Empagliflozin as Adjunctive to InSulin thErapy Over 52 Weeks in Patients With Type 1 Diabetes Mellitus (EASE-2)

NCT ID: NCT02414958

Last Updated: 2019-01-03

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

730 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-30

Study Completion Date

2017-10-23

Brief Summary

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Comparison of 2 doses of empagliflozin vs placebo in patients already using either an insulin regimen of multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Randomisation to 3 treatments arms (equal assignment) following a screening period, an optimisation period and a run-in period. 52 week double-blind treatment period, and 3 week follow-up period.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Study Groups

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Empagliflozin low dose

Empagliflozin tablets once daily

Group Type EXPERIMENTAL

Empagliflozin

Intervention Type DRUG

Empagliflozin high dose

Empagliflozin tablets once daily

Group Type EXPERIMENTAL

Empagliflozin

Intervention Type DRUG

Placebo

Placebo tablets matching empagliflozin once daily

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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Empagliflozin

Intervention Type DRUG

Empagliflozin

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female patient receiving insulin for the treatment of documented diagnosis of Type 1 Diabetes Mellitus (T1DM) for at least 1 year at the time of Visit 1
* Fasting C-peptide value of \< 0.7 ng/mL (0.23 nmol/L) at Visit 2 measured by the central laboratory
* Use of, and be willing, based on the Investigator's judgement, to continue throughout the duration of the trial, either:

* Multiple Daily Injections (MDI) of insulin consisting of at least one basal insulin injection and at least three daily bolus injections OR
* Continuous Subcutaneous Insulin Infusion (CSII) of any insulin type, with at least 5 months experience of using CSII prior to Visit 1
* HbA1c \>/= 7.5% and \</= 10.0% at Visit 5 measured by the central laboratory
* Age \>/= 18 years at Visit 1

Exclusion Criteria

* History of Type 2 Diabetes Mellitus (T2DM), 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 (e.g. metformin, alpha-glucosidase inhibitors, Glucagon-like-peptide 1 (GLP-1) analogues, Sodium-Glucose Co-Transporter (SGLT-2) inhibitors, pramlintide, inhaled insulin, pre-mixed insulins etc.) except subcutaneous basal and bolus insulin within 3 months prior to Visit 1
* Occurrence of severe hypoglycaemia involving coma/unconsciousness and/or seizure that required hospitalisation or hypoglycaemia-related treatment by an emergency physician or paramedic within 3 months prior to Visit 1 and until randomisation
* Occurence of Diabetic Ketoacidosis (DKA) within 3 months prior to Visit 1 and until randomisation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

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AMCR Institute, Inc.

Escondido, California, United States

Site Status

Diabetes/Lipid Management and Research Center

Huntington Beach, California, United States

Site Status

National Research Institute

Los Angeles, California, United States

Site Status

Mills-Peninsula Health Services

San Mateo, California, United States

Site Status

Metabolic Institute of America

Tarzana, California, United States

Site Status

University Clinical Investigators, Inc.

Tustin, California, United States

Site Status

Creekside Endocrine Associates, PC

Denver, Colorado, United States

Site Status

The Center for Diabetes and Endocrine Care

Fort Lauderdale, Florida, United States

Site Status

East Coast Institute for Research, LLC

Jacksonville, Florida, United States

Site Status

Baptist Diabetes Associates, PA

Miami, Florida, United States

Site Status

Physicians Research Associates, LLC

Lawrenceville, Georgia, United States

Site Status

Endocrine Research Solutions, Inc.

