Clinical trial NCT06045221: A Study of Orforglipron (LY3502970) Compared With Semaglutide in Participants With Type 2 Diabetes Inadequately Controlled With Metformin
Official title: A Phase 3, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Once Daily Oral LY3502970 Compared With Oral Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin (ACHIEVE-3)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Type 2 Diabetes
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 1576
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 main purpose of this study is to assess efficacy and safety of orforglipron compared with oral semaglutide in participants with Type 2 diabetes and inadequate glycemic control with metformin.The study will last around 61 weeks.


Eligibility criteria: Inclusion Criteria:

* Have Type 2 Diabetes
* Have HbA1c ≥7.0% (53 mmol/mol) to ≤10.5% (91 mmol/mol), as determined by the central laboratory at screening.
* Have been on stable diabetes treatment with metformin ≥1500 milligram (mg)/day during the 90 days prior to screening and maintained through randomization.
* Are of stable body weight (±5%) for at least 90 days prior to screening and agree to not initiate an intensive diet or exercise program during the study with the intent of reducing body weight, other than the lifestyle and/or dietary measures for diabetes treatment

Exclusion Criteria:

* Have Type 1 Diabetes
* Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema, for example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor inhibitors.
* Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization.
* Have a New York Heart Association functional classification IV congestive heart failure.
* Have an estimated glomerular filtration rate (eGFR) \<45 milliliter/minute (mL/min)/1.73 square meter (m²) or lower than the country-specific threshold for discontinuing metformin therapy per local label as determined by the central laboratory at screening.
* Have a serum calcitonin level of ≥35 nanogram/Liter (ng/L), as determined by the central laboratory at screening.
* Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.

