Clinical trial NCT03495102: A Study of the Efficacy and Safety of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes
Official title: A Randomized, Double-Blind, Parallel Arm Study of the Efficacy and Safety of Investigational Dulaglutide Doses When Added to Metformin in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2018-04-11
Enrollment: 1842
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 investigational doses of once weekly dulaglutide when added to metformin in participants with type 2 diabetes with inadequate blood sugar control.


Eligibility criteria: Inclusion Criteria:

* Have type 2 diabetes mellitus (T2DM) for at least 6 months
* Have been treated with stable metformin dose for at least 3 months
* Have HbA1c ≥7.5% and ≤11.0% at study entry
* Have body mass index (BMI) ≥25 kilograms per meter squared (kg/m\^2)

Exclusion Criteria:

* Have type 1 diabetes mellitus
* Have used any glucagon-like peptide-1 receptor agonist (GLP-1 RA) or insulin, not including prior short term insulin use (≤14 days)
* Have been taking any other medicine for diabetes (other than metformin) during the last 3 months
* Have used in the last 3 months (or plan to use) prescription weight loss medications
* Have disorders associated with slowed emptying of the stomach contents, or have had any stomach surgeries for the purpose of weight loss
* Current participation in or intent to begin during the study an organized diet and/or exercise weight reduction program (other than the lifestyle and dietary measures for diabetes)
* Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine transaminase (ALT) level \>2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial
* Had chronic or acute pancreatitis any time prior to study entry
* Have had a heart attack or stroke in the past 2 months, or have heart failure that significantly limits their physical activity
* Estimated glomerular filtration rate (eGFR) \<30 milliliters/minute/1.73m\^2 (or lower than the country-specific threshold for discontinuing metformin therapy per local label), calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, as determined by the central laboratory at study entry and confirmed at lead-in
* Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2
* Have proliferative retinopathy or maculopathy requiring acute treatment according to the opinion of the investigator

Primary outcomes:
measure: Change in Hemoglobin A1c (HbA1c) From Baseline
timeFrame: Baseline, Week 36
Secondary outcomes:
measure: Change in Body Weight From Baseline
timeFrame: Baseline, Week 36
measure: Percentage of Participants Achieving HbA1c Target <7.0%
timeFrame: Week 36
measure: Change in Fasting Serum Glucose (FSG) From Baseline
timeFrame: Baseline, Week 36
measure: Rate of Documented Symptomatic Hypoglycemic Episodes
timeFrame: Week 36
measure: Pharmacokinetic (PK): Steady-state Maximum Concentration(Cmax,ss)
timeFrame: Week 4, Week 12, Week 36, Week 52
measure: Pharmacokinetic (PK): Area Under the Curve AUC (0-168)ss at Steady State
timeFrame: Week 4, Week 12, Week 36, Week 52
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Synexus- Chandler
state: Arizona
city: Mesa
country: United States
facility: Synexus/Central Arizona Medical Associates, PC
state: Arizona
city: Phoenix
country: United States
facility: Central Phoenix Med Clinic LLC
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Clinical Research
state: Arkansas
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: Montclair
country: United States
facility: Catalina Research Institute, LLC
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Oakland
country: United States
facility: Pacific Research Partners, LLC
state: California
city: Panorama City
country: United States
facility: National Research Institute
state: California
city: Roseville
country: United States
facility: Sierra Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Santa Clarita
country: United States
facility: Care Access Research
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: Walnut Creek
country: United States
facility: Diablo Clinical Research
state: California
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Cooper City
country: United States
facility: ALL Medical Research, LLC
state: Florida
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, LLC
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Oviedo
country: United States
facility: Oviedo Medical Research
state: Florida
city: Marietta
country: United States
facility: Urban Family Practice Associates, PC
state: Georgia
city: Peachtree Corners
country: United States
facility: In-Quest Medical Research, LLC- Peachtree Corners
state: Georgia
city: Honolulu
country: United States
facility: Pacific Diabetes & Endocrine Center
state: Hawaii
city: Honolulu
country: United States
facility: East West Medical Institute
state: Hawaii
city: Blackfoot
country: United States
facility: Elite Clinical Trials LLLP
state: Idaho
city: Nampa
country: United States
facility: Saltzer Medical Group. P.A.
state: Idaho
city: Springfield
country: United States
facility: Prairie Education and Research Cooperative
state: Illinois
city: Evansville
country: United States
facility: Synexus/Clinical Research Advantage
state: Indiana
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: West Des Moines
country: United States
facility: Iderc, P.L.C.
state: Iowa
city: Portland
country: United States
facility: InterMed, PA
state: Maine
city: Hyattsville
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Fall River
country: United States
facility: NECCR PrimaCare Research, LLC
state: Massachusetts
city: Flint
country: United States
facility: Aa Mrc Llc
state: Michigan
city: Troy
country: United States
facility: Troy Internal Medicine, PC
state: Michigan
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Saint Peters
country: United States
facility: StudyMetrix Research, LLC
state: Missouri
city: Billings
country: United States
facility: Montana Health Research
state: Montana
city: Kalispell
country: United States
facility: Glacier View Research Institute
state: Montana
city: Trenton
country: United States
facility: Premier Research
state: New Jersey
city: New York
country: United States
facility: Manhattan Medical Research
state: New York
city: Westfield
country: United States
facility: Great Lakes Medical Research
state: New York
city: Charlotte
country: United States
facility: Metrolina Internal Medicine, P.A.
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes & Endocrinology Consultants PC
state: North Carolina
city: Columbus
country: United States
facility: Aventiv Research
state: Ohio
city: Norman
country: United States
facility: Intend Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Corvallis
country: United States
facility: The Corvallis Clinic P.C.
state: Oregon
city: Portland
country: United States
facility: Summit Research Network Inc
state: Oregon
city: Beaver
country: United States
facility: Heritage Valley Medical Group, Inc.
state: Pennsylvania
city: Lansdale
country: United States
facility: Detweiler Family Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians
state: Pennsylvania
city: Warwick
country: United States
facility: Sudir Bansal M.D. Inc.
state: Rhode Island
city: Moncks Corner
country: United States
facility: PMG Research of Charleston, LLC
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Research and Medicine (CHARM)
state: Tennessee
city: Dallas
country: United States
facility: Dallas Diabetes Endocrine Center
state: Texas
city: Mesquite
country: United States
facility: Southern Endocrinology and Associates PA
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research
state: Texas
city: Tomball
country: United States
facility: Martin Diagnostic Clinic
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials, LLC
state: Texas
city: Bountiful
country: United States
facility: Progressive Clinical Research
state: Utah
city: Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Manassas
country: United States
facility: Manassas Clinical Research Center
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners, LLC
state: Virginia
city: Olympia
country: United States
facility: Capital Clincial Research Center
state: Washington
city: Walla Walla
country: United States
facility: Walla Walla Clinic
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital & Clinics
state: Washington
city: Green Bay
country: United States
facility: Prevea Clinic, Inc
state: Wisconsin
city: Caba
country: Argentina
facility: Centro Medico CICEMO
state: Buenos Aires
city: Caba
country: Argentina
facility: CEDIC-Centro de Investigaciones Clinicas
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigaciones Medicas IMOBA S.R.L.
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME)
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Centro Medico Dr Laura Maffei Investigacion Clinica Aplicada
state: Buenos Aires
city: Ciudad Autonoma de
country: Argentina
facility: Centro de Investigacion y Prevencion Cardiovascular (CIPREC)
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas Mar del Plata
state: Buenos Aires
city: Godoy Cruz
country: Argentina
facility: CIPADI
state: Mendoza
city: Buenos Aires
country: Argentina
facility: AXISMED SRL - Bioclinica Research Network
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: CENUDIAB
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Centro Médico Viamonte
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Instituto Centenario
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Cemediab - Centro Médico Diabetológico Dr. Alejandro Chertkoff
city: Ciudad Autonoma De Buenos Air
country: Argentina
facility: Mautalen Salud e Investigación - Servicio de Endocrinología
city: Cordoba
country: Argentina
facility: Instituto Medico Strusberg
city: Cordoba
country: Argentina
facility: Centro Medico Privado San Vicente Diabetes
city: Cordoba
country: Argentina
facility: Cent Priva Especiali Médicas Ambulatorias Inve Clin CEMAIC
city: Stockerau
country: Austria
facility: Landesklinikum Korneuburg-Stockerau, Standort Stockerau
state: Niederösterreich
city: Graz
country: Austria
