Empagliflozin as Adjunctive to Insulin Therapy Over 26 Weeks in Patients With T1DM (EASE-3)

NCT ID: NCT02580591

Last Updated: 2018-11-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 977 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-22
• Study Completion Date: 2017-09-20

Brief Summary

The study will investigate the efficacy, safety, tolerability and Pharmacokinetic(PK) of 3 doses of empagliflozin compared with placebo over 26 weeks in 960 patients with type 1 diabetes mellitus as adjunctive therapy to insulin

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Empagliflozin low dose

Group Type: EXPERIMENTAL

Empagliflozin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

For blinding purposes

Empagliflozin high dose

Group Type: EXPERIMENTAL

Empagliflozin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

For blinding purposes

Empagliflozin medium dose

Group Type: EXPERIMENTAL

Empagliflozin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

For blinding purposes

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

For blinding purposes

Interventions

Empagliflozin

Intervention Type: DRUG

Placebo

For blinding purposes

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed and dated written informed consent
• Male or female patient receiving insulin for the treatment of documented diagnosis of type 1 diabetes mellitus (T1DM) > 1 year
• C-peptide value of < 0.7 ng/mL
• Use of Multiple Daily Injections (MDI) of insulin or insulin pump user with total daily insulin >= 0.3 and <= 1.5 U/kg
• Glycated haemoglobin (HbA1c) >= 7.5% and <= 10.0%
• Good understanding of T1DM
• Age >= 18 years
• Body Mass Index (BMI) >= 18.5 kg/m2
• Estimated glomerular filtration rate >= 30 mL/min/1.73 m2
• Women of child-bearing potential must use highly effective methods of birth control

Exclusion Criteria

• History of type 2 diabetes mellitus, maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis
• Pancreas, pancreatic islet cells or renal transplant recipient
• T1DM treatment with any other antihyperglycaemic drug except subcutaneous basal and bolus insulin within last 3 months
• Occurrence of severe hypoglycaemia within last 3 months and until randomisation
• Occurence of diabetic ketoacidosis within 3 months prior to Visit 1 and until Visit 6
• Irregular sleep/wake cycle
• Acute coronary syndrome, stroke or Transient Ischaemic Attack (TIA) within last 3 months
• Severe gastroparesis
• Brittle diabetes
• Liver disease
• Eating disorders
• Treatment with anti-obesity drugs, weight-loss surgery or aggressive diet regimen
• Treatment with systemic corticosteroids
• Change in dose of thyroid hormones within last 6 weeks and until randomisation
• Cancer or treatment for cancer in the last five years
• Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells
• Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial
• Alcohol or drug abuse

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Healthscan Clinical Trials LLC

Montgomery, Alabama, United States

John Muir Physician Network Clinical Research Center

Concord, California, United States

Valley Research

Fresno, California, United States

Marin Endocrine Care and Research

Greenbrae, California, United States

Pacific Research Partners, LLC

Oakland, California, United States

NorCal Endocrinology and Internal Medicine

San Ramon, California, United States

William Sansum Diabetes Center

Santa Barbara, California, United States

University of Colorado Denver

Aurora, Colorado, United States

International Research Associates, LLC

Hialeah, Florida, United States

Solutions Through Advanced Research, Inc.

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

Suncoast Clinical Research, Inc.

New Port Richey, Florida, United States

Atlanta Diabetes Associates

Atlanta, Georgia, United States

Physicians Research Associates, LLC

Lawrenceville, Georgia, United States

Sestron Clinical Research

Marietta, Georgia, United States

Eagle's Landing Diabetes and Endocrinology

Stockbridge, Georgia, United States

Northwest Endo Diabetes Research, LLC

Arlington Heights, Illinois, United States

Kentucky Diabetes Endocrinology Center

Lexington, Kentucky, United States

University of Maryland School of Medicine

Baltimore, Maryland, United States

MODEL Clinical Research

Baltimore, Maryland, United States

Clinical Research Consultants, LLC

Kansas City, Missouri, United States

Desert Endocrinology Clinical Research Center

Henderson, Nevada, United States

Palm Research Center

Las Vegas, Nevada, United States

Endocrine-Diabetes Care and Resource Center

Rochester, New York, United States

Endocrine Associates of Long Island, PC

Smithtown, New York, United States

Diabetes Endocrinology Research Center of Western New York

Williamsville, New York, United States

Diabetes and Endocrinology Consultants, PC

Morehead City, North Carolina, United States

Holzer Clinic LLC

Gallipolis, Ohio, United States

COR Clinical Research, LLC

Oklahoma City, Oklahoma, United States

Strand Physician Specialists dba Carolina Health Specialists

Myrtle Beach, South Carolina, United States

AM Diabetes and Endocrinology Center

Bartlett, Tennessee, United States

Holston Medical Group

Bristol, Tennessee, United States

University Diabetes and Endocrine Consultants

Chattanooga, Tennessee, United States

Texas Diabetes & Endocrinology PA

Austin, Texas, United States

Texas Health Physicians Group

Dallas, Texas, United States

Dallas Diabetes and Endocrine Center

Dallas, Texas, United States

Research Institute of Dallas

Dallas, Texas, United States

Endeavor Clinical Trials, PA

San Antonio, Texas, United States

Virginia Endocrinology Research

Chesapeake, Virginia, United States

Coffs Endocrine & Diabetes Services

Coffs Harbour, New South Wales, Australia

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

SA Endocrine Research P/L

Keswick, South Australia, Australia

Eastern Clinical Research Unit

East Ringwood, Victoria, Australia

Richmond Road and Diagnostic Treatment Centre

Calgary, Alberta, Canada

The Bailey Clinic

Red Deer, Alberta, Canada

Eastern Health (MUN)

St. John's, Newfoundland and Labrador, Canada

Centre for Studies in Family Medicine

London, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Omnispec Recherche Clinique Inc.

Mirabel, Quebec, Canada

Applied Medical Informatics Research INC.

Westmount, Quebec, Canada

Clinique des maladies Lipidiques de Quebec

Québec, , Canada

University Hospital Brno

Brno, , Czechia

Diahaza s.r.o.Intern.Med.Outpat.Clin.Dep.Diabetology,Holesov

Holešov, , Czechia

AIDIN VK s.r.o.,Department Diabetology, Hranice

Hranice, , Czechia

Univ. Hospital Kralovske Vinohrady

Prague, , Czechia

DiaGolfova s.r.o., Department Diabetology, Prague

Prague, , Czechia

Milan Kvapil s.r.o.,Diabetology ambulance,Prague

Prague, , Czechia

ResTrial s.r.o.Diabetology Ambulance,Prague

Prague, , Czechia

HUS, Lihavuustutkimusyksikkö Biomedicum Helsinki

Helsinki, , Finland

Mehiläinen Jyväskylä

Jyväskylä, , Finland

Satakunnan Diabetesasema, Pori

Pori, , Finland

FinnMedi Oy, Tampere

Tampere, , Finland

TYKS

Turku, , Finland

HOP Jean Minjoz

Besançon, , France

HOP Le Creusot

Le Creusot, , France

HOP Paris Saint-Joseph

Paris, , France

HOP Bichat

Paris, , France

HOP de Poitiers

Poitiers, , France

HOP Civil

Strasbourg, , France

HOP Rangueil

Toulouse Cédex 04, , France

Diabetes-Klinik Bad Mergentheim GmbH & Co. KG

Bad Mergentheim, , Germany

Diabetologische Schwerpunktpraxis, Bosenheim

Bosenheim, , Germany

Praxis Dr. Busch, Dortmund

Dortmund, , Germany

GWT-TUD GmbH

Dresden, , Germany

ZKS Südbrandenburg GmbH

Elsterwerda, , Germany

InnoDiab Forschung GmbH

Essen, , Germany

Praxis Dr. Kaiser, Frankfurt

Frankfurt, , Germany

Institut für Diabetesforschung Münster GmbH

Münster, , Germany

Diabetologische Schwerpunktpraxis

Münster, , Germany

Praxis Dr. Behnke, Neuwied

Neuwied, , Germany

Praxis Dr. Hilgenberg

Rehburg-Loccum, , Germany

"Korgialeneio-Benakeio" Hellenic Red Cross Hospital

Athens, , Greece

General Hospital of Athens "Laiko"

Athens, , Greece

Univ. Gen. Hosp. of Ioannina

Ioannina, , Greece

General Hospital of Nikaia

Nikaia, , Greece

General Hopsital of Thessaloniki "Ippokrateio"

Thessaloniki, , Greece

General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, , Greece

Clinexpert Kft.

Budapest, , Hungary

Synexus Magyarorszag Kft.

Budapest, , Hungary

University Debrecen Hospital

Debrecen, , Hungary

CRU Hungary Ltd, Private Practice, Miskolc

Miskolc, , Hungary

Clinfan SMO Ltd.

Szekszárd, , Hungary

Csongrad Country Dr Bugyi Istvan Hosp.

Szentes, , Hungary

Zala Country Hospital, Diabetic Outpatient Clinic

Zalaegerszeg, , Hungary

Mater Misericordiae University Hospital

Dublin, , Ireland

Inrca-Irccs

Ancona, , Italy

A.O. Spedali Civili di Brescia

Brescia, , Italy

Osp. Campo di Marte

Lucca, , Italy

Azienda Ospedaliera Universitaria "Federico II"

Napoli, , Italy

Policlinico Gemelli

Roma, , Italy

Osp. S. Giovanni Calibita Fatebenefratelli

Roma, , Italy

IRCCS Gruppo Multimedica

Sesto San Giovanni (MI), , Italy

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, , Italy

Ospedale Molinette, AO Città della Salute e della

Torino, , Italy

Zemgales Center of diabetes, Jelgava

Jelgava, , Latvia

A. Lucenko's Internist & Endocrinologist Doctor's Practice

Liepāja, , Latvia

Dace Teterovska Doctor's Practice in Endocrinology,Ogre

Ogre, , Latvia

P. Stradins Clinical University Hospital, Riga

Riga, , Latvia

Riga Health Center, Private Practice

Riga, , Latvia

Sigulda Hospital, Outpatient department

Sigulda, , Latvia

VSV Centrs, Stalte Private Practice, Talsi

Talsi, , Latvia

Clínica EndocrInol en Diabetes Obesidad y Tiroides (DOT)

Aguascalientes, , Mexico

Hospital Cardiologica Aguascalientes

Aguascalientes, , Mexico

Unidad de Investigacion Clinica Cardiometabolica de Occident

Guadalajara, , Mexico

Instituto Jaliscience de Inv. en Diabetes y Obesidad, S.C.

Guadalajara, , Mexico

Unidad de Patologia Clinica

Guadalajara, , Mexico

Noordwest Ziekenhuisgroep

Alkmaar, , Netherlands

Ziekenhuisgroep Twente locatie Almelo

Almelo, , Netherlands

Meander Medisch Centrum

Amersfoort, , Netherlands

Gelre Ziekenhuizen Apeldoorn

Apeldoorn, , Netherlands

EB Utrecht Research

Utrecht, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

South Pacific Clinical Trials

Auckland, New Zealand, , New Zealand

Lipid and Diabetes Research Group

Christchurch, , New Zealand

M3 Helse AS

Hamar, , Norway

Oslo Universitetssykehus HF, Lipidklinikken

Oslo, , Norway

Stavanger Helseforskning

Stavanger, , Norway

Universitetssykehuset Nord-Norge, Tromsø

Tromsø, , Norway

DiabSerwis S.C., Chorzow

Chorzów, , Poland

Medical Centre Pratia Gdynia

Gdynia, , Poland

Medical Centre Pratia Katowice I

Katowice, , Poland

Medical Centre Pratia Krakow

Krakow, , Poland

University Hospital in Krakow

Krakow, , Poland

Independent Public Clin.Hosp.no1Lublin,Dep.Internal Diseases

Lublin, , Poland

Witold Chodzko Institute Rural Medic,Dep.Diabetology,Lublin

Lublin, , Poland

Reg.Spec.Hosp.Olsztyn,Clin,Endocrinology,Diabetics.&Int.Med.

Olsztyn, , Poland

Clinical Research Center Medicome, Oswiecim

Oświęcim, , Poland

Omedica Medical Centre, Poznan

Poznan, , Poland

Medical Centre Pratia Warszawa

Warsaw, , Poland

NZOZ Med-Art.Specialist Clinics, Zory

Żory, , Poland

Hospital de Braga-Escala Braga

Braga, , Portugal

Centro Hospitalar da Cova da Beira Hospital Pêro da Covilhã

Covilha, , Portugal

APDP - Associação Protectora dos Diabéticos de Portugal

Lisbon, , Portugal

H. Santo António - Centro Hospitalar do Porto

Porto, , Portugal

Centro Hospitalar São João,EPE

Porto, , Portugal

ULSAM, EPE - Hospital de Santa Luzia

Viana do Castelo, , Portugal

Centro Hospitalar de Vila Nova de Gaia

Vila Nova de Gaia, , Portugal

Nicodiab SRL, Bucharest

Bucharest, , Romania

Milit. Cent. Emerg. Univ. Hosp. Dr. Davila, Met. Dis. Dept.

Bucharest, , Romania

SC Medical Centre "Sanatatea Ta" SRL, Bucharest

Bucharest, , Romania

SC Pelican Impex SRL, Cabinet Nr. 201, Diabetes Dept.

Oradea, Bihor County, , Romania

Centrul Medical Dr Negrisanu SRL

Timișoara, , Romania

City Clinical Hospital no. 67, Moscow

Moscow, , Russia

CJSC"Polyclinic complex",Dep.Endocrinology,St.Petersburg

Saint Petersburg, , Russia

City Outpatient dep.no.107;clinc.pharmacology,st.petersburg

Saint Petersburg, , Russia

Medical Academy named after I. Mechnikov, St. Petersburg

Saint Petersburg, , Russia

City Hospital Saint Elizaveta, Dept. Endocrinology

Saint Petersburg, , Russia

Policlinic No. 1 of Russian Academy of Sciences, St. Petersburg

Saint Petersburg, , Russia

LCS Clinical Research Unit

Bryanston, , South Africa

TREAD Research

Cape Town, , South Africa

Dr Hilton Kaplan

Cape Town, , South Africa

Dr. L. A.Distiller

Johannesburg, , South Africa

VX Pharma (Pty) Ltd Pretoria

Pretoria, , South Africa

Diabetes Care Centre

Pretoria, , South Africa

Hospital A Coruña

A Coruña, , Spain

CM Avances Médicos

Granada, , Spain

Hospital de la Inmaculada Concepción

Granada, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario Infanta Leonor

Madrid, , Spain

Endo-Diabesidad-Clínica Durán & Asociados

Seville, , Spain

Hospital Virgen Macarena

Seville, , Spain

Hospital Clínico de Valencia

Valencia, , Spain

Ängelholms Sjukhus

Ängelholm, , Sweden

CTC Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Karlskoga lasarett

Karlskoga, , Sweden

Skånes universitetssjukhus, Lund

Lund, , Sweden

S3 Clinical Research Centers

Vällingby, , Sweden

Royal Bournemouth and Christchurch Hospital

Bournemouth, , United Kingdom

Bradford Royal Infirmary

Bradford, , United Kingdom

Hull Royal Infirmary

Hull, , United Kingdom

Ipswich Hospital

Ipswich, , United Kingdom

Leicester General Hospital

Leicester, , United Kingdom

Guy's Hospital

London, , United Kingdom

King's College Hospital

London, , United Kingdom

St Mary's Hospital

London, , United Kingdom

James Cook University Hospital

Middlesbrough, , United Kingdom

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Queen's Medical Centre

Nottingham, , United Kingdom

George Eliot Hospital

Nuneaton, , United Kingdom

Countries

United States; Australia; Canada; Czechia; Finland; France; Germany; Greece; Hungary; Ireland; Italy; Latvia; Mexico; Netherlands; New Zealand; Norway; Poland; Portugal; Romania; Russia; South Africa; Spain; Sweden; United Kingdom

References

Song C, Dhaliwal S, Bapat P, Scarr D, Bakhsh A, Budhram D, Verhoeff NJ, Weisman A, Fralick M, Ivers NM, Cherney DZI, Tomlinson G, Lovblom LE, Mumford D, Perkins BA. Point-of-Care Capillary Blood Ketone Measurements and the Prediction of Future Ketoacidosis Risk in Type 1 Diabetes. Diabetes Care. 2023 Nov 1;46(11):1973-1977. doi: 10.2337/dc23-0840.

Reference Type: DERIVED

PMID: 37616393 (View on PubMed)

Rosenstock J, Marquard J, Laffel LM, Neubacher D, Kaspers S, Cherney DZ, Zinman B, Skyler JS, George J, Soleymanlou N, Perkins BA. Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials. Diabetes Care. 2018 Dec;41(12):2560-2569. doi: 10.2337/dc18-1749. Epub 2018 Oct 4.

Reference Type: DERIVED

PMID: 30287422 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-005256-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1245.72

Identifier Type: -

Identifier Source: org_study_id