURMOUNT-OSA: Time course and association with body weight. Sleep Med. 2025 Dec;136:106853. doi: 10.1016/j.sleep.2025.106853. Epub 2025 Oct 14.

  PMID: 41135142 DERIVED

• Kanu C, Shinde S, Chakladar S, Dennehy EB, Weaver TE, Poon JL, Malhotra A. Effect of tirzepatide treatment on patient-reported outcomes among SURMOUNT-OSA participants with obstructive sleep apnea and obesity. Sleep Med. 2025 Oct;134:106719. doi: 10.1016/j.sleep.2025.106719. Epub 2025 Aug 6.

  PMID: 40774158 DERIVED

• Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A, Sands SA, Schwab RJ, Dunn JP, Chakladar S, Bunck MC, Bednarik J; SURMOUNT-OSA Investigators. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med. 2024 Oct 3;391(13):1193-1205. doi: 10.1056/NEJMoa2404881. Epub 2024 Jun 21.

  PMID: 38912654 DERIVED

• Malhotra A, Bednarik J, Chakladar S, Dunn JP, Weaver T, Grunstein R, Fietze I, Redline S, Azarbarzin A, Sands SA, Schwab RJ, Bunck MC. Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial. Contemp Clin Trials. 2024 Jun;141:107516. doi: 10.1016/j.cct.2024.107516. Epub 2024 Mar 26.

  PMID: 38547961 DERIVED

Related Links

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

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Obesity

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-459-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2022
• First Posted: June 9, 2022
• Study Start: June 21, 2022
• Primary Completion: March 12, 2024
• Study Completion: March 29, 2024
• Last Updated: April 30, 2025
• Results First Posted: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

ME (8); PR (1); US (18); BR (6); DE (7); CZ (2); CN (6); JP (6); TW (2); AU (2)