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

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified August 2025 by Eli Lilly and Company
Sponsor
Eli Lilly and Company
Information Provided by (Responsible Party)
Eli Lilly and Company
Clinicaltrials.gov Identifier
NCT06649045
Other Study ID Numbers:
27226
First Submitted
October 16, 2024
First Posted
October 17, 2024
Last Update Posted
September 28, 2025
Last Verified
August 2025

ClinicalTrials.gov processed this data on September 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
OSAOverweight or Obesity
Drug: OrforglipronDrug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment600 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA Master Protocol to Investigate the Efficacy and Safety of Orforglipron Once Daily in Participants Who Have Obstructive Sleep Apnea and Obesity or Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial
Study Start DateOctober 21, 2024
Actual Primary Completion Date5mos 1w from now
Actual Study Completion Date7mos 1w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Orforglipron
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
Administered orally.
Placebo
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
Administered orally.

Outcome Measures

Primary Outcome Measures
  1. Change from Baseline in Apnea-Hypopnea Index (AHI)
Secondary Outcome Measures
  1. Percent Change from Baseline in AHI
  2. Change from Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% min/hour)
  3. Change from Baseline in Patient-Reported Outcome Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a T-score
  4. Percentage of Participants Achieving ≥50% AHI Reduction
  5. Percent of Participants with AHI<5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10
  6. Percent Change from Baseline in Body Weight
  7. Change from Baseline in high-sensitivity C reactive protein (hsCRP) Concentration

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Master GZRA inclusion criteria
have AHI ≥15 on PSG as part of the trial at screening (V1).
have body mass index (BMI) ≥27 kg/m² Study 1 GZ01 inclusion criteria
Participants who are unable or unwilling to use PAP therapy.
Participants must not have used PAP for at least 4 weeks prior to screening. Study 2 GZ02 inclusion criteria
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.
Exclusion Criteria
Master GZRA exclusion criteria
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. Study 2 GZ02 exclusion criteria
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.

Contacts and Locations

Sponsors and CollaboratorsEli Lilly and Company
Locations
Ark Clinical Research | Long Beach California, United States, 90815Peninsula Research Associates | Rolling Hills Estates California, United States, 90274Artemis Institute for Clinical Research | San Diego California, United States, 92103Care Access - Aurora | Aurora Colorado, United States, 80012EBGS Clinical Research Center | Snellville Georgia, United States, 30078Elite Clinical Trials | Blackfoot Idaho, United States, 83221Care Access - Shreveport | Shreveport Louisiana, United States, 71105The Sleep Spot - Maimonides | Albuquerque New Mexico, United States, 87107Accellacare - Wilmington | Wilmington North Carolina, United States, 28401CTI Clinical Research Center | Cincinnati Ohio, United States, 45212Preferred Primary Care Physicians, Preferred Clinical Research (Ofc 18) | Pittsburgh Pennsylvania, United States, 15236Preferred Primary Care Physicians | Uniontown Pennsylvania, United States, 15401FutureSearch Trials of Neurology | Austin Texas, United States, 78731Prime Revival Research Institute, LLC | Flower Mound Texas, United States, 75028Northwest Clinical Research Center | Bellevue Washington, United States, 98007Centro de Investigaciones Metabólicas (CINME) | Buenos Aires , Argentina, C1056ABICentro Médico Viamonte | Buenos Aires , Argentina, C1120AACConsultorio de Investigación Clínica EMO SRL | Buenos Aires , Argentina, C1405BUBCentro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada | Buenos Aires , Argentina, C1425AGCCentro Privado de Medicina Respiratoria | Paraná , Argentina, 3100Instituto Médico Río Cuarto | Río Cuarto , Argentina, X5800AEVINECO Neurociencias Oroño | Rosario , Argentina, 2000Centro de Salud e Investigaciones Médicas | Santa Rosa , Argentina, L6300Núcleo de Pesquisa Clínica do Rio Grande do Sul | Porto Alegre , Brazil, 90430-001CPQuali Pesquisa Clínica | São Paulo , Brazil, 01228-000BR Trials - Ensaios Clinicos e Consultoria | São Paulo , Brazil, 01236030CEPIC - Centro Paulista de Investigação Clínica | São Paulo , Brazil, 04266-010Hospital das Clinicas FMUSP | São Paulo , Brazil, 05403-000Peking University People's Hospital | Beijing , China, 100034The First Hospital of Jilin University | Changchun , China, 130021Sichuan Provincial People's Hospital | Chengdu , China, 610072The Fourth Affiliated Hospital of Harbin Medical University | Harbin , China, 150001Huzhou Central Hospital | Huzhou , China, 313000The First Affiliated Hospital of Henan University of Science &Technology | Luoyang Shi , China, 471003Jiangxi Provincial People's Hospital | Nanchang , China, 330006Ningbo First Hospital | Ningbo , China, 315010Pudong New Area People's Hospital Shanghai | Shanghai , China, 201200ShenZhen People's Hospital | Shenzhen , China, 518020Wuxi People's Hospital | Wuxi , China, 214023Nemocnice Rudolfa a Stefanie Benešov | Benešov , Czechia, 256 01Milan Kvapil s.r.o., Diabetologicka ambulance | Prague , Czechia, 14900Praglandia s.r.o | Prague , Czechia, 150 00CIMS Studienzentrum Bamberg | Bamberg , Germany, 96049Advanced Sleep Research | Berlin , Germany, 10117InnoDiab Forschung Gmbh | Essen , Germany, 45136Unterfrintroper Hausarztzentrum Klinische Forschung | Essen , Germany, 45359Siteworks GmbH - Hannover | Hanover , Germany, 30449Siteworks - Karlsruhe | Karlsruhe , Germany, 76137Institut für Diabetesforschung GmbH Münster | Münster , Germany, 48145RED-Institut GmbH | Oldenburg , Germany, 23758Kirigaokatsuda Hospital | Kitakyushu , Japan, 802-0052Osaka Kaisei Hospital | Osaka , Japan, 532-0003Sakai City Medical Center | Sakai , Japan, 593-8304Nakamura Clinic | Urasoe , Japan, 901-2132RESM Respiratory and Sleep Medical Care Clinic | Yokohama , Japan, 222-0033Enclifar Ensayos Clínicos Farmacológicos Sc | Chihuahua City , Mexico, 31110Diseno y Planeacion en Investigacion Medica | Guadalajara , Mexico, 44130Private Practice - Dr. Arechavaleta Granell Maria del Rosario | Guadalajara , Mexico, 44670Centro de Investigacion en Artritis y Osteoporosis SC | Mexicali , Mexico, 21200RM Pharma Specialists - Unidad Especializada en Datos | Mexico City , Mexico, 03100Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares | Mexico City , Mexico, 11650CEINV Salud | Monterrey , Mexico, 64020Chiayi Christian Hospital | Chiayi City , Taiwan, 600China Medical University Hospital | Taichung , Taiwan, 404332National Cheng Kung University Hospital | Tainan , Taiwan, 704Chang Gung Medical Foundation-Linkou Branch | Taoyuan , Taiwan, 333
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