Clinical trial NCT02580591: Empagliflozin as Adjunctive to Insulin Therapy Over 26 Weeks in Patients With T1DM (EASE-3)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2015-10-20
Enrollment: 977
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 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


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
* Compliance with trial medication administration between 80% and 120% during placebo run-in period Further inclusion criteria apply

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
* Intake of an investigational drug in another trial within last 30 days Further exclusion criteria apply

Primary outcomes:
measure: Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 for Full Analysis Set (FAS) (Observed Cases [OC])
timeFrame: Baseline to week 26
measure: 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))
timeFrame: Baseline to week 26
Secondary outcomes:
measure: Rate Per Patient-year of Investigator-reported Symptomatic Hypoglycemic Adverse Events (AEs) With Confirmed Plasma Glucose (PG)
timeFrame: Week 5 to Week 26, Week 1 to Week 26
measure: Change From Baseline in Body Weight at Week 26
timeFrame: Baseline to week 26
measure: Change From Baseline in Total Daily Insulin Dose (TDID) at Week 26
timeFrame: Baseline to week 26
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 26
timeFrame: Baseline to week 26
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: Healthscan Clinical Trials LLC
state: Alabama
city: Concord
country: United States
facility: John Muir Physician Network Clinical Research Center
state: California
city: Fresno
country: United States
facility: Valley Research
state: California
city: Greenbrae
country: United States
facility: Marin Endocrine Care and Research
state: California
city: Oakland
country: United States
facility: Pacific Research Partners, LLC
state: California
city: San Ramon
country: United States
facility: NorCal Endocrinology and Internal Medicine
state: California
city: Santa Barbara
country: United States
facility: William Sansum Diabetes Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Hialeah
country: United States
facility: International Research Associates, LLC
state: Florida
city: Jacksonville
country: United States
facility: Solutions Through Advanced Research, Inc.
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc.
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Lawrenceville
country: United States
facility: Physicians Research Associates, LLC
state: Georgia
city: Marietta
country: United States
facility: Sestron Clinical Research
state: Georgia
city: Stockbridge
country: United States
facility: Eagle's Landing Diabetes and Endocrinology
state: Georgia
city: Arlington Heights
country: United States
facility: Northwest Endo Diabetes Research, LLC
state: Illinois
city: Lexington
country: United States
facility: Kentucky Diabetes Endocrinology Center
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: MODEL Clinical Research
state: Maryland
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Henderson
country: United States
facility: Desert Endocrinology Clinical Research Center
state: Nevada
city: Las Vegas
country: United States
facility: Palm Research Center
state: Nevada
city: Rochester
country: United States
facility: Endocrine-Diabetes Care and Resource Center
state: New York
city: Smithtown
country: United States
facility: Endocrine Associates of Long Island, PC
state: New York
city: Williamsville
country: United States
facility: Diabetes Endocrinology Research Center of Western New York
state: New York
city: Morehead City
country: United States
facility: Diabetes and Endocrinology Consultants, PC
state: North Carolina
city: Gallipolis
country: United States
facility: Holzer Clinic LLC
state: Ohio
city: Oklahoma City
country: United States
facility: COR Clinical Research, LLC
state: Oklahoma
city: Myrtle Beach
country: United States
facility: Strand Physician Specialists dba Carolina Health Specialists
state: South Carolina
city: Bartlett
country: United States
facility: AM Diabetes and Endocrinology Center
state: Tennessee
city: Bristol
country: United States
facility: Holston Medical Group
state: Tennessee
city: Chattanooga
country: United States
facility: University Diabetes and Endocrine Consultants
state: Tennessee
city: Austin
country: United States
facility: Texas Diabetes & Endocrinology PA
state: Texas
city: Dallas
country: United States
facility: Texas Health Physicians Group
state: Texas
city: Dallas
country: United States
facility: Dallas Diabetes and Endocrine Center
state: Texas
city: Dallas
country: United States
facility: Research Institute of Dallas
state: Texas
city: San Antonio
country: United States
facility: Endeavor Clinical Trials, PA
state: Texas
city: Chesapeake
country: United States
facility: Virginia Endocrinology Research
state: Virginia
city: Coffs Harbour
country: Australia
facility: Coffs Endocrine & Diabetes Services
state: New South Wales
city: Elizabeth Vale
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Keswick
country: Australia
facility: SA Endocrine Research P/L
state: South Australia
city: East Ringwood
country: Australia
facility: Eastern Clinical Research Unit
state: Victoria
city: Calgary
country: Canada
facility: Richmond Road and Diagnostic Treatment Centre
state: Alberta
city: Red Deer
country: Canada
facility: The Bailey Clinic
state: Alberta
city: St. John's
country: Canada
facility: Eastern Health (MUN)
state: Newfoundland and Labrador
city: London
country: Canada
facility: Centre for Studies in Family Medicine
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Mirabel
country: Canada
facility: Omnispec Recherche Clinique Inc.