Primary outcomes:
measure: Change from Baseline in Hemoglobin A1c (HbA1c)
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Change from Baseline in HbA1c
timeFrame: Baseline, Week 52
measure: Percentage of Participants Who Achieved HbA1c <7.0% 53 millimole/mole (mmol/mol)
timeFrame: Week 52
measure: Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/mol)
timeFrame: Week 52
measure: Percentage Change from Baseline in Body Weight
timeFrame: Baseline, Week 52
measure: Change from Baseline in Body Weight
timeFrame: Baseline, Week 52
measure: Percentage of Participants Who Achieved HbA1c <5.7% (39 mmol/mol)
timeFrame: Week 52
measure: Change from Baseline in Fasting Serum Glucose
timeFrame: Baseline, Week 52
measure: Change from Baseline in Daily Average 7-point Self-monitored Blood Glucose (SMBG)
timeFrame: Baseline, Week 52
measure: Percentage of Participants Who Achieved Weight Loss of ≥5%
timeFrame: Week 52
measure: Percentage of Participants Who Achieved Weight Loss of ≥10%
timeFrame: Week 52
measure: Percentage of Participants Who Achieved Weight Loss of ≥15%
timeFrame: Week 52
measure: Change from Baseline in Systolic Blood Pressure (SBP)
timeFrame: Baseline, Week 52
measure: Change from Baseline in Diastolic Blood Pressure (DBP)
timeFrame: Baseline, Week 52
measure: Percentage Change from Baseline in Total Cholesterol
timeFrame: Baseline, Week 52
measure: Percentage Change from Baseline in High Density Lipoprotein (HDL)-Cholesterol
timeFrame: Baseline, Week 52
measure: Percentage Change from Baseline in Low Density Lipoprotein (LDL)-Cholesterol
timeFrame: Baseline, Week 52
measure: Percentage Change from Baseline in Very Low Density Lipoprotein (VLDL)-Cholesterol
timeFrame: Baseline, Week 52
measure: Percentage Change from Baseline in Non-HDL-Cholesterol
timeFrame: Baseline, Week 52
measure: Percentage Change from Baseline in Triglycerides
timeFrame: Baseline, Week 52
measure: Change from Baseline in Short Form 36 Version 2 (SF-36-v2) Acute Form Domain Summary Scores
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Absolute Clinical Research
state: Arizona
city: Canoga Park
country: United States
facility: San Fernando Valley Health Institute
state: California
city: Escondido
country: United States
facility: Neighborhood Healthcare Institute of Health
state: California
city: Gardena
country: United States
facility: Velocity Clinical Research, Gardena
state: California
city: Los Angeles
country: United States
facility: Biopharma Informatic, LLC
state: California
city: Los Angeles
country: United States
facility: Velocity Clinical Research, Westlake
state: California
city: Norco
country: United States
facility: Infinity Clinical Research - Norco
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: San Ramon
country: United States
facility: Norcal Endocrinology & Internal Medicine
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Tustin
country: United States
facility: University Clinical Investigators, Inc.
state: California
city: Golden
country: United States
facility: New West Physicians Clinical Research
state: Colorado
city: Cromwell
country: United States
facility: Connecticut Clinical Research - Cromwell
state: Connecticut
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc. (Clearwater)
state: Florida
city: Margate
country: United States
facility: South Florida Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research Institute, LLC
state: Florida
city: Ocoee
country: United States
facility: West Orange Endocrinology
state: Florida
city: Tamarac
country: United States
facility: Latin Clinical Trial Center Florida
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: West Palm Beach
country: United States
facility: Metabolic Research Institute, Inc.
state: Florida
city: Lawrenceville
country: United States
facility: Balanced Life Health Care Solutions/SKYCRNG
state: Georgia
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Woodstock
country: United States
facility: North Georgia Clinical Research
state: Georgia
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Idaho Falls
country: United States
facility: Family First Medical Center
state: Idaho
city: Greenfield
country: United States
facility: American Health Network of Indiana, LLC - Greenfield
state: Indiana
city: Valparaiso
country: United States
facility: Velocity Clinical Research, Valparaiso
state: Indiana
city: Topeka
country: United States
facility: Cotton O'Neil Diabetes & Endocrinology
state: Kansas
city: Wichita
country: United States
facility: Tekton Research, Inc
state: Kansas
city: New Orleans
country: United States
facility: DelRicht Research
state: Louisiana
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Dearborn
country: United States
facility: Revival Research Institute, LLC
state: Michigan
city: Ridgeland
country: United States
facility: SKY Integrative Medical Center/SKYCRNG
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Kalispell
country: United States
facility: Logan Health Research
state: Montana
city: Las Vegas
country: United States
facility: Wr-Crcn, Llc
state: Nevada
city: Trenton
country: United States
facility: Premier Research
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College, Division of Community Endocrinology
state: New York
city: Brooklyn
country: United States
facility: Ellipsis Research Group - Brooklyn - 7th Street
state: New York
city: Westfield
country: United States
facility: Great Lakes Medical Research, LLC
state: New York
city: Greensboro
country: United States
facility: PharmQuest Life Sciences, LLC
state: North Carolina
city: Morehead City
country: United States
facility: Lucas Research, Inc
state: North Carolina
city: Statesville
country: United States
facility: Accellacare - Piedmont
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center (WFUBMC)
state: North Carolina
city: Columbus
country: United States
facility: Aventiv Research Inc
state: Ohio
city: Moore
country: United States
facility: Tekton Research, Inc
state: Oklahoma
city: Norman
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Oklahoma
city: Corvallis
country: United States
facility: The Corvallis Clinic, P.C.
state: Oregon
city: Beaver
country: United States
facility: Heritage Valley Medical Group, Inc.
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Preferred Clinical Research (Ofc 18)
state: Pennsylvania
city: Greenville
country: United States
facility: The Research Center of The Upstate
