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

Phase 3

Active, not recruiting

• Conditions: OSA; Overweight or Obesity
• Interventions: Drug: Orforglipron; Drug: Placebo

• Registration Number: NCT06649045
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-10-17
• Study First Submitted QC: 2024-10-17
• Study First Posted: 2024-10-18
• Study Start: 2024-10-22
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-26
• Last Update Posted: 2025-09-29
• Primary Completion: 2026-11
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 600

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Orforglipron	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
Placebo	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

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Apnea-Hypopnea Index (AHI)	Baseline to Week 52

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (66)

Ark Clinical Research; 🇺🇸 Long Beach, California, United States

Peninsula Research Associates; 🇺🇸 Rolling Hills Estates, California, United States

Artemis Institute for Clinical Research; 🇺🇸 San Diego, California, United States

Care Access - Aurora; 🇺🇸 Aurora, Colorado, United States

EBGS Clinical Research Center; 🇺🇸 Snellville, Georgia, United States

Elite Clinical Trials; 🇺🇸 Blackfoot, Idaho, United States

Care Access - Shreveport; 🇺🇸 Shreveport, Louisiana, United States

The Sleep Spot - Maimonides; 🇺🇸 Albuquerque, New Mexico, United States

Accellacare - Wilmington; 🇺🇸 Wilmington, North Carolina, United States

CTI Clinical Research Center; 🇺🇸 Cincinnati, Ohio, United States

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