A Master Protocol for Orforglipron in Participants With Obstructive Sleep Apnea and Obesity or Overweight

NCT06649045 | Active Not Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: 27226J5P-MC-GZRAJ5P-MC-GZ01J5P-MC-GZ02
• Study Type: interventional
• Target: 600
• Locations: 9 countries
• Sites: 66

Brief Summary

Study GZRA is a master protocol that will support 2 independent studies, GZ01 and GZ02. Participants will be assigned to the appropriate study prior to randomization. The purpose of the studies is to evaluate the efficacy and safety of orforglipron in participants who have moderate-to-severe OSA and obesity or overweight. Study GZ01 will include participants who are unable or are unwilling to use PAP therapy. Study GZ02 will include participants who are on PAP therapy for at least 3 months at time of screening and plan to continue PAP therapy during the study.

Conditions

OSA; Overweight or Obesity

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Apnea-Hypopnea Index (AHI)

  Baseline to Week 52

Secondary Outcomes (7)

• Percent Change from Baseline in AHI

  Baseline to Week 52

• Change from Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% min/hour)

  Baseline to Week 52

• Change from Baseline in Patient-Reported Outcome Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a T-score

  Baseline to Week 52

• Percentage of Participants Achieving ≥50% AHI Reduction

  Baseline to Week 52

• Percent of Participants with AHI<5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10

  Baseline to Week 52

Study Arms (2)

Orforglipron

EXPERIMENTAL

Participants will receive orforglipron orally. Study 1 GZ01: Participants who are unable or unwilling to use PAP Study 2 GZ02: Participants who plan to continue PAP therapy

Drug: Orforglipron

Placebo

PLACEBO COMPARATOR

Participants will receive placebo orally. Study 1 GZ01: Participants who are unable or unwilling to use PAP Study 2 GZ02: Participants who plan to continue PAP therapy

Drug: Placebo

Interventions

Orforglipron DRUG

Administered orally.

Also known as: LY3502970

Orforglipron

Placebo DRUG

Administered orally.

Placebo

Eligibility Criteria

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

You may qualify if:

• have AHI ≥15 on PSG as part of the trial at screening (V1).
• have body mass index (BMI) ≥27 kg/m²
• Participants who are unable or unwilling to use PAP therapy.
• Participants must not have used PAP for at least 4 weeks prior to screening.
• Participants who have been on PAP therapy for at least 3 consecutive months prior to study start and plan to continue PAP therapy during the study.

You may not qualify if:

• Have Type 1 diabetes (T1D) or Type 2 diabetes (T2D), history of ketoacidosis, or hyperosmolar state/coma
• Have HbA1c ≥6.5% (≥ 48 mmol/mol), as determined by the central laboratory at Visit 1.
• Had any previous or planned upper airway surgery for sleep apnea or major ear, nose or throat surgery
• 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
• 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, abdominoplasty or cryolipolysis if performed more than 1 year prior to screening)
• Have a prior or planned endoscopic and/or present device-based therapy for obesity.
• Have obesity induced by other endocrinologic disorders or diagnosed monogenetic or syndromic forms of obesity.
• 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 study.
• Are unwilling to temporary discontinue PAP therapy for 7 days prior to PSG testing during the study.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (66)

Ark Clinical Research

Long Beach, California, 90815, United States

Location

Peninsula Research Associates

Rolling Hills Estates, California, 90274, United States

Location

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

Care Access - Aurora

Aurora, Colorado, 80012, United States

Location

EBGS Clinical Research Center

Snellville, Georgia, 30078, United States

Location

Elite Clinical Trials

Blackfoot, Idaho, 83221, United States

Location

Care Access - Shreveport

Shreveport, Louisiana, 71105, United States

Location

The Sleep Spot - Maimonides

Albuquerque, New Mexico, 87107, United States

Location

Accellacare - Wilmington

Wilmington, North Carolina, 28401, United States

Location

CTI Clinical Research Center

Cincinnati, Ohio, 45212, United States

Location

Preferred Primary Care Physicians, Preferred Clinical Research (Ofc 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

Prime Revival Research Institute, LLC

Flower Mound, Texas, 75028, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Centro de Investigaciones Metabólicas (CINME)