state: South Carolina
city: Knoxville
country: United States
facility: New Phase Research and Development
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions Inc.
state: Tennessee
city: Austin
country: United States
facility: Velocity Clinical Research, Austin
state: Texas
city: Dallas
country: United States
facility: Velocity Clinical Research, Dallas
state: Texas
city: Fort Worth
country: United States
facility: Diabetes and Thyroid Center of Ft. Worth
state: Texas
city: Houston
country: United States
facility: Juno Research
state: Texas
city: Houston
country: United States
facility: Endocrine Ips, Pllc
state: Texas
city: Houston
country: United States
facility: Clear Brook Medical Associates
state: Texas
city: Mesquite
country: United States
facility: Southern Endocrinology Associates
state: Texas
city: Weslaco
country: United States
facility: Texas Valley Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: Synexus Clinical Research US, Inc.
state: Utah
city: Redmond
country: United States
facility: Eastside Research Associates
state: Washington
city: Renton
country: United States
facility: Rainier Clinical Research Center
state: Washington
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME)
state: Buenos Aires
city: Lanus
country: Argentina
facility: CIMeL
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Centro de Investigaciones Médicas Mar del Plata
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Policlinica Red OMIP
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: CIPREC
state: Ciudad Autónoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Centro Médico Viamonte
state: Ciudad Autónoma De Buenos Aires
city: Caba
country: Argentina
facility: Instituto Centenario
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: 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: Rosario
country: Argentina
facility: Instituto de Especialidades de la Salud Rosario
state: Santa Fe
city: Rosario
country: Argentina
facility: Instituto Médico Catamarca IMEC
state: Santa Fe
city: Rosario
country: Argentina
facility: Instituto Médico Fundación Grupo Colaborativo Rosario Investigación y Prevención Medica
state: Santa Fe
city: Rosario
country: Argentina
facility: Fundacion Estudios Clinicos
state: Santa Fe
city: Córdoba
country: Argentina
facility: Instituto de Investigaciones Clínicas Córdoba
city: Córdoba
country: Argentina
facility: Instituto Médico DAMIC
city: Santiago del Estero
country: Argentina
facility: Sanatorio Norte
city: Beijing
country: China
facility: Beijing Pinggu District Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing General Hospital
state: Chongqing
city: Foshan
country: China
facility: Shunde Hospital of Southern Medical Univesity
state: Guangdong
city: Huizhou
country: China
facility: Huizhou Municipal Central Hospital
state: Guangdong
city: Harbin
country: China
facility: The Fourth 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: Nanyang
country: China
facility: Nanyang First People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The Second Affiliated Hospital of Zhengzhou University
state: Henan
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
state: Jiangsu
city: Zhenjiang
country: China
facility: Affiliated Hospital of Jiangsu University
state: Jiangsu
city: Pingxiang
country: China
facility: Jiangxi Pingxiang People's Hospital
state: Jiangxi
city: Dalian
country: China
facility: Dalian Municipal Central Hospital Affiliated of Dalian Medical University
state: Liaoning
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Pudong New Area People's Hospital Shanghai
state: Shanghai
city: ChengDu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: Zhejiang Hospital
state: Zhejiang
city: Huzhou
country: China
facility: Huzhou Central Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Matsuyama
country: Japan
facility: Mikannohana Clinic, Diabetes, Endocrinology and Metabolism
state: Ehime
city: Sapporo
country: Japan
facility: Manda Memorial Hospital
state: Hokkaido
city: Mito
country: Japan
facility: Nakamoto Internal Medicine Clinic
state: Ibaraki
city: Naka
country: Japan
facility: Nakakinen clinic
state: Ibaraki
city: Tsuchiura
country: Japan
facility: Ohishi Internal Medicine Clinic
state: Ibaraki
city: Kamakura-shi
country: Japan
facility: Takai Internal Medicine Clinic
state: Kanagawa
city: Kashiwara
country: Japan
facility: Shiraiwa Medical Clinic
state: Osaka
city: Ootaku
country: Japan
facility: Medical Corporation Sato Medical clinic
state: Tokyo
city: Gifu
country: Japan
facility: Gifu University Hospital
city: Mexico City
country: Mexico
facility: Caimed Investigacion En Salud S.A. de C.V.
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: Centro de Investigacion Medica Integral
state: Jalisco
city: Guadalajara
country: Mexico
facility: Instituto Jalisciense de Investigacion en Diabetes y Obesidad
state: Jalisco
city: Guadalajara
country: Mexico
facility: CICEJ Centro de Investigación Clínica Endocrinológica de Jalisco S.C
state: Jalisco
city: Guadalajara
country: Mexico
facility: Private Practice - Dr. Arechavaleta Granell Maria del Rosario
state: Jalisco
city: Guadalajara
country: Mexico
facility: Virgen Cardiovascular Research SC
state: Jalisco
city: Zapopan
country: Mexico
facility: Centro de Investigacion Medica de Occidente, S.C.
state: Jalisco
city: Monterrey
country: Mexico
facility: Cardiolink Clin Trials
state: Nuevo León
city: Monterrey
country: Mexico
facility: Unidad biomedica avanzada monterrey
state: Nuevo León
city: Monterrey
country: Mexico
facility: Clínica García Flores SC
state: Nuevo León
city: Monterrey
country: Mexico
facility: Eukarya PharmaSite
state: Nuevo León
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo León
city: San Nicolás de los Garza
country: Mexico
facility: Centro de investigación y control metabólico
state: Nuevo León
city: Culiacan
country: Mexico
facility: Centro Para El Desarrollo de La Medicina Y de Asistencia Medica Especializada S.C.
state: Sinaloa
city: Durango
country: Mexico
facility: Lahoja. Asociacion Para La Investigacion Y La Farmacovigilancia
city: Guaynabo
country: Puerto Rico
facility: Isis Clinical Research Center
city: Ponce
country: Puerto Rico
facility: Research and Cardiovascular Corp.
city: San Juan
country: Puerto Rico
facility: Latin Clinical Trial Center
city: San Juan
country: Puerto Rico
facility: Mgcendo Llc
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: