Clinical trial NCT05929066: A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight
Official title: A Master Protocol to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (TRIUMPH-1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Obesity
Overweight
Osteoarthritis, Knee
Obstructive Sleep Apnea
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2023-07-03
Enrollment: 2300
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: The purpose of this study is to evaluate the efficacy and safety of retatrutide in participants who have obesity or overweight (J1I-MC-GZBJ master protocol) including subsets of participants who have knee osteoarthritis (OA) (J1I-MC-GOA1) or who have obstructive sleep apnea (OSA) (J1I-MC-GSA1). This study will last about 89 weeks and will include up to 24 visits. Addendum (2) is optional and available to approximately 500 participants to continue treatment with retatrutide for up to an additional 24 weeks.


Eligibility criteria: Inclusion Criteria:

* Have body mass index (BMI) ≥30.0 kilograms per square meter (kg/m²), or ≥27.0 kg/m² with at least one of the following:

  * hypertension
  * dyslipidemia
  * obstructive sleep apnea, or
  * cardiovascular disease
* History of of at least one unsuccessful dietary effort to reduce body weight

GOA1 Inclusion Criteria:

* Have index knee pain for \>12 weeks prior to screening, and presence of index knee pain for \>15 days over the previous month
* Have knee X-ray with moderate radiographic changes (Kellgren-Lawrence Grade 2 or 3) per central reading at screening
* Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA.

GSA1 Inclusion Criteria:

* Previously diagnosed with OSA
* Have AHI ≥15 on polysomnography at screening (definition of moderate-to-severe OSA)
* For participants not on positive airway pressure (PAP) therapy: unable or unwilling to use PAP therapy and have not used PAP for at least 4 weeks prior to screening.
* If on PAP therapy, have been on PAP therapy for at least 3 consecutive months prior to screening, and willing to temporarily stop using PAP therapy for approximately 7 days prior to each of the sleep study (PSG) visits.

GZBJ Addenda (2) inclusion criteria:

* Have completed the final treatment visit of GZBJ Week 80.

Exclusion Criteria:

* Have a self-reported or documented change in body weight \>5 kg (11 pounds) within 90 days.
* Have taken weight loss drugs, including over-the-counter medications, within 90 days prior to screening.
* Have a prior or planned surgical treatment for obesity.
* Have diabetes mellitus.
* Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
* Have had pancreatitis.

GOA1 exclusion criteria

* Have had steroid joint injections within 90 days of screening.
* Have had other joint injections and procedures within 6 months of screening.
* Have joint disease other than osteoarthritis.

GSA1 exclusion criteria

* Use stimulants (for example, modafinil, armodafinil, solriamfetol, pitolisant, amphetamine) less than 3 months prior to screening.
* Use hypnotics, mirtazapine, opioids, trazodone, and zonisamide less than 3 months prior to screening.
* Use a dental appliance or other device to treat OSA other than PAP therapy.

GZBJ Addenda (2) exclusion criteria

* Have had study intervention discontinuation.
* Have had permanent dose reduction.

Primary outcomes:
measure: Percent Change From Baseline in Body Weight
timeFrame: Baseline, Week 80
measure: Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score for GOA1 Subset
timeFrame: Baseline, Week 80
measure: Change from Baseline in Apnea-Hypopnea Index (AHI) Events Per Hour for GSA1 Subset
timeFrame: Baseline, Week 80
measure: Percent Change from Baseline in Body Weight to
timeFrame: Baseline, Week 104
Secondary outcomes:
measure: Change from Baseline in Body Mass Index (BMI)
timeFrame: Baseline, Week 80
measure: Change from Baseline in Waist Circumference
timeFrame: Baseline, Week 80
measure: Change from Baseline in Systolic Blood Pressure (SBP)
timeFrame: Baseline, Week 80
measure: Percent Change form Baseline in Fasting Insulin
timeFrame: Baseline, Week 80
measure: Change from Baseline in HbA1c
timeFrame: Baseline, Week 80
measure: Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score
timeFrame: Baseline, Week 80
measure: Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC)
timeFrame: Baseline through Week 80
measure: Change from Baseline in the WOMAC Physical Function Subscale Score for GOA1 Subset
timeFrame: Baseline, Week 80
measure: Change from Baseline in Average Pain Intensity Numeric Rating Scale (API-NRS) Score for GOA1 Subset
timeFrame: Baseline, Week 80
measure: Change from Baseline in Worst Pain Intensity Numeric Rating Scale (WPI-NRS) Score for GOA1 Subset
timeFrame: Baseline, Week 80
measure: Percent Change from Baseline in AHI for GSA1 Subset
timeFrame: Baseline, Week 80
measure: A Hierarchical Combination of Functional Outcomes of Sleep Questionnaire (FOSQ) 10 Score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score for GSA1 Subset
timeFrame: Baseline to Week 80
measure: Percentage of Participants with ≥50% AHI Reduction from Baseline for GSA1 Subset
timeFrame: Baseline to Week 80
measure: Percentage of Participants with AHI <5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10 for GSA1 Subset
timeFrame: Week 80
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Central Phoenix Medical Clinic
state: Arizona
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Little Rock
country: United States
facility: Medical Investigations
state: Arkansas
city: Fresno
country: United States
facility: Neuro-Pain Medical Center
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Brandon
country: United States
facility: Teradan Clinical Trials, LLC
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc
state: Georgia
city: Woodstock
country: United States
facility: North Georgia Clinical Research
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Diabetes and Clinical Research a Division of Prairie Education and Research Cooperative
state: Illinois
city: Indianapolis
country: United States
facility: Brengle Family Medicine
state: Indiana
city: Topeka
country: United States
facility: Cotton O'Neil Diabetes & Endocrinology
state: Kansas
city: Waltham
country: United States
facility: MedVadis Research Corporation
state: Massachusetts
city: Bay City
country: United States
facility: Great Lakes Research Group, Inc.
state: Michigan
city: Saint Peters
country: United States
facility: StudyMetrix Research
state: Missouri
city: Springfield
country: United States
facility: Clinvest Research LLC
state: Missouri
city: Las Vegas
country: United States
facility: Palm Research Center Tenaya
state: Nevada
city: Rochester
country: United States
facility: Rochester Clinical Research, LLC
state: New York
city: Morehead City
country: United States
facility: Carteret Medical Group
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates - Wilmington - Floral Parkway
state: North Carolina
city: Fargo
country: United States
facility: Lillestol Research
state: North Dakota
city: Duncansville
country: United States
facility: Altoona Center For Clinical Research
state: Pennsylvania
city: Greenville
country: United States
facility: Tribe Clinical Research, LLC
state: South Carolina
city: Spartanburg
country: United States
facility: Tribe Clinical Research - Spartanburg
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Health One Hundred Oaks
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: Houston
country: United States
facility: Juno Research
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Renton
country: United States
facility: Rainier Clinical Research Center
state: Washington
city: Botany
country: Australia
facility: Emeritus Research
state: New South Wales
city: Merewether
country: Australia
facility: The AIM Centre / Hunter Diabetes Centre
state: New South Wales
city: Meadowbrook
country: Australia
facility: Logan Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Fusion Clinical Research
state: South Australia
city: Adelaide
country: Australia
facility: Nightingale Research
state: South Aust
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research
state: Western Australia
city: Sao Paulo
country: Brazil
facility: CPCLIN
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: Brampton
country: Canada
facility: Aggarwal and Associates Limited
state: Ontario
city: Hamilton
country: Canada
facility: Dr. Steven V. Zizzo Medicine Professional Corporation
state: Ontario
city: Hamilton
country: Canada
facility: Wharton Medical Clinic
state: Ontario
city: Niagara Falls
country: Canada
facility: Your Research Network
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc.
state: Ontario
city: Toronto
country: Canada
facility: Canadian Phase Onward
state: Ontario
city: Laval
country: Canada
facility: Centre de Recherche Clinique de Laval
state: Quebec
city: Montreal
country: Canada
facility: Clinique de médecine Urbaine du Quartier Latin
state: Quebec
city: Trois-Rivières
country: Canada
facility: C.I.C. Mauricie inc.
state: Quebec
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
state: Csongrád
city: Szekesfehervar
country: Hungary
facility: Regia Med Kft
state: Fejér
city: Nyiregyhaza
country: Hungary
facility: Medifarma 98 Kft
state: Nyíregyháza
city: Balatonfüred
country: Hungary
facility: DRC Gyógyszervizsgáló Központ
state: Veszprém
city: Budapest
country: Hungary
facility: Óbudai Egészségügyi Centrum
city: Budapest
country: Hungary
facility: ClinDiab Kft.
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Guntur
country: India
facility: Endolife Speciality Hospitals
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Avron Hospitals
state: Gujarat
city: Surat
country: India
facility: Surat Institute of Digestive Sciences Hospitals
state: Gujarat
city: Hubli
country: India
facility: Karnataka Institute of Medical Sciences
state: Karnataka
city: Thiruvananthapuram
country: India
facility: Indian Institute of Diabetes
state: Kerala
city: Trivandrum
country: India
facility: Jothydev's Diabetes and Research Center
state: Kerala
city: Mumbai
country: India
facility: Wockhardt Hospital - Mumbai Central
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
state: Maharashtra
city: Pune
country: India
facility: Chellaram Diabetes Institute
state: Maharashtra
city: Pune
country: India
facility: Lifepoint Multispeciality Hospital
state: Maharashtra
city: Bhubaneswar
country: India
facility: All India Institute of Medical Sciences
state: Odisha
city: Jaipur
country: India
facility: Eternal Heart Care Center and Research Institute
state: Rajasthan
city: Vellore
country: India
facility: Christian Medical College Vellore
state: Tamil Nadu
city: Kolkata
country: India
facility: ILS Hospitals
state: West Benga
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
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Clinica Omega
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Diseno y Planeacion en Investigacion Medica
state: Jalisco
city: Guadalajara
country: Mexico
facility: Clinica de Investigacion en Reumatologia y Obesidad S. C.
state: Jalisco
city: Guadalajara
country: Mexico
facility: Private Practice - Dr. Arechavaleta Granell Maria del Rosario
state: Jalisco
city: Guadalajara
country: Mexico
facility: Unidad de Investigación Clínica y Atención Médica HEPA
state: Jalisco
city: Cuernavaca
country: Mexico
facility: Instituto de Diabetes, Obesidad y Nutricion
state: Morelos
city: Monterrey
country: Mexico
facility: Unidad biomedica avanzada monterrey
state: Nuevo León
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: Nuevo León
city: Mérida
country: Mexico
facility: EME RED Hospitalaria
state: Yucatán
city: Mérida
country: Mexico
facility: Kohler and Milstein Research S.A. de C.V.
state: Yucatán
city: Aguascalientes
country: Mexico
facility: Centro de Atención e Investigación Clínica
city: Chihuahua
country: Mexico
facility: Investigacion En Salud Y Metabolismo S.C / Nutricion Clinica / Unidad de Base de Datos
city: Veracruz
country: Mexico
facility: Arké SMO S.A de C.V
city: Bydgoszcz
country: Poland
facility: INTERCOR
state: Kujawsko-pomorskie
city: Lublin
country: Poland
facility: CenterMed Lublin NZOZ
state: Lubelskie
city: Lublin
country: Poland
facility: Gabinety TERPA
state: Lubelskie
city: Warszawa
country: Poland
facility: MICS Centrum Medyczne Warszawa
state: Mazowieckie
city: Tarnów
country: Poland
facility: Private Practice - Dr. Robert Witek
state: Małopolskie
city: Białystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Białymstoku
state: Podlaskie
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych PI-House sp. z o.o.
state: Pomorskie
city: Elblag
country: Poland
facility: Centrum Kliniczno-Badawcze
state: Warmińsko-mazurskie
city: Elbląg
country: Poland
facility: Ambulatorium Sp. z o.o.
state: Warmińsko-mazurskie
city: Poznań
country: Poland
facility: Centrum Zdrowia Metabolicznego Pawel Bogdanski
state: Wielkopolskie
city: Katowice
country: Poland
facility: NZOZ Salvia CM
state: Śląskie
city: Kielce
country: Poland
facility: Specjalistyczna Praktyka Lekarska Diabetologia, Leczenie Cukrzycy i Otylosci
state: Świętokrzyskie
city: Ponce
country: Puerto Rico
facility: Ponce Medical School Foundation Inc.
city: Oradea
country: Romania
facility: Diabdana
state: Bihor
city: Brasov
country: Romania
facility: C.M.D.T.A. Neomed
state: Brașov
city: Bucharest
country: Romania
facility: Hightech Medical Services SRL-Centrul pentru Studiul Metabolismului
state: București
city: Mangalia
country: Romania
facility: Gama Diamed
state: Constanța
city: Timisoara
country: Romania
facility: Cabinet Medical Dr.Geru
state: Timiș
city: Bacău
country: Romania
facility: SC Minimed SRL
city: Galați
country: Romania
facility: Diamed Obesity
city: Iași
country: Romania
facility: Centrul Medical Consultmed
city: Satu Mare
country: Romania
facility: Clinica Korall
city: Sibiu
country: Romania
facility: Policlinica Astra Sibiu
city: A Coruña
country: Spain
facility: CHUAC-Complejo Hospitalario Universitario A Coruña
state: A Coruña [La Coruña]
city: Ferrol
country: Spain
facility: Complejo Hospitalario Universitario de Ferrol (CHUF)- Hospital Naval
state: A Coruña [La Coruña]
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
state: Valenciana, Comunitat
city: Sevilla
country: Spain
facility: Clínica nuevas Tecnologías en Diabetes y Endocrinología (NTDE)
city: Chippenham
country: United Kingdom
facility: Rowden Surgery
state: England
city: Blackpool
country: United Kingdom
facility: Layton Medical Centre
state: Lancashire
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
state: Leicestershire
city: Enfield
country: United Kingdom
facility: Panthera Biopartners - North London
state: London, City Of
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
state: Scotland
city: Birmingham
country: United Kingdom
facility: Heartlands Hospital
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital NHS Foundation Trust
city: Penzance
country: United Kingdom
facility: St Clare Medical Centre
city: Sheffield
country: United Kingdom
facility: Panthera Biopartners - Sheffield
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: