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

Diabetes Mellitus, Type 1 Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02580591
• Other study ID #: 1245.72
• Secondary ID: 2014-005256-26
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2015
• Est. completion date: September 20, 2017

Study information

• Verified date: October 2018
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 977
• Est. completion date: September 20, 2017
• Est. primary completion date: September 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• Empagliflozin

• Placebo
For blinding purposes

Locations

Country	Name	City	State
Australia	Coffs Endocrine & Diabetes Services	Coffs Harbour	New South Wales
Australia	Eastern Clinical Research Unit	East Ringwood	Victoria
Australia	Lyell McEwin Hospital	Elizabeth Vale	South Australia
Australia	SA Endocrine Research P/L	Keswick	South Australia
Canada	Richmond Road and Diagnostic Treatment Centre	Calgary	Alberta
Canada	Centre for Studies in Family Medicine	London	Ontario
Canada	Omnispec Recherche Clinique Inc.	Mirabel	Quebec
Canada	Clinique des maladies Lipidiques de Quebec	Quebec
Canada	The Bailey Clinic	Red Deer	Alberta
Canada	Eastern Health (MUN)	St. John's	Newfoundland and Labrador
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Applied Medical Informatics Research INC.	Westmount	Quebec
Czechia	University Hospital Brno	Brno
Czechia	Diahaza s.r.o.Intern.Med.Outpat.Clin.Dep.Diabetology,Holesov	Holesov
Czechia	AIDIN VK s.r.o.,Department Diabetology, Hranice	Hranice
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	Univ. Hospital Kralovske Vinohrady	Prague
Finland	HUS, Lihavuustutkimusyksikkö Biomedicum Helsinki	Helsinki
Finland	Mehiläinen Jyväskylä	Jyväskylä
Finland	Satakunnan Diabetesasema, Pori	Pori
Finland	FinnMedi Oy, Tampere	Tampere
Finland	TYKS	Turku
France	HOP Jean Minjoz	Besancon
France	HOP Le Creusot	Le Creusot
France	HOP Bichat	Paris
France	HOP Paris Saint-Joseph	Paris
France	HOP de Poitiers	Poitiers
France	HOP Civil	Strasbourg
France	HOP Rangueil	Toulouse Cédex 04
Germany	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	Diabetologische Schwerpunktpraxis	Münster
Germany	Institut für Diabetesforschung Münster GmbH	Münster
Germany	Praxis Dr. Behnke, Neuwied	Neuwied
Germany	Praxis Dr. Hilgenberg	Rehburg-Loccum
Greece	"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
Hungary	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.	Szekszard
Hungary	Csongrad Country Dr Bugyi Istvan Hosp.	Szentes
Hungary	Zala Country Hospital, Diabetic Outpatient Clinic	Zalaegerszeg
Ireland	Mater Misericordiae University Hospital	Dublin
Italy	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	Osp. S. Giovanni Calibita Fatebenefratelli	Roma
Italy	Policlinico Gemelli	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
Latvia	Zemgales Center of diabetes, Jelgava	Jelgava
Latvia	A. Lucenko's Internist & Endocrinologist Doctor's Practice	Liepaja
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
Mexico	Clínica EndocrInol en Diabetes Obesidad y Tiroides (DOT)	Aguascalientes
Mexico	Hospital Cardiologica Aguascalientes	Aguascalientes
Mexico	Instituto Jaliscience de Inv. en Diabetes y Obesidad, S.C.	Guadalajara
Mexico	Unidad de Investigacion Clinica Cardiometabolica de Occident	Guadalajara
Mexico	Unidad de Patologia Clinica	Guadalajara
Netherlands	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
New Zealand	South Pacific Clinical Trials	Auckland, New Zealand
New Zealand	Lipid and Diabetes Research Group	Christchurch
Norway	M3 Helse AS	Hamar
Norway	Oslo Universitetssykehus HF, Lipidklinikken	Oslo
Norway	Stavanger Helseforskning	Stavanger
Norway	Universitetssykehuset Nord-Norge, Tromsø	Tromsø
Poland	DiabSerwis S.C., Chorzow	Chorzow
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	Oswiecim
Poland	Omedica Medical Centre, Poznan	Poznan
Poland	Medical Centre Pratia Warszawa	Warsaw
Poland	NZOZ Med-Art.Specialist Clinics, Zory	Zory
Portugal	Hospital de Braga-Escala Braga	Braga
Portugal	Centro Hospitalar da Cova da Beira Hospital Pêro da Covilhã	Covilhã
Portugal	APDP - Associação Protectora dos Diabéticos de Portugal	Lisboa
Portugal	Centro Hospitalar São João,EPE	Porto
Portugal	H. Santo António - Centro Hospitalar do Porto	Porto
Portugal	ULSAM, EPE - Hospital de Santa Luzia	Viana do Castelo
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova de Gaia
Romania	Milit. Cent. Emerg. Univ. Hosp. Dr. Davila, Met. Dis. Dept.	Bucharest
Romania	Nicodiab SRL, Bucharest	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	Timisoara
Russian Federation	City Clinical Hospital no. 67, Moscow	Moscow
Russian Federation	City Hospital Saint Elizaveta, Dept. Endocrinology	St. Petersburg
Russian Federation	City Outpatient dep.no.107;clinc.pharmacology,st.petersburg	St. Petersburg
Russian Federation	CJSC"Polyclinic complex",Dep.Endocrinology,St.Petersburg	St. Petersburg
Russian Federation	Medical Academy named after I. Mechnikov, St. Petersburg	St. Petersburg
Russian Federation	Policlinic No. 1 of Russian Academy of Sciences, St. Petersburg	St. Petersburg
South Africa	LCS Clinical Research Unit	Bryanston
South Africa	Dr Hilton Kaplan	Cape Town
South Africa	TREAD Research	Cape Town
South Africa	Dr. L. A.Distiller	Johannesburg
South Africa	Diabetes Care Centre	Pretoria
South Africa	VX Pharma (Pty) Ltd Pretoria	Pretoria
Spain	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	Sevilla
Spain	Hospital Virgen Macarena	Sevilla
Spain	Hospital Clínico de Valencia	Valencia
Sweden	Ängelholms Sjukhus	Ängelholm
Sweden	CTC Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Karlskoga lasarett	Karlskoga
Sweden	Skånes universitetssjukhus, Lund	Lund
Sweden	S3 Clinical Research Centers	Vällingby
United Kingdom	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 States	Northwest Endo Diabetes Research, LLC	Arlington Heights	Illinois
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Texas Diabetes & Endocrinology PA	Austin	Texas
United States	MODEL Clinical Research	Baltimore	Maryland
United States	University of Maryland School of Medicine	Baltimore	Maryland
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	Virginia Endocrinology Research	Chesapeake	Virginia
United States	John Muir Physician Network Clinical Research Center	Concord	California
United States	Dallas Diabetes and Endocrine Center	Dallas	Texas
United States	Research Institute of Dallas	Dallas	Texas
United States	Texas Health Physicians Group	Dallas	Texas
United States	Valley Research	Fresno	California
United States	Holzer Clinic LLC	Gallipolis	Ohio
United States	Marin Endocrine Care and Research	Greenbrae	California
United States	Desert Endocrinology Clinical Research Center	Henderson	Nevada
United States	International Research Associates, LLC	Hialeah	Florida
United States	Solutions Through Advanced Research, Inc.	Jacksonville	Florida
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	Palm Research Center	Las Vegas	Nevada
United States	Physicians Research Associates, LLC	Lawrenceville	Georgia
United States	Kentucky Diabetes Endocrinology Center	Lexington	Kentucky
United States	Sestron Clinical Research	Marietta	Georgia
United States	University of Miami	Miami	Florida
United States	Healthscan Clinical Trials LLC	Montgomery	Alabama
United States	Diabetes and Endocrinology Consultants, PC	Morehead City	North Carolina
United States	Strand Physician Specialists dba Carolina Health Specialists	Myrtle Beach	South Carolina
United States	Suncoast Clinical Research, Inc.	New Port Richey	Florida
United States	Pacific Research Partners, LLC	Oakland	California
United States	COR Clinical Research, LLC	Oklahoma City	Oklahoma
United States	Endocrine-Diabetes Care and Resource Center	Rochester	New York
United States	Endeavor Clinical Trials, PA	San Antonio	Texas
United States	NorCal Endocrinology and Internal Medicine	San Ramon	California
United States	William Sansum Diabetes Center	Santa Barbara	California
United States	Endocrine Associates of Long Island, PC	Smithtown	New York
United States	Eagle's Landing Diabetes and Endocrinology	Stockbridge	Georgia
United States	Diabetes Endocrinology Research Center of Western New York	Williamsville	New York

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Rate Per Patient-year of Investigator-reported Symptomatic Hypoglycemic Adverse Events (AEs) With Confirmed Plasma Glucose (PG)	Rate per patient-year of investigator-reported symptomatic hypoglycemic adverse events (AEs) with confirmed plasma glucose (PG) <54 milligram per deciliter (mg/dL) (<3.0 millimoles per litre (mmol/L)) and/or severe hypoglycemic AEs (i.e. all investigator-reported AEs that had confirmed PG <54 mg/dL [<3.0 mmol/L] with symptoms reported and all severe hypoglycemic events that were confirmed by adjudication) is presented for (i) From week 5 to 26 and (ii) From week 1 to 26. Least squares mean is actually an adjusted event rate. This is key secondary endpoints.	Week 5 to Week 26, Week 1 to Week 26
Secondary	Change From Baseline in Body Weight at Week 26	Change from baseline in body weight 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	Change From Baseline in Total Daily Insulin Dose (TDID) at Week 26	Change from baseline in Total daily insulin dose (TDID) 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	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 26	Change from baseline in Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) 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