A Master Protocol for Orforglipron in Participants With Obstructive Sleep Apnea and Obesity or Overweight (ATTAIN-OSA)

A 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 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.

Study Overview

• Status: Active, not recruiting
• Conditions: OSA; Overweight or Obesity
• Intervention / Treatment: Drug: Placebo; Drug: Orforglipron

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1120AAC
    • Centro Médico Viamonte
  • Buenos Aires, Argentina, C1056ABI
    • Centro de Investigaciones Metabólicas (CINME)
  • Buenos Aires, Argentina, C1405BUB
    • Consultorio de Investigacion Clinica EMO SRL
  • Buenos Aires, Argentina, C1425AGC
    • Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
  • Paraná, Argentina, 3100
    • Centro Privado de Medicina Respiratoria
  • Rosario, Argentina, 2000
    • INECO Neurociencias Oroño
  • Río Cuarto, Argentina, X5800AEV
    • Instituto Médico Río Cuarto
  • Santa Rosa, Argentina, L6300
    • Centro de Salud e Investigaciones Médicas
• Brazil
  • Porto Alegre, Brazil, 90430-001
    • Núcleo de Pesquisa Clínica do Rio Grande do Sul
  • São Paulo, Brazil, 01228-000
    • CPQuali Pesquisa Clínica
  • São Paulo, Brazil, 04266-010
    • CEPIC - Centro Paulista de Investigacao Clinica
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas FMUSP
  • São Paulo, Brazil, 01236030
    • Br Trials - Ensaios Clínicos e Consultoria
• China
  • Beijing, China, 100034
    • Peking University People's Hospital
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Chengdu, China, 610072
    • Sichuan Provincial People's Hospital
  • Harbin, China, 150001
    • The Fourth Affiliated Hospital of Harbin Medical University
  • Huzhou, China, 313000
    • Huzhou Central Hospital
  • Luoyang Shi, China, 471003
    • The First Affiliated Hospital of Henan University of Science &Technology
  • Nanchang, China, 330006
    • Jiangxi Provincial People's Hospital
  • Ningbo, China, 315010
    • Ningbo First Hospital
  • Shanghai, China, 201200
    • Pudong New Area People's Hospital Shanghai
  • Shenzhen, China, 518020
    • Shenzhen People's Hospital
  • Wuxi, China, 214023
    • Wuxi People's Hospital
• Czechia
  • Benešov, Czechia, 256 01
    • Nemocnice Rudolfa a Stefanie Benešov
  • Prague, Czechia, 14900
    • Milan Kvapil s.r.o., Diabetologicka ambulance
  • Prague, Czechia, 150 00
    • Praglandia s.r.o
• Germany
  • Bamberg, Germany, 96049
    • CIMS Studienzentrum Bamberg
  • Berlin, Germany, 10117
    • Advanced Sleep Research
  • Essen, Germany, 45136
    • InnoDiab Forschung GmbH
  • Essen, Germany, 45359
    • Unterfrintroper Hausarztzentrum Klinische Forschung
  • Hanover, Germany, 30449
    • Siteworks GmbH - Hannover
  • Karlsruhe, Germany, 76137
    • Siteworks - Karlsruhe
  • Münster, Germany, 48145
    • Institut für Diabetesforschung GmbH Münster
  • Oldenburg, Germany, 23758
    • Red-Institut GmbH
• Japan
  • Kitakyushu, Japan, 802-0052
    • Kirigaokatsuda Hospital
  • Osaka, Japan, 532-0003
    • Osaka Kaisei Hospital
  • Sakai, Japan, 593-8304
    • Sakai City Medical Center
  • Urasoe, Japan, 901-2132
    • Nakamura Clinic
  • Yokohama, Japan, 222-0033
    • RESM Respiratory and Sleep Medical Care Clinic
• Mexico
  • Chihuahua City, Mexico, 31110
    • Enclifar Ensayos Clínicos Farmacológicos Sc
  • Guadalajara, Mexico, 44130
    • Diseno y Planeacion en Investigacion Medica
  • Guadalajara, Mexico, 44670
    • Private Practice - Dr. Arechavaleta Granell Maria del Rosario
  • Mexicali, Mexico, 21200
    • Centro de Investigacion en Artritis y Osteoporosis SC
  • Mexico City, Mexico, 03100
    • RM Pharma Specialists - Unidad Especializada en Datos
  • Mexico City, Mexico, 11650
    • Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares
  • Monterrey, Mexico, 64020
    • CEINV Salud
• Taiwan
  • Chiayi City, Taiwan, 600
    • Chiayi Christian Hospital
  • Taichung, Taiwan, 404332
    • China Medical University Hospital
  • Tainan City, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taoyuan District, Taiwan, 333
    • Chang Gung Medical Foundation-Linkou Branch
• United States
  • California
    • Long Beach, California, United States, 90815
      • Ark Clinical Research
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Care Access - Aurora
  • Georgia
    • Snellville, Georgia, United States, 30078
      • EBGS Clinical Research Center
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Elite Clinical Trials
  • Louisiana
    • Shreveport, Louisiana, United States, 71105
      • Care Access - Shreveport
  • New Mexico
    • Albuquerque, New Mexico, United States, 87107
      • The Sleep Spot - Maimonides
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Accellacare - Wilmington
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians, Preferred Clinical Research (Ofc 18)
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Flower Mound, Texas, United States, 75028
      • Prime Revival Research Institute, LLC
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.; Other Names: LY3502970
Placebo Comparator: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Apnea-Hypopnea Index (AHI)	Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Percent Change from Baseline in Body Weight	Baseline to Week 52
Change from Baseline in high-sensitivity C reactive protein (hsCRP) Concentration	Baseline to Week 52

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

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 17, 2024
• First Submitted That Met QC Criteria: October 17, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Substandard Drugs; Pharmaceutical Preparations; orforglipron
• Other Study ID Numbers: 27226; J5P-MC-GZRA (Other Identifier: Eli Lilly and Company); J5P-MC-GZ01 (Other Identifier: Eli Lilly and Company); J5P-MC-GZ02 (Other Identifier: Eli Lilly and Company)

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