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

NCT02414958 | Completed Phase 3 Results

• 2 other identifiers: 1245.692014-001922-14
• Study Type: interventional
• Target: 730
• Locations: 16 countries
• Sites: 127

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 26

  Change from baseline in glycated haemoglobin (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 randomised trial medication. Least squares mean is adjusted mean change from baseline. Restricted maximum likelihood estimation based on mixed-effect model for repeated measures (MMRM) analysis was used to obtain adjusted means for the treatment effects.

  Baseline to week 26

• Change From Baseline in Glycated Haemoglobin (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 haemoglobin (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 randomised trial medication. Least squares mean is adjusted mean change from baseline. Restricted maximum likelihood estimation based on mixed-effect model for repeated measures (MMRM) analysis was used to obtain adjusted means for the treatment effects.

  Baseline to week 26

Secondary Outcomes (6)

• Rate Per Patient-year of Investigator-reported Symptomatic Hypoglycaemia 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 Percentage of Time Spent in Target Glucose Range From Weeks 23 to 26

  Week 23 to 26

• Change From Baseline in Interstitial Glucose Variability Based on the Interquartile Range (IQR) as Determined by CGM in Weeks 23 to 26

  Week 23 to 26

• Change From Baseline in Total Daily Insulin Dose (TDID) at Week 26

  Baseline to week 26

Study Arms (3)

Empagliflozin low dose

EXPERIMENTAL

Empagliflozin tablets once daily

Drug: Empagliflozin

Empagliflozin high dose

EXPERIMENTAL

Empagliflozin tablets once daily

Drug: Empagliflozin

Placebo

PLACEBO COMPARATOR

Placebo tablets matching empagliflozin once daily

Drug: Placebo

Interventions

Empagliflozin DRUG

Empagliflozin low dose

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Eli Lilly and Company: collaborator

Study Sites (131)

AMCR Institute, Inc.

Escondido, California, 92025, United States

Location

Diabetes/Lipid Management and Research Center

Huntington Beach, California, 92648, United States

Location

National Research Institute

Los Angeles, California, 90057, United States

Location

Mills-Peninsula Health Services

San Mateo, California, 94401, United States

Location

Metabolic Institute of America

Tarzana, California, 91356, United States

Location

University Clinical Investigators, Inc.

Tustin, California, 92780, United States

Location

Creekside Endocrine Associates, PC

Denver, Colorado, 80246, United States

Location

The Center for Diabetes and Endocrine Care

Fort Lauderdale, Florida, 33312, United States

Location

East Coast Institute for Research, LLC

Jacksonville, Florida, 32204, United States

Location

Baptist Diabetes Associates, PA

Miami, Florida, 33156, United States

Location

Physicians Research Associates, LLC

Lawrenceville, Georgia, 30046, United States

Location

Endocrine Research Solutions, Inc.

Roswell, Georgia, 30076, United States

Location

Rocky Mountain Diabetes and Osteoporosis Center

Idaho Falls, Idaho, 83404, United States

Location

Northwest Endo Diabetes Research, LLC

Arlington Heights, Illinois, 60005, United States

Location

Midwest Endocrinology

Crystal Lake, Illinois, 60012, United States

Location

Iowa Diabetes and Endocrinology Research Center

West Des Moines, Iowa, 50265, United States

Location

Diabetes anddocrine Associates, PC

Omaha, Nebraska, 68114, United States

Location

Desert Endocrinology Clinical Research Center

Henderson, Nevada, 89052, United States

Location

Palm Research Center

Las Vegas, Nevada, 89148, United States

Location

Southern New Hampshire Diabetes and Endocrinology

Nashua, New Hampshire, 03063, United States

Location

Albany Medical Center / Albany Medical College

Albany, New York, 12206, United States

Location

University Physicians Group Research Division

Staten Island, New York, 10301, United States

Location

Diabetes and Endocrinology Consultants, PC

Morehead City, North Carolina, 28557, United States

Location

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

Cincinnati, Ohio, 45219, United States

Location

Diabetes and Obesity Clinical Trials Center

Nashville, Tennessee, 37212, United States

Location

North Texas Endocrine Center

Dallas, Texas, 75231, United States

Location

Office of Dr. Michelle Zaniewski-Singh

Houston, Texas, 77090, United States

Location

Texas Diabetes and Endocrinology

Round Rock, Texas, 78681, United States

Location

Bateman Horne Center

Salt Lake City, Utah, 84102, United States

Location

Advanced Research Institute

South Ogden, Utah, 84405, United States

Location

Larry D Stonesifer, MD Inc., PS

Federal Way, Washington, 98003, United States

Location

Rainier Clinical Research Center, Inc

Renton, Washington, 98057, United States

Location

The Polyclinic

Seattle, Washington, 98104, United States

Location

MultiCare Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

Coffs Endocrine & Diabetes Services

Coffs Harbour, New South Wales, 2450, Australia

Location

AIM Centre

Merewether, New South Wales, 2291, Australia

Location

Royal Brisbane & Women's Hospital-Endocrinology

Herston, Queensland, 4006, Australia

Location

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

Feldkirch, 6807, Austria

Location

LKH Steyr, Kardiologie

Steyr, 4400, Austria

Location

KH Rudolfstiftung, 1. Med. Abt., Wien

Vienna, 1030, Austria

Location

Hospital Hietzing

Vienna, 1130, Austria

Location

Arlon - HOSP Sud Luxembourg - Vivalia

Arlon, 6700, Belgium

Location

Bonheiden - HOSP Imelda

Bonheiden, 2820, Belgium

Location

ULB Hopital Erasme

Brussels, 1070, Belgium

Location

Brussels - UNIV UZ Brussel

Brussels, 1090, Belgium

Location

Edegem - UNIV UZ Antwerpen

Edegem, 2650, Belgium

Location

UNIV UZ Gent

Ghent, 9000, Belgium

Location

La Louvière - UNIV CHU Tivoli

La Louvière, 7100, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, 4000, Belgium

Location

Liège - HOSP CHR de la Citadelle

Liège, 4000, Belgium

Location

Merksem - HOSP ZNA Jan Palfijn

Merksem, 2170, Belgium

Location

LMC Endocrinology Centres (Calgary) Ltd.

Calgary, Alberta, T2H 2G4, Canada

Location

The Bailey Clinic

Red Deer, Alberta, T4N 6V7, Canada

Location

Royal Jubilee Hospital

Victoria, British Columbia, V8R 1J8, Canada

Location

Health Sciences Centre Winnipeg

Winnipeg, Manitoba, R3E 3P4, Canada

Location

CHUM - Pavillon R

Montreal, Migration Data, Quebec, Canada

Location

Capital District Health Auth.

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

LMC Thornhill/Vaughan

Thornhill, Ontario, L4J 8L7, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5T 3L9, Canada

Location

Royal Victoria Hospital

Montreal, Quebec, H3A 1A1, Canada

Location

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

Prague, 128 08, Czechia

Location

Diabetology and Internal Practice Dr. Vladimir Lelek

Slaný, 274 01, Czechia

Location

Masaryk Hospital, Internal Department

Ústí nad Labem, 401 13, Czechia

Location

Aalborg Sygehus Syd

Aalborg, 9100, Denmark

Location

Aarhus Universitets Hospital

Aarhus C, 8000, Denmark

Location

Steno Diabetes Center Copenhagen

Gentofte Municipality, 2820, Denmark

Location

Nordsjællands Hospital - Hillerød

Hillerød, 3400, Denmark

Location

Køge Sygehus

Køge, 4600, Denmark

Location

IteLasaretti

Kuopio, FI-70100, Finland

Location

Terveystalo Oulu, Diapolis

Oulu, FI-90100, Finland

Location

TYKS

Turku, FI-20520, Finland

Location

HOP Côte de Nacre

Caen, 14033, France

Location

HOP Saint-Louis

La Rochelle, 17000, France

Location

HOP de Narbonne, diabéto endo, Narbonne

Narbonne, 11100, France

Location

HOP Robert Debré

Reims, 51092, France

Location

HOP de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

HOP les Portes du Sud, Diabéto, Vénissieux

Vénissieux, 69200, France

Location

Studienzentrum Aschaffenburg

Aschaffenburg, 63739, Germany

Location

Gemeinschaftspraxis, Asslar

Aßlar, 35614, Germany

Location

ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH

Berlin, 10115, Germany

Location

InnoDiab Forschung GmbH

Essen, 45136, Germany

Location

Praxis Dr. Kosch, Pirna

Pirna, 01796, Germany

Location

Allgemeinmedizinische und Diabetologische Schwerpunktpraxis

Rehlingen-Siersburg, 66780, Germany

Location

Praxis Dr. Hirschhäuser

Saarbrücken, 66121, Germany

Location

Praxis Dr. Segner, St. Ingbert

Saint Ingbert/Oberwürzbach, 66386, Germany

Location

Ambulanzzentrum Schweinfurt

Schweinfurt, 97421, Germany

Location

Noordwest Ziekenhuisgroep

Alkmaar, 1815 JD, Netherlands

Location

Academisch Medisch Centrum (AMC)

Amsterdam, 1105 AZ, Netherlands

Location

Rijnstate Hospital

Arnhem, 6815 AD, Netherlands

Location

Martini Ziekenhuis

Groningen, 9728 NT, Netherlands

Location

Bethesda Ziekenhuis Hoogeveen

Hoogeveen, 7909 AA, Netherlands

Location

Sint Franciscus Gasthuis

Rotterdam, 3045 PM, Netherlands

Location

Albert Schweitzer Ziekenhuis, Zwijndrecht

Zwijndrecht, 3331 LZ, Netherlands

Location

Helse Møre og Romsdal HF, Ålesund sjukehus

Ålesund, N-6026, Norway

Location

Sykehuset Innlandet HF, Avd. Hamar

Hamar, N-2318, Norway

Location

Akershus Universitetssykehus HF

Lørenskog, N-1478, Norway

Location

Oslo Universitetssykehus HF, Aker Sykehus

Oslo, N-0424, Norway

Location

Med Univ Bialystok Clin Dep Endocrinol, Diabetol & Int Dis

Bialystok, 15-276, Poland

Location

NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny

Bialystok, 15-435, Poland

Location

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

Krakow, 31011, Poland

Location

NZOZ Specialized Ambulance "MEDICA"

Lublin, 20-538, Poland

Location

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

Poznan, 60-834, Poland

Location

NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom

Radom, 26610, Poland

Location

Centrum Medyczne Medyk

Rzeszów, 35-055, Poland

Location

NBR Polska

Warsaw, 00-465, Poland

Location

C.A.P. Sardenya

Barcelona, 08025, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de la Inmaculada Concepción

Granada, 18004, Spain

Location

Hospital Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital General de Segovia

Segovia, 40002, Spain

Location

Hospital Nuestra Señora de Valme

Seville, 41014, Spain

Location

Hospital Virgen Macarena

Seville, 41071, Spain

Location

Ladulaas Kliniska Studier

Borås, 506 30, Sweden

Location

Centralsjukhuset, Karlstad

Karlstad, 651 85, Sweden

Location

Läkarhuset, Vällingby

Vällingby, 162 68