state: Quebec
city: Westmount
country: Canada
facility: Applied Medical Informatics Research INC.
state: Quebec
city: Quebec
country: Canada
facility: Clinique des maladies Lipidiques de Quebec
city: Brno
country: Czechia
facility: University Hospital Brno
city: Holesov
country: Czechia
facility: Diahaza s.r.o.Intern.Med.Outpat.Clin.Dep.Diabetology,Holesov
city: Hranice
country: Czechia
facility: AIDIN VK s.r.o.,Department Diabetology, Hranice
city: Prague
country: Czechia
facility: Univ. Hospital Kralovske Vinohrady
city: Prague
country: Czechia
facility: DiaGolfova s.r.o., Department Diabetology, Prague
city: Prague
country: Czechia
facility: Milan Kvapil s.r.o.,Diabetology ambulance,Prague
city: Prague
country: Czechia
facility: ResTrial s.r.o.Diabetology Ambulance,Prague
city: Helsinki
country: Finland
facility: HUS, Lihavuustutkimusyksikkö Biomedicum Helsinki
city: Jyväskylä
country: Finland
facility: Mehiläinen Jyväskylä
city: Pori
country: Finland
facility: Satakunnan Diabetesasema, Pori
city: Tampere
country: Finland
facility: FinnMedi Oy, Tampere
city: Turku
country: Finland
facility: TYKS
city: Besancon
country: France
facility: HOP Jean Minjoz
city: Le Creusot
country: France
facility: HOP Le Creusot
city: Paris
country: France
facility: HOP Paris Saint-Joseph
city: Paris
country: France
facility: HOP Bichat
city: Poitiers
country: France
facility: HOP de Poitiers
city: Strasbourg
country: France
facility: HOP Civil
city: Toulouse Cédex 04
country: France
facility: HOP Rangueil
city: Bad Mergentheim
country: Germany
facility: Diabetes-Klinik Bad Mergentheim GmbH & Co. KG
city: Bosenheim
country: Germany
facility: Diabetologische Schwerpunktpraxis, Bosenheim
city: Dortmund
country: Germany
facility: Praxis Dr. Busch, Dortmund
city: Dresden
country: Germany
facility: GWT-TUD GmbH
city: Elsterwerda
country: Germany
facility: ZKS Südbrandenburg GmbH
city: Essen
country: Germany
facility: InnoDiab Forschung GmbH
city: Frankfurt
country: Germany
facility: Praxis Dr. Kaiser, Frankfurt
city: Münster
country: Germany
facility: Institut für Diabetesforschung Münster GmbH
city: Münster
country: Germany
facility: Diabetologische Schwerpunktpraxis
city: Neuwied
country: Germany
facility: Praxis Dr. Behnke, Neuwied
city: Rehburg-Loccum
country: Germany
facility: Praxis Dr. Hilgenberg
city: Athens
country: Greece
facility: "Korgialeneio-Benakeio" Hellenic Red Cross Hospital
city: Athens
country: Greece
facility: General Hospital of Athens "Laiko"
city: Ioannina
country: Greece
facility: Univ. Gen. Hosp. of Ioannina
city: Nikaia
country: Greece
facility: General Hospital of Nikaia
city: Thessaloniki
country: Greece
facility: General Hopsital of Thessaloniki "Ippokrateio"
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolaou"
city: Budapest
country: Hungary
facility: Clinexpert Kft.