facility: Universitätsklinikum Graz
state: Steiermark
city: Saint Stefan Ob Stainz
country: Austria
facility: Ordination Dr. Evelyn Fließer-Görzer
state: Steiermark
city: Feldkirch
country: Austria
facility: VIVIT Institut am LKH Feldkirch
state: Vorarlberg
city: Wien
country: Austria
facility: KA Rudolfstiftung
city: Wien
country: Austria
facility: Zentrum für klinische Studien Dr. Ursula Hanusch GmbH
city: Red Deer
country: Canada
facility: Bailey Clinic
state: Alberta
city: Brampton
country: Canada
facility: Aggarwal and Associates Ltd
state: Ontario
city: Mississauga
country: Canada
facility: T. Nemtean Medicine Professional Corporation
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc
state: Ontario
city: Stayner
country: Canada
facility: Stayner Medical Clinic
state: Ontario
city: Toronto
country: Canada
facility: Dr. Anil K. Gupta Medicine Professional Corporation
state: Ontario
city: Palaio Faliro
country: Greece
facility: Iatriko Palaiou Falirou, Medical Center
state: Athens
city: Ampelokipoi
country: Greece
facility: Laiko General Hospital of Athens
state: Attica
city: Athens
country: Greece
facility: Gen Hospital of Athens G Gennimatas
state: Attiki
city: Exohi
country: Greece
facility: G.Papanikolaou General Hospital
state: Thessaloniki
city: Thermi
country: Greece
facility: Thermi Clinic
state: Thessaloniki
city: Athens
country: Greece
facility: Athens Euroclinic
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloniki
country: Greece
facility: AHEPA Hospital
city: Thessaloniki
country: Greece
facility: Ippokrateio General Hospital of Thessaloniki
city: Thessaloniki
country: Greece
facility: Euromedica - General Clinic of Thessaloniki
city: Kalocsa
country: Hungary
facility: Studium Egeszseghaz Kft.
state: Bacs-Kiskun
city: Debrecen
country: Hungary
facility: Kenezy Gyula Korhaz es Rendelointezet
state: Hajdu-Bihar
city: Papa
country: Hungary
facility: Grof Esterhazy Korhaz es Rendelointezeti Szakrendelo
state: Veszprem
city: Budapest
country: Hungary
facility: Szent Margit Rendelointezet
city: Budapest
country: Hungary
facility: ClinDiab Kft.
city: Budapest
country: Hungary
facility: Strazsahegy Medicina Bt.
city: Budapest
country: Hungary
facility: TRANTOR 99 Bt.
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Korhaz
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Korhaz
city: Haifa
country: Israel
facility: Maccabi Diabetes Clinic, Grand Canyon, North District, Haifa
city: Haifa
country: Israel
facility: Linn Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Raanana
country: Israel
facility: Clalit Health Services - Shuali Clinic
city: Safed
country: Israel
facility: ZIV Medical Center
city: Sakhnin
country: Israel
facility: Sakhnin Community Clinic, Clalit Health Services
city: Tel Aviv Jaffa
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Diabetes Medical Center (DMC)
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Florence
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Siena
country: Italy
facility: A.O.U. Senese Policlinico Santa Maria alle Scotte
state: SI
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Catanzaro
country: Italy
facility: Policlinico Mater Domini
city: Chieti
country: Italy
facility: Fondazione Universitaria degli Studi G D'Annunzio
city: Latina
country: Italy
facility: Ospedale Santa Maria Goretti
city: Palermo
country: Italy
facility: Policlinico Giaccone
city: Verona
country: Italy
facility: Ospedale Civile Maggiore Borgo Trento
city: Monterrey
country: Mexico
facility: Hospital Univ. Dr. Jose Eleuterio Gonzalez
state: Nuevo León
city: Chihuahua
country: Mexico
facility: Investigacion en Salud y Metabolismo S.C
city: Bialystok
country: Poland
facility: NZOZ ZDROWIE Osteo-Medic
city: Bialystok
country: Poland
facility: Poradnia Diabetologiczna SN ZOZ Lege Artis
city: Bialystok
country: Poland
facility: NS ZOZ Osrodek Diabetologiczny " Popula"
city: Gdansk
country: Poland
facility: Centrum Badan Klinicznych, PI House
city: Katowice
country: Poland
facility: NZOZ Salvia s.c.
city: Krakow
country: Poland
facility: NZOZ Diab-Endo-Met
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.
city: Lublin
country: Poland
facility: Gabinety Terpa
city: Lublin
country: Poland
facility: NZOZ Przychodnia Specjalistyczna MEDICA
city: Poznan
country: Poland
facility: Centrum Medyczne OMEDICA
city: Poznan
country: Poland
facility: Praktyka Lekarska
city: Poznan
country: Poland
facility: Nzoz Neuro - Kard
city: Ruda Slaska
country: Poland
facility: NZOZ Przychodnia Specjalistyczna Henryk RudzkiAndrzej Wittek
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSW
city: Wroclaw
country: Poland
facility: Regionalna Poradnia Diabetologiczna
city: Ponce
country: Puerto Rico
facility: Research and Cardiovascular Corp.
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico, Inc.
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC
city: San Juan
country: Puerto Rico
facility: Office: Dr. Luis Rivera Colon
city: Oradea
country: Romania
facility: S. C. Grandmed S.R.L., Str.
state: Bihor
city: Mangalia
country: Romania
facility: SC Gama Diamed SRL
state: Constanta
city: Satu-Mare
country: Romania
facility: Spitalul Judetean de Urgenta Satu Mare
state: Jud Satu-Mare
city: Baia Mare
country: Romania
facility: CMI DNBM Dr. Pop Lavinia
state: Maramures
city: Targu Mures
country: Romania
facility: Cosamext SRL
state: Mures
city: Ploiesti
country: Romania
facility: SC Diabmed Dr Popescu Alexandrina SRL
state: Prahova
city: Ploiesti
country: Romania
facility: SC Dianutrilife Medica SRL
state: Prahova
city: Timisoara
country: Romania
facility: Centrul Medical Dr. Negrisanu
state: Timis
city: Brasov
country: Romania
facility: Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed SRL
city: Bucharest
country: Romania
facility: Cabinetul Medical Nicodiab SRL
city: Bucuresti
country: Romania
facility: Easydiet SRL
city: Bucuresti
country: Romania
facility: SC Nutrilife SRL
city: Buzau
country: Romania
facility: SC Medcon SRL
city: Cluj Napoca
country: Romania
facility: Centrul Medical Unirea SRL
city: Craiova
country: Romania
facility: Cabinet Medical Urodiamed S.R.L.
city: Galati
country: Romania
facility: Milena Sante SRL
city: Iasi
country: Romania
facility: SC Olimpia Med SRL
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Hospital
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk the first city clinical hospital
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University
city: Saint Petersburg
country: Russian Federation
facility: City Hospital of Saint Martyr Elizabeth
city: Saint Petersburg
country: Russian Federation
facility: SPb GUZ "Diagnostic Center #85"
city: Saratov
country: Russian Federation
facility: Regional Clinical Hospital
city: Kosice
country: Slovakia
facility: Human care s.r.o.
state: Slovak Republic
city: Malacky
country: Slovakia
facility: MediVet s.r.o.
state: Slovak Republic
city: Trebisov
country: Slovakia
facility: Areteus s.r.o.
state: Slovak Republic
city: Bratislava
country: Slovakia
facility: Diacrin s.r.o.
city: Nove Mesto nad Vahom
country: Slovakia
facility: Noemis, s.r.o.
city: Nove Zamky
country: Slovakia
facility: FUNKYSTUFF s.r.o.
city: Prievidza
country: Slovakia
facility: MUDr. Jan Culak, s.r.o.
city: Puchov
country: Slovakia
facility: DIA-MED CENTRUM s.r.o.
city: Roznava
country: Slovakia
facility: Tatratrial s.r.o.
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa
state: Andalucía
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Tauli
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques De Valdecilla
state: Cantabria
city: Palma de Mallorca
country: Spain
facility: Clinica Juaneda
state: Islas Baleares
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Madrid
state: Madrid
city: Alicante
country: Spain
facility: Instituto de Ciencias medicas
city: Almeria
country: Spain
facility: Clinica San Pedro
city: Barcelona
country: Spain
facility: Centre Medico Teknon
city: Granada
country: Spain
facility: Hospital Clinico Universitario San Cecilio
city: Granada
country: Spain
facility: Virgen de Las Nieves
city: Malaga
country: Spain
facility: Centro Especialidades San Jose Obrero (Barbarela)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Seville
country: Spain
facility: Clinica Nuevas Tecnologias en Diabetes y Endocrinologia
city: Teruel
country: Spain
facility: Policlinica Galileo
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan City
country: Taiwan
facility: Chi-Mei Medical Center
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:
citation: Cox DA, Wang H, Nicolay C, Bethel MA. Effect of expanded dulaglutide weekly doses (3.0 mg and 4.5 mg) on cardiovascular disease risk factors in participants with type 2 diabetes at increased cardiovascular disease risk: a post hoc analysis of the AWARD-11 study. Diabetes Obes Metab. 2022 Sep;24(9):1770-1778. doi: 10.1111/dom.14762. Epub 2022 May 29.
citation: Frias JP, Bonora E, Nevarez Ruiz L, Li YG, Yu Z, Milicevic Z, Malik R, Bethel MA, Cox DA. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11). Diabetes Care. 2021 Mar;44(3):765-773. doi: 10.2337/dc20-1473. Epub 2021 Jan 4.