Buenos Aires, C1056ABI, Argentina

Location

Centro Médico Viamonte

Buenos Aires, C1120AAC, Argentina

Location

Consultorio de Investigación Clínica EMO SRL

Buenos Aires, C1405BUB, Argentina

Location

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

Buenos Aires, C1425AGC, Argentina

Location

Centro Privado de Medicina Respiratoria

Paraná, 3100, Argentina

Location

Instituto Médico Río Cuarto

Río Cuarto, X5800AEV, Argentina

Location

INECO Neurociencias Oroño

Rosario, 2000, Argentina

Location

Centro de Salud e Investigaciones Médicas

Santa Rosa, L6300, Argentina

Location

Núcleo de Pesquisa Clínica do Rio Grande do Sul

Porto Alegre, 90430-001, Brazil

Location

CPQuali Pesquisa Clínica

São Paulo, 01228-000, Brazil

Location

BR Trials - Ensaios Clinicos e Consultoria

São Paulo, 01236030, Brazil

Location

CEPIC - Centro Paulista de Investigação Clínica

São Paulo, 04266-010, Brazil

Location

Hospital das Clinicas FMUSP

São Paulo, 05403-000, Brazil

Location

Peking University People's Hospital

Beijing, 100034, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

Sichuan Provincial People's Hospital

Chengdu, 610072, China

Location

The Fourth Affiliated Hospital of Harbin Medical University

Harbin, 150001, China

Location

Huzhou Central Hospital

Huzhou, 313000, China

Location

The First Affiliated Hospital of Henan University of Science &Technology

Luoyang Shi, 471003, China

Location

Jiangxi Provincial People's Hospital

Nanchang, 330006, China

Location

Ningbo First Hospital

Ningbo, 315010, China

Location

Pudong New Area People's Hospital Shanghai

Shanghai, 201200, China

Location

ShenZhen People's Hospital

Shenzhen, 518020, China

Location

Wuxi People's Hospital

Wuxi, 214023, China

Location

Nemocnice Rudolfa a Stefanie Benešov

Benešov, 256 01, Czechia

Location

Milan Kvapil s.r.o., Diabetologicka ambulance

Prague, 14900, Czechia

Location

Praglandia s.r.o

Prague, 150 00, Czechia

Location

CIMS Studienzentrum Bamberg

Bamberg, 96049, Germany

Location

Advanced Sleep Research

Berlin, 10117, Germany

Location

InnoDiab Forschung Gmbh

Essen, 45136, Germany

Location

Unterfrintroper Hausarztzentrum Klinische Forschung

Essen, 45359, Germany

Location

Siteworks GmbH - Hannover

Hanover, 30449, Germany

Location

Siteworks - Karlsruhe

Karlsruhe, 76137, Germany

Location

Institut für Diabetesforschung GmbH Münster

Münster, 48145, Germany

Location

RED-Institut GmbH

Oldenburg, 23758, Germany

Location

Kirigaokatsuda Hospital

Kitakyushu, 802-0052, Japan

Location

Osaka Kaisei Hospital

Osaka, 532-0003, Japan

Location

Sakai City Medical Center

Sakai, 593-8304, Japan

Location

Nakamura Clinic

Urasoe, 901-2132, Japan

Location

RESM Respiratory and Sleep Medical Care Clinic

Yokohama, 222-0033, Japan

Location

Enclifar Ensayos Clínicos Farmacológicos Sc

Chihuahua City, 31110, Mexico

Location

Diseno y Planeacion en Investigacion Medica

Guadalajara, 44130, Mexico

Location

Private Practice - Dr. Arechavaleta Granell Maria del Rosario

Guadalajara, 44670, Mexico

Location

Centro de Investigacion en Artritis y Osteoporosis SC

Mexicali, 21200, Mexico

Location

RM Pharma Specialists - Unidad Especializada en Datos

Mexico City, 03100, Mexico

Location

Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares

Mexico City, 11650, Mexico

Location

CEINV Salud

Monterrey, 64020, Mexico

Location

Chiayi Christian Hospital

Chiayi City, 600, Taiwan

Location

China Medical University Hospital

Taichung, 404332, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Chang Gung Medical Foundation-Linkou Branch

Taoyuan District, 333, Taiwan

Location

MeSH Terms

Conditions

Overweight; Obesity

Interventions

orforglipron

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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

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: October 17, 2024
• First Posted: October 18, 2024
• Study Start: October 22, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: September 29, 2025

Record last verified: 2025-09

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

BR (5); JP (5); CN (11); TW (4); US (15); AR (8); ME (7); CZ (3); DE (8)