city: Budapest
country: Hungary
facility: Synexus Magyarorszag Kft.
city: Debrecen
country: Hungary
facility: University Debrecen Hospital
city: Miskolc
country: Hungary
facility: CRU Hungary Ltd, Private Practice, Miskolc
city: Szekszard
country: Hungary
facility: Clinfan SMO Ltd.
city: Szentes
country: Hungary
facility: Csongrad Country Dr Bugyi Istvan Hosp.
city: Zalaegerszeg
country: Hungary
facility: Zala Country Hospital, Diabetic Outpatient Clinic
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Ancona
country: Italy
facility: Inrca-Irccs
city: Brescia
country: Italy
facility: A.O. Spedali Civili di Brescia
city: Lucca
country: Italy
facility: Osp. Campo di Marte
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II"
city: Roma
country: Italy
facility: Policlinico Gemelli
city: Roma
country: Italy
facility: Osp. S. Giovanni Calibita Fatebenefratelli
city: Sesto San Giovanni (MI)
country: Italy
facility: IRCCS Gruppo Multimedica
city: Siena
country: Italy
facility: A.O.U. Senese Policlinico Santa Maria alle Scotte
city: Torino
country: Italy
facility: Ospedale Molinette, AO Città della Salute e della
city: Jelgava
country: Latvia
facility: Zemgales Center of diabetes, Jelgava
city: Liepaja
country: Latvia
facility: A. Lucenko's Internist & Endocrinologist Doctor's Practice
city: Ogre
country: Latvia
facility: Dace Teterovska Doctor's Practice in Endocrinology,Ogre
city: Riga
country: Latvia
facility: P. Stradins Clinical University Hospital, Riga
city: Riga
country: Latvia
facility: Riga Health Center, Private Practice
city: Sigulda
country: Latvia
facility: Sigulda Hospital, Outpatient department
city: Talsi
country: Latvia
facility: VSV Centrs, Stalte Private Practice, Talsi
city: Aguascalientes
country: Mexico
facility: Clínica EndocrInol en Diabetes Obesidad y Tiroides (DOT)
city: Aguascalientes
country: Mexico
facility: Hospital Cardiologica Aguascalientes
city: Guadalajara
country: Mexico
facility: Unidad de Investigacion Clinica Cardiometabolica de Occident
city: Guadalajara
country: Mexico
facility: Instituto Jaliscience de Inv. en Diabetes y Obesidad, S.C.
city: Guadalajara
country: Mexico
facility: Unidad de Patologia Clinica
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente locatie Almelo
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen Apeldoorn
city: Utrecht
country: Netherlands
facility: EB Utrecht Research
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Auckland, New Zealand
country: New Zealand
facility: South Pacific Clinical Trials
city: Christchurch
country: New Zealand
facility: Lipid and Diabetes Research Group
city: Hamar
country: Norway
facility: M3 Helse AS
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Lipidklinikken
city: Stavanger
country: Norway
facility: Stavanger Helseforskning
city: Tromsø
country: Norway
facility: Universitetssykehuset Nord-Norge, Tromsø
city: Chorzow
country: Poland
facility: DiabSerwis S.C., Chorzow
city: Gdynia
country: Poland
facility: Medical Centre Pratia Gdynia
city: Katowice
country: Poland
facility: Medical Centre Pratia Katowice I
city: Krakow
country: Poland
facility: Medical Centre Pratia Krakow
city: Krakow
country: Poland
facility: University Hospital in Krakow
city: Lublin
country: Poland
facility: Independent Public Clin.Hosp.no1Lublin,Dep.Internal Diseases
city: Lublin
country: Poland
facility: Witold Chodzko Institute Rural Medic,Dep.Diabetology,Lublin
city: Olsztyn
country: Poland
facility: Reg.Spec.Hosp.Olsztyn,Clin,Endocrinology,Diabetics.&Int.Med.
city: Oswiecim
country: Poland
facility: Clinical Research Center Medicome, Oswiecim
city: Poznan
country: Poland
facility: Omedica Medical Centre, Poznan
city: Warsaw
country: Poland
facility: Medical Centre Pratia Warszawa
city: Zory
country: Poland
facility: NZOZ Med-Art.Specialist Clinics, Zory
city: Braga
country: Portugal
facility: Hospital de Braga-Escala Braga
city: Covilhã
country: Portugal
facility: Centro Hospitalar da Cova da Beira Hospital Pêro da Covilhã
city: Lisboa
country: Portugal
facility: APDP - Associação Protectora dos Diabéticos de Portugal
city: Porto
country: Portugal
facility: H. Santo António - Centro Hospitalar do Porto
city: Porto
country: Portugal
facility: Centro Hospitalar São João,EPE
city: Viana do Castelo
country: Portugal
facility: ULSAM, EPE - Hospital de Santa Luzia
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia
city: Bucharest
country: Romania
facility: Nicodiab SRL, Bucharest
city: Bucharest
country: Romania
facility: Milit. Cent. Emerg. Univ. Hosp. Dr. Davila, Met. Dis. Dept.
city: Bucharest
country: Romania
facility: SC Medical Centre "Sanatatea Ta" SRL, Bucharest
city: Oradea, Bihor County
country: Romania
facility: SC Pelican Impex SRL, Cabinet Nr. 201, Diabetes Dept.
city: Timisoara
country: Romania
facility: Centrul Medical Dr Negrisanu SRL
city: Moscow
country: Russian Federation
facility: City Clinical Hospital no. 67, Moscow
city: St. Petersburg
country: Russian Federation
facility: CJSC"Polyclinic complex",Dep.Endocrinology,St.Petersburg
city: St. Petersburg
country: Russian Federation
facility: City Outpatient dep.no.107;clinc.pharmacology,st.petersburg
city: St. Petersburg
country: Russian Federation
facility: Medical Academy named after I. Mechnikov, St. Petersburg
city: St. Petersburg
country: Russian Federation
facility: City Hospital Saint Elizaveta, Dept. Endocrinology
city: St. Petersburg
country: Russian Federation
facility: Policlinic No. 1 of Russian Academy of Sciences, St. Petersburg
city: Bryanston
country: South Africa
facility: LCS Clinical Research Unit
city: Cape Town
country: South Africa
facility: TREAD Research
city: Cape Town
country: South Africa
facility: Dr Hilton Kaplan
city: Johannesburg
country: South Africa
facility: Dr. L. A.Distiller
city: Pretoria
country: South Africa
facility: VX Pharma (Pty) Ltd Pretoria
city: Pretoria
country: South Africa
facility: Diabetes Care Centre
city: A Coruña
country: Spain
facility: Hospital A Coruña
city: Granada
country: Spain
facility: CM Avances Médicos
city: Granada
country: Spain
facility: Hospital de la Inmaculada Concepción
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Sevilla
country: Spain
facility: Endo-Diabesidad-Clínica Durán & Asociados
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Göteborg
country: Sweden
facility: CTC Sahlgrenska Universitetssjukhuset
city: Karlskoga
country: Sweden
facility: Karlskoga lasarett
city: Lund
country: Sweden
facility: Skånes universitetssjukhus, Lund
city: Vällingby
country: Sweden
facility: S3 Clinical Research Centers
city: Ängelholm
country: Sweden
facility: Ängelholms Sjukhus
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth and Christchurch Hospital
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: St Mary's Hospital
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.