Clinical trial NCT06649045: A Master Protocol for Orforglipron in Participants With Obstructive Sleep Apnea and Obesity or Overweight
Official title: 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: OSA
Overweight or Obesity
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-10-18
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in Apnea-Hypopnea Index (AHI)
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Percent Change from Baseline in AHI
timeFrame: Baseline to Week 52
measure: Change from Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% min/hour)
timeFrame: Baseline to Week 52
measure: Change from Baseline in Patient-Reported Outcome Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a T-score
timeFrame: Baseline to Week 52
measure: Percentage of Participants Achieving ≥50% AHI Reduction
timeFrame: Baseline to Week 52
measure: Percent of Participants with AHI<5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10
timeFrame: Baseline to Week 52
measure: Percent Change from Baseline in Body Weight
timeFrame: Baseline to Week 52
measure: Change from Baseline in high-sensitivity C reactive protein (hsCRP) Concentration
timeFrame: Baseline to Week 52
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Ark Clinical Research
state: California
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Aurora
country: United States
facility: Care Access - Aurora
state: Colorado
city: Snellville
country: United States
facility: EBGS Clinical Research Center
state: Georgia
city: Blackfoot
country: United States
facility: Elite Clinical Trials
state: Idaho
city: Springfield
country: United States
facility: Central Illinois Diabetes and Clinical Research a Division of Prairie Education and Research Cooperative
state: Illinois
city: Shreveport
country: United States
facility: Care Access - Shreveport
state: Louisiana
city: Albuquerque
country: United States
facility: The Sleep Spot - Maimonides
state: New Mexico
city: Wilmington
country: United States
facility: Accellacare - Wilmington
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Preferred Clinical Research (Ofc 18)
state: Pennsylvania
city: Uniontown
country: United States
facility: Preferred Primary Care Physicians
state: Pennsylvania
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: Flower Mound
country: United States
facility: Prime Revival Research Institute, LLC
state: Texas
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Buenos Aires
country: Argentina
facility: Centro Médico Viamonte
state: Ciudad Autónoma De Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Consultorio de Investigación Clínica EMO SRL
state: Ciudad Autónoma De Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada
state: Ciudad Autónoma De Buenos Aires
city: Río Cuarto
country: Argentina
facility: Instituto Médico Río Cuarto
state: Córdoba
city: Paraná
country: Argentina
facility: Centro Privado de Medicina Respiratoria
state: Entre Ríos
city: Santa Rosa
country: Argentina
facility: Centro de Salud e Investigaciones Médicas
state: La Pampa
city: Rosario
country: Argentina
facility: INECO Neurociencias Oroño
state: Santa Fe
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME)
city: Porto Alegre
country: Brazil
facility: Núcleo de Pesquisa Clínica do Rio Grande do Sul
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: BR Trials - Ensaios Clinicos e Consultoria
state: São Paulo
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clínica
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigação Clínica
city: São Paulo
country: Brazil
facility: Hospital das Clinicas FMUSP
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Shenzhen
country: China
facility: ShenZhen People's Hospital
state: Guangdong
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Luoyang Shi
country: China
facility: The First Affiliated Hospital of Henan University of Science &Technology
state: Henan
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Pudong New Area People's Hospital Shanghai
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Huzhou
country: China
facility: Huzhou Central Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital
state: Zhejiang
city: Benesov
country: Czechia
facility: Nemocnice Rudolfa a Stefanie Benešov
state: Benešov
city: Praha
country: Czechia
facility: Milan Kvapil s.r.o., Diabetologicka ambulance
state: Praha 4
city: Praha 5
country: Czechia
facility: Praglandia s.r.o
city: Karlsruhe
country: Germany
facility: Siteworks - Karlsruhe
state: Baden-Württemberg
city: Bamberg
country: Germany
facility: CIMS Studienzentrum Bamberg
state: Bayern
city: Hannover
country: Germany
facility: Siteworks GmbH - Hannover
state: Niedersachsen
city: Essen
country: Germany
facility: InnoDiab Forschung Gmbh
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Unterfrintroper Hausarztzentrum Klinische Forschung
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Institut für Diabetesforschung GmbH Münster
state: Nordrhein-Westfalen
city: Oldenburg
country: Germany
facility: RED-Institut GmbH
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Advanced Sleep Research
city: Guntur
country: India
facility: Endolife Speciality Hospitals
state: Andhra Pradesh
city: Raipur
country: India
facility: All India Institute of Medical Sciences
state: Chhattisgarh
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
city: Bengaluru
country: India
facility: SDS Tuberculosis Research Center & Rajiv Gandhi Institute of Chest Diseases
state: Karnataka
city: Bengaluru
country: India
facility: St. Johns Medical College Hospital
state: Karnataka
city: Nagpur
country: India
facility: Sleep & Snoring Clinic & Research Centre
state: Maharashtra
city: Pune
country: India
facility: Villoo Poonawalla Memorial Hospital
state: Maharashtra
city: Thane
country: India
facility: Bhakti Vedanta Hospital and Research Institute
state: Maharashtra
city: Rishikesh
country: India
facility: All India Institute of Medical Sciences - Rishikesh
state: Uttarakhand
city: Kitakyushu
country: Japan
facility: Kirigaokatsuda Hospital
state: Fukuoka
city: Yokohama
country: Japan
facility: RESM Respiratory and Sleep Medical Care Clinic
state: Kanagawa
city: Urasoe
country: Japan
facility: Nakamura Clinic
state: Okinawa
city: Sakai
country: Japan
facility: Sakai City Medical Center
state: Osaka
city: Osaka
country: Japan
facility: Osaka Kaisei Hospital
city: Mexicali
country: Mexico
facility: Centro de Investigacion en Artritis y Osteoporosis SC
state: Baja California
city: Mexico City
country: Mexico
facility: RM Pharma Specialists - Unidad Especializada en Datos
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Centro Especializado En Diabetes, Obesidad Y Prevencion De Enfermedades Cardiovasculares
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Diseno y Planeacion en Investigacion Medica
state: Jalisco
city: Guadalajara
country: Mexico
facility: Private Practice - Dr. Arechavaleta Granell Maria del Rosario
state: Jalisco
city: Monterrey
country: Mexico
facility: CEINV Salud
state: Nuevo León
city: Monterrey
country: Mexico
facility: Centro de investigación y control metabólico
state: Nuevo León
city: Chihuahua
country: Mexico
facility: Enclifar Ensayos Clínicos Farmacológicos Sc
city: Chiayi City
country: Taiwan
facility: Chiayi Christian Hospital
state: Chiayi
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation-Linkou Branch
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: