Empagliflozin as Adjunctive to Insulin Therapy Over 26 Weeks in Patients With T1DM (EASE-3)
A Phase III, Randomised, Double Blind, Placebo-controlled, Parallel Group, Efficacy, Safety and Tolerability Trial of Once Daily, Oral Doses of Empagliflozin as Adjunctive to Insulin Therapy Over 26 Weeks in Patients With Type 1 Diabetes Mellitus (EASE-3)
2 other identifiers
interventional
977
24 countries
189
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2015
189 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 19, 2015
CompletedFirst Posted
Study publicly available on registry
October 20, 2015
CompletedStudy Start
First participant enrolled
December 22, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 12, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
September 20, 2017
CompletedResults Posted
Study results publicly available
November 2, 2018
CompletedNovember 2, 2018
October 1, 2018
1.7 years
October 19, 2015
September 20, 2018
October 31, 2018
Conditions
Outcome Measures
Primary Outcomes (2)
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 for Full Analysis Set (FAS) (Observed Cases [OC])
Change from baseline in Glycated hemoglobin (HbA1c) for full analysis set (FAS) (observed cases \[OC\]) is presented. With regards to efficacy and safety endpoints, the term 'baseline' referred to the last observed measurement prior to administration of any randomized trial medication. Least squares mean is adjusted mean change from baseline.
Baseline to week 26
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 for Modified Intention-to-treat Population Set (mITT) (Observed Case (OC) - All Data (AD) (OC-AD))
Change from baseline in Glycated hemoglobin (HbA1c) for modified intention-to-treat population set (mITT) (observed case - all data \[OC-AD\]) is presented. With regards to efficacy and safety endpoints, the term 'baseline' referred to the last observed measurement prior to administration of any randomized trial medication. Least squares mean is adjusted mean change from baseline.
Baseline to week 26
Secondary Outcomes (4)
Rate Per Patient-year of Investigator-reported Symptomatic Hypoglycemic Adverse Events (AEs) With Confirmed Plasma Glucose (PG)
Week 5 to Week 26, Week 1 to Week 26
Change From Baseline in Body Weight at Week 26
Baseline to week 26
Change From Baseline in Total Daily Insulin Dose (TDID) at Week 26
Baseline to week 26
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 26
Baseline to week 26
Study Arms (4)
Empagliflozin low dose
EXPERIMENTALEmpagliflozin high dose
EXPERIMENTALEmpagliflozin medium dose
EXPERIMENTALPlacebo
PLACEBO COMPARATORInterventions
For blinding purposes
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Boehringer Ingelheimlead
- Eli Lilly and Companycollaborator
Study Sites (189)
Healthscan Clinical Trials LLC
Montgomery, Alabama, 36106, United States
John Muir Physician Network Clinical Research Center
Concord, California, 94520, United States
Valley Research
Fresno, California, 93720, United States
Marin Endocrine Care and Research
Greenbrae, California, 94904, United States
Pacific Research Partners, LLC
Oakland, California, 94607, United States
NorCal Endocrinology and Internal Medicine
San Ramon, California, 94583, United States
William Sansum Diabetes Center
Santa Barbara, California, 93105, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
International Research Associates, LLC
Hialeah, Florida, 33012, United States
Solutions Through Advanced Research, Inc.
Jacksonville, Florida, 32225, United States
University of Miami
Miami, Florida, 33136, United States
Suncoast Clinical Research, Inc.
New Port Richey, Florida, 34652, United States
Atlanta Diabetes Associates
Atlanta, Georgia, 30318, United States
Physicians Research Associates, LLC
Lawrenceville, Georgia, 30046, United States
Sestron Clinical Research
Marietta, Georgia, 30060, United States
Eagle's Landing Diabetes and Endocrinology
Stockbridge, Georgia, 30281, United States
Northwest Endo Diabetes Research, LLC
Arlington Heights, Illinois, 60005, United States
Kentucky Diabetes Endocrinology Center
Lexington, Kentucky, 40503, United States
University of Maryland School of Medicine
Baltimore, Maryland, 21201, United States
MODEL Clinical Research
Baltimore, Maryland, 21204, United States
Clinical Research Consultants, LLC
Kansas City, Missouri, 64111, United States
Desert Endocrinology Clinical Research Center
Henderson, Nevada, 89052, United States
Palm Research Center
Las Vegas, Nevada, 89128, United States
Endocrine-Diabetes Care and Resource Center
Rochester, New York, 14607, United States
Endocrine Associates of Long Island, PC
Smithtown, New York, 11787, United States
Diabetes Endocrinology Research Center of Western New York
Williamsville, New York, 14221, United States
Diabetes and Endocrinology Consultants, PC
Morehead City, North Carolina, 28557, United States
Holzer Clinic LLC
Gallipolis, Ohio, 45631, United States
COR Clinical Research, LLC
Oklahoma City, Oklahoma, 73103, United States
Strand Physician Specialists dba Carolina Health Specialists
Myrtle Beach, South Carolina, 29572, United States
AM Diabetes and Endocrinology Center
Bartlett, Tennessee, 38133, United States
Holston Medical Group
Bristol, Tennessee, 37620, United States
University Diabetes and Endocrine Consultants
Chattanooga, Tennessee, 37411, United States
Texas Diabetes & Endocrinology PA
Austin, Texas, 78749, United States
Texas Health Physicians Group
Dallas, Texas, 75218, United States
Dallas Diabetes and Endocrine Center
Dallas, Texas, 75230, United States
Research Institute of Dallas
Dallas, Texas, 75231, United States
Endeavor Clinical Trials, PA
San Antonio, Texas, 78229, United States
Virginia Endocrinology Research
Chesapeake, Virginia, 23321, United States
Coffs Endocrine & Diabetes Services
Coffs Harbour, New South Wales, 2450, Australia
Lyell McEwin Hospital
Elizabeth Vale, South Australia, 5112, Australia
SA Endocrine Research P/L
Keswick, South Australia, 5035, Australia
Eastern Clinical Research Unit
East Ringwood, Victoria, 3135, Australia
Richmond Road and Diagnostic Treatment Centre
Calgary, Alberta, T2T 5C7, Canada
The Bailey Clinic
Red Deer, Alberta, T4N 6V7, Canada
Eastern Health (MUN)
St. John's, Newfoundland and Labrador, A1B 3V6, Canada
Centre for Studies in Family Medicine
London, Ontario, N6G 2M1, Canada
St. Michael's Hospital
Toronto, Ontario, M5B 1W8, Canada
Omnispec Recherche Clinique Inc.
Mirabel, Quebec, J7J 2K8, Canada
Applied Medical Informatics Research INC.
Westmount, Quebec, H3Z 1E5, Canada
Clinique des maladies Lipidiques de Quebec
Québec, G1V 4M6, Canada
University Hospital Brno
Brno, 625 00, Czechia
Diahaza s.r.o.Intern.Med.Outpat.Clin.Dep.Diabetology,Holesov
Holešov, 769 01, Czechia
AIDIN VK s.r.o.,Department Diabetology, Hranice
Hranice, 753 01, Czechia
Univ. Hospital Kralovske Vinohrady
Prague, 100 42, Czechia
DiaGolfova s.r.o., Department Diabetology, Prague
Prague, 102 00, Czechia
Milan Kvapil s.r.o.,Diabetology ambulance,Prague
Prague, 149 00, Czechia
ResTrial s.r.o.Diabetology Ambulance,Prague
Prague, 18100, Czechia
HUS, Lihavuustutkimusyksikkö Biomedicum Helsinki
Helsinki, 00290, Finland
Mehiläinen Jyväskylä
Jyväskylä, 40100, Finland
Satakunnan Diabetesasema, Pori
Pori, 28100, Finland
FinnMedi Oy, Tampere
Tampere, 33520, Finland
TYKS
Turku, FI-20520, Finland
HOP Jean Minjoz
Besançon, 25030, France
HOP Le Creusot
Le Creusot, 71200, France
HOP Paris Saint-Joseph
Paris, 75014, France
HOP Bichat
Paris, 75018, France
HOP de Poitiers
Poitiers, 86021, France
HOP Civil
Strasbourg, 67091, France
HOP Rangueil
Toulouse Cédex 04, 31059, France
Diabetes-Klinik Bad Mergentheim GmbH & Co. KG
Bad Mergentheim, 97980, Germany
Diabetologische Schwerpunktpraxis, Bosenheim
Bosenheim, 55545, Germany
Praxis Dr. Busch, Dortmund
Dortmund, 44137, Germany
GWT-TUD GmbH
Dresden, 01307, Germany
ZKS Südbrandenburg GmbH
Elsterwerda, 04910, Germany
InnoDiab Forschung GmbH
Essen, 45136, Germany
Praxis Dr. Kaiser, Frankfurt
Frankfurt, 60388, Germany
Institut für Diabetesforschung Münster GmbH
Münster, 48145, Germany
Diabetologische Schwerpunktpraxis
Münster, 48153, Germany
Praxis Dr. Behnke, Neuwied
Neuwied, 56564, Germany
Praxis Dr. Hilgenberg
Rehburg-Loccum, 31547, Germany
"Korgialeneio-Benakeio" Hellenic Red Cross Hospital
Athens, 115 26, Greece
General Hospital of Athens "Laiko"
Athens, 11527, Greece
Univ. Gen. Hosp. of Ioannina
Ioannina, 45500, Greece
General Hospital of Nikaia
Nikaia, 18484, Greece
General Hopsital of Thessaloniki "Ippokrateio"
Thessaloniki, 54642, Greece
General Hospital of Thessaloniki "G. Papanikolaou"
Thessaloniki, 57010, Greece
Clinexpert Kft.
Budapest, 1033, Hungary
Synexus Magyarorszag Kft.
Budapest, 1036, Hungary
University Debrecen Hospital
Debrecen, 4032, Hungary
CRU Hungary Ltd, Private Practice, Miskolc
Miskolc, 3529, Hungary
Clinfan SMO Ltd.
Szekszárd, 7100, Hungary
Csongrad Country Dr Bugyi Istvan Hosp.
Szentes, 6600, Hungary
Zala Country Hospital, Diabetic Outpatient Clinic
Zalaegerszeg, 8900, Hungary
Mater Misericordiae University Hospital
Dublin, 7, Ireland
Inrca-Irccs
Ancona, 60124, Italy
A.O. Spedali Civili di Brescia
Brescia, 25123, Italy
Osp. Campo di Marte
Lucca, 55100, Italy
Azienda Ospedaliera Universitaria "Federico II"
Napoli, 80131, Italy
Policlinico Gemelli
Roma, 00168, Italy
Osp. S. Giovanni Calibita Fatebenefratelli
Roma, 00186, Italy
IRCCS Gruppo Multimedica
Sesto San Giovanni (MI), 20099, Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, 53100, Italy
Ospedale Molinette, AO Città della Salute e della
Torino, 10126, Italy
Zemgales Center of diabetes, Jelgava
Jelgava, 3001, Latvia
A. Lucenko's Internist & Endocrinologist Doctor's Practice
Liepāja, 3401, Latvia
Dace Teterovska Doctor's Practice in Endocrinology,Ogre
Ogre, 5001, Latvia
P. Stradins Clinical University Hospital, Riga
Riga, 1002, Latvia
Riga Health Center, Private Practice
Riga, 1002, Latvia
Sigulda Hospital, Outpatient department
Sigulda, 2150, Latvia
VSV Centrs, Stalte Private Practice, Talsi
Talsi, 3201, Latvia
Clínica EndocrInol en Diabetes Obesidad y Tiroides (DOT)
Aguascalientes, 20129, Mexico
Hospital Cardiologica Aguascalientes
Aguascalientes, 20230, Mexico
Unidad de Investigacion Clinica Cardiometabolica de Occident
Guadalajara, 44150, Mexico
Instituto Jaliscience de Inv. en Diabetes y Obesidad, S.C.
Guadalajara, 44600, Mexico
Unidad de Patologia Clinica
Guadalajara, CP 44650, Mexico
Noordwest Ziekenhuisgroep
Alkmaar, 1815 JD, Netherlands
Ziekenhuisgroep Twente locatie Almelo
Almelo, 7609 PP, Netherlands
Meander Medisch Centrum
Amersfoort, 3813 TZ, Netherlands
Gelre Ziekenhuizen Apeldoorn
Apeldoorn, 7334 DZ, Netherlands
EB Utrecht Research
Utrecht, 3511 NH, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
South Pacific Clinical Trials
Auckland, New Zealand, 0610, New Zealand
Lipid and Diabetes Research Group
Christchurch, 8011, New Zealand
M3 Helse AS
Hamar, N-2317, Norway
Oslo Universitetssykehus HF, Lipidklinikken
Oslo, N-0027, Norway
Stavanger Helseforskning
Stavanger, N-4068, Norway
Universitetssykehuset Nord-Norge, Tromsø
Tromsø, N-9038, Norway
DiabSerwis S.C., Chorzow
Chorzów, 41-500, Poland
Medical Centre Pratia Gdynia
Gdynia, 81-338, Poland
Medical Centre Pratia Katowice I
Katowice, 40-954, Poland
Medical Centre Pratia Krakow
Krakow, 30-002, Poland
University Hospital in Krakow
Krakow, 31-501, Poland
Independent Public Clin.Hosp.no1Lublin,Dep.Internal Diseases
Lublin, 20-081, Poland
Witold Chodzko Institute Rural Medic,Dep.Diabetology,Lublin
Lublin, 20-090, Poland
Reg.Spec.Hosp.Olsztyn,Clin,Endocrinology,Diabetics.&Int.Med.
Olsztyn, 10-561, Poland
Clinical Research Center Medicome, Oswiecim
Oświęcim, 32-600, Poland
Omedica Medical Centre, Poznan
Poznan, 60-111, Poland
Medical Centre Pratia Warszawa
Warsaw, 01-868, Poland
NZOZ Med-Art.Specialist Clinics, Zory
Żory, 44-240, Poland
Hospital de Braga-Escala Braga
Braga, 4710-243, Portugal
Centro Hospitalar da Cova da Beira Hospital Pêro da Covilhã
Covilha, 6200-251, Portugal
APDP - Associação Protectora dos Diabéticos de Portugal
Lisbon, 1250-189, Portugal
H. Santo António - Centro Hospitalar do Porto
Porto, 4099-001, Portugal
Centro Hospitalar São João,EPE
Porto, 4200-319, Portugal
ULSAM, EPE - Hospital de Santa Luzia
Viana do Castelo, 4901-858, Portugal
Centro Hospitalar de Vila Nova de Gaia
Vila Nova de Gaia, 4400-129, Portugal
Nicodiab SRL, Bucharest
Bucharest, 010507, Romania
Milit. Cent. Emerg. Univ. Hosp. Dr. Davila, Met. Dis. Dept.
Bucharest, 010825, Romania
SC Medical Centre "Sanatatea Ta" SRL, Bucharest
Bucharest, 020603, Romania
SC Pelican Impex SRL, Cabinet Nr. 201, Diabetes Dept.
Oradea, Bihor County, 410469, Romania
Centrul Medical Dr Negrisanu SRL
Timișoara, 300456, Romania
City Clinical Hospital no. 67, Moscow
Moscow, 123423, Russia
CJSC"Polyclinic complex",Dep.Endocrinology,St.Petersburg
Saint Petersburg, 190013, Russia
City Outpatient dep.no.107;clinc.pharmacology,st.petersburg
Saint Petersburg, 195030, Russia
Medical Academy named after I. Mechnikov, St. Petersburg
Saint Petersburg, 195067, Russia
City Hospital Saint Elizaveta, Dept. Endocrinology
Saint Petersburg, 195257, Russia
Policlinic No. 1 of Russian Academy of Sciences, St. Petersburg
Saint Petersburg, 199034, Russia
LCS Clinical Research Unit
Bryanston, 2021, South Africa
TREAD Research
Cape Town, 7530, South Africa
Dr Hilton Kaplan
Cape Town, 7708, South Africa
Dr. L. A.Distiller
Johannesburg, 2198, South Africa
VX Pharma (Pty) Ltd Pretoria
Pretoria, 0087, South Africa
Diabetes Care Centre
Pretoria, 0181, South Africa
Hospital A Coruña
A Coruña, 15006, Spain
CM Avances Médicos
Granada, 18003, Spain
Hospital de la Inmaculada Concepción
Granada, 18004, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Hospital Universitario Infanta Leonor
Madrid, 28031, Spain
Endo-Diabesidad-Clínica Durán & Asociados
Seville, 41018, Spain
Hospital Virgen Macarena
Seville, 41071, Spain
Hospital Clínico de Valencia
Valencia, 46010, Spain
Ängelholms Sjukhus
Ängelholm, 262 81, Sweden
CTC Sahlgrenska Universitetssjukhuset
Gothenburg, 413 45, Sweden
Karlskoga lasarett
Karlskoga, 691 81, Sweden
Skånes universitetssjukhus, Lund
Lund, 221 85, Sweden
S3 Clinical Research Centers
Vällingby, 162 68, Sweden
Royal Bournemouth and Christchurch Hospital
Bournemouth, BH7 7DW, United Kingdom
Bradford Royal Infirmary
Bradford, BD9 6RJ, United Kingdom
Hull Royal Infirmary
Hull, HU3 2RW, United Kingdom
Ipswich Hospital
Ipswich, IP4 5PD, United Kingdom
Leicester General Hospital
Leicester, LE5 4PW, United Kingdom
Guy's Hospital
London, SE1 9RT, United Kingdom
King's College Hospital
London, SE5 9RJ, United Kingdom
St Mary's Hospital
London, W2 1NY, United Kingdom
James Cook University Hospital
Middlesbrough, TS4 3BW, United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne, NE1 4LP, United Kingdom
Queen's Medical Centre
Nottingham, NG7 2UH, United Kingdom
George Eliot Hospital
Nuneaton, CV10 7DJ, United Kingdom
Related Publications (2)
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.
PMID: 37616393DERIVEDRosenstock 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.
PMID: 30287422DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Center
- Organization
- Boehringer Ingelheim
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 19, 2015
First Posted
October 20, 2015
Study Start
December 22, 2015
Primary Completion
September 12, 2017
Study Completion
September 20, 2017
Last Updated
November 2, 2018
Results First Posted
November 2, 2018
Record last verified: 2018-10