Roswell, Georgia, United States

Site Status

Rocky Mountain Diabetes and Osteoporosis Center

Idaho Falls, Idaho, United States

Site Status

Northwest Endo Diabetes Research, LLC

Arlington Heights, Illinois, United States

Site Status

Midwest Endocrinology

Crystal Lake, Illinois, United States

Site Status

Iowa Diabetes and Endocrinology Research Center

West Des Moines, Iowa, United States

Site Status

Diabetes anddocrine Associates, PC

Omaha, Nebraska, United States

Site Status

Desert Endocrinology Clinical Research Center

Henderson, Nevada, United States

Site Status

Palm Research Center

Las Vegas, Nevada, United States

Site Status

Southern New Hampshire Diabetes and Endocrinology

Nashua, New Hampshire, United States

Site Status

Albany Medical Center / Albany Medical College

Albany, New York, United States

Site Status

University Physicians Group Research Division

Staten Island, New York, United States

Site Status

Diabetes and Endocrinology Consultants, PC

Morehead City, North Carolina, United States

Site Status

The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital

Cincinnati, Ohio, United States

Site Status

Diabetes and Obesity Clinical Trials Center

Nashville, Tennessee, United States

Site Status

North Texas Endocrine Center

Dallas, Texas, United States

Site Status

Office of Dr. Michelle Zaniewski-Singh

Houston, Texas, United States

Site Status

Texas Diabetes and Endocrinology

Round Rock, Texas, United States

Site Status

Bateman Horne Center

Salt Lake City, Utah, United States

Site Status

Advanced Research Institute

South Ogden, Utah, United States

Site Status

Larry D Stonesifer, MD Inc., PS

Federal Way, Washington, United States

Site Status

Rainier Clinical Research Center, Inc

Renton, Washington, United States

Site Status

The Polyclinic

Seattle, Washington, United States

Site Status

MultiCare Institute for Research and Innovation

Tacoma, Washington, United States

Site Status

Coffs Endocrine & Diabetes Services

Coffs Harbour, New South Wales, Australia

Site Status

AIM Centre

Merewether, New South Wales, Australia

Site Status

Royal Brisbane & Women's Hospital-Endocrinology

Herston, Queensland, Australia

Site Status

VIVIT Instit.am LKH Feldkirch,Abt.f.Innere Med.u.Kardiologie

Feldkirch, , Austria

Site Status

LKH Steyr, Kardiologie

Steyr, , Austria

Site Status

KH Rudolfstiftung, 1. Med. Abt., Wien

Vienna, , Austria

Site Status

Hospital Hietzing

Vienna, , Austria

Site Status

Arlon - HOSP Sud Luxembourg - Vivalia

Arlon, , Belgium

Site Status

Bonheiden - HOSP Imelda

Bonheiden, , Belgium

Site Status

ULB Hopital Erasme

Brussels, , Belgium

Site Status

Brussels - UNIV UZ Brussel

Brussels, , Belgium

Site Status

Edegem - UNIV UZ Antwerpen

Edegem, , Belgium

Site Status

UNIV UZ Gent

Ghent, , Belgium

Site Status

La Louvière - UNIV CHU Tivoli

La Louvière, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Centre Hospitalier Universitaire de Liège

Liège, , Belgium

Site Status

Liège - HOSP CHR de la Citadelle

Liège, , Belgium

Site Status

Merksem - HOSP ZNA Jan Palfijn

Merksem, , Belgium

Site Status

LMC Endocrinology Centres (Calgary) Ltd.

Calgary, Alberta, Canada

Site Status

The Bailey Clinic

Red Deer, Alberta, Canada

Site Status

Royal Jubilee Hospital

Victoria, British Columbia, Canada

Site Status

Health Sciences Centre Winnipeg

Winnipeg, Manitoba, Canada

Site Status

CHUM - Pavillon R

Montreal, Migration Data, Canada

Site Status

Capital District Health Auth.

Halifax, Nova Scotia, Canada

Site Status

Kingston General Hospital

Kingston, Ontario, Canada

Site Status

LMC Thornhill/Vaughan

Thornhill, Ontario, Canada

Site Status

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status

Royal Victoria Hospital

Montreal, Quebec, Canada

Site Status

General Univ.hosp.in Prague (VFN), Diabetes ambulance

Prague, , Czechia

Site Status

Diabetology and Internal Practice Dr. Vladimir Lelek

Slaný, , Czechia

Site Status

Masaryk Hospital, Internal Department

Ústí nad Labem, , Czechia

Site Status

Aalborg Sygehus Syd

Aalborg, , Denmark

Site Status

Aarhus Universitets Hospital

Aarhus C, , Denmark

Site Status

Steno Diabetes Center Copenhagen

Gentofte Municipality, , Denmark

Site Status

Nordsjællands Hospital - Hillerød

Hillerød, , Denmark

Site Status

Køge Sygehus

Køge, , Denmark

Site Status

IteLasaretti

Kuopio, , Finland

Site Status

Terveystalo Oulu, Diapolis

Oulu, , Finland

Site Status

TYKS

Turku, , Finland

Site Status

HOP Côte de Nacre

Caen, , France

Site Status

HOP Saint-Louis

La Rochelle, , France

Site Status

HOP de Narbonne, diabéto endo, Narbonne

Narbonne, , France

Site Status

HOP Robert Debré

Reims, , France

Site Status

HOP de Brabois

Vandœuvre-lès-Nancy, , France

Site Status

HOP les Portes du Sud, Diabéto, Vénissieux

Vénissieux, , France

Site Status

Studienzentrum Aschaffenburg

Aschaffenburg, , Germany

Site Status

Gemeinschaftspraxis, Asslar

Aßlar, , Germany

Site Status

ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH

Berlin, , Germany

Site Status

InnoDiab Forschung GmbH

Essen, , Germany

Site Status

Praxis Dr. Kosch, Pirna

Pirna, , Germany

Site Status

Allgemeinmedizinische und Diabetologische Schwerpunktpraxis

Rehlingen-Siersburg, , Germany

Site Status

Praxis Dr. Hirschhäuser

Saarbrücken, , Germany

Site Status

Praxis Dr. Segner, St. Ingbert

Saint Ingbert/Oberwürzbach, , Germany

Site Status

Ambulanzzentrum Schweinfurt

Schweinfurt, , Germany

Site Status

Noordwest Ziekenhuisgroep

Alkmaar, , Netherlands

Site Status

Academisch Medisch Centrum (AMC)

Amsterdam, , Netherlands

Site Status

Rijnstate Hospital

Arnhem, , Netherlands

Site Status

Martini Ziekenhuis

Groningen, , Netherlands

Site Status

Bethesda Ziekenhuis Hoogeveen

Hoogeveen, , Netherlands

Site Status

Sint Franciscus Gasthuis

Rotterdam, , Netherlands

Site Status

Albert Schweitzer Ziekenhuis, Zwijndrecht

Zwijndrecht, , Netherlands

Site Status

Helse Møre og Romsdal HF, Ålesund sjukehus

Ålesund, , Norway

Site Status

Sykehuset Innlandet HF, Avd. Hamar

Hamar, , Norway

Site Status

Akershus Universitetssykehus HF

Lørenskog, , Norway

Site Status

Oslo Universitetssykehus HF, Aker Sykehus

Oslo, , Norway

Site Status

Med Univ Bialystok Clin Dep Endocrinol, Diabetol & Int Dis

Bialystok, , Poland

Site Status

NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny

Bialystok, , Poland

Site Status

Dobry Lekarz,Spec.Med.Clinics,Private Prac,Krakow

Krakow, , Poland

Site Status

NZOZ Specialized Ambulance "MEDICA"

Lublin, , Poland

Site Status

Marcinkowski Poznan Univ of Med Sci, Clin Dept Diab, Poznan

Poznan, , Poland

Site Status

NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom

Radom, , Poland

Site Status

Centrum Medyczne Medyk

Rzeszów, , Poland

Site Status

NBR Polska

Warsaw, , Poland

Site Status

C.A.P. Sardenya

Barcelona, , Spain

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Hospital Vall d'Hebron

Barcelona, , Spain

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Hospital de la Inmaculada Concepción

Granada, , Spain

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Hospital Virgen de la Victoria

Málaga, , Spain

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Hospital General de Segovia

Segovia, , Spain

Site Status

Hospital Nuestra Señora de Valme

Seville, , Spain

Site Status

Hospital Virgen Macarena

Seville, , Spain

Site Status

Ladulaas Kliniska Studier

Borås, , Sweden

Site Status

Centralsjukhuset, Karlstad

Karlstad, , Sweden

Site Status

Läkarhuset, Vällingby

Vällingby, , Sweden

Site Status

Chung Shan Medical University Hospital

Taichung, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

Chi Mei Medical Center

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Tri-Service General Hospital

Taipei, , Taiwan

Site Status

Milton Keynes Hospital

Buckinghamshire, , United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Wellcome Trust Clinical Research Facility

Edinburgh, , United Kingdom

Site Status

Leicester General Hospital

Leicester, , United Kingdom

Site Status

Royal London Hospital

London, , United Kingdom

Site Status

Queen's Medical Centre

Nottingham, , United Kingdom

Site Status

George Eliot Hospital

Nuneaton, , United Kingdom

Site Status

East Surrey Hospital

Surrey, , United Kingdom

Site Status

Queen Elizabeth II Hospital

Welwyn Garden City, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada Czechia Denmark Finland France Germany Netherlands Norway Poland Spain Sweden Taiwan United Kingdom

References

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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

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2014-001922-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1245.69

Identifier Type: -

Identifier Source: org_study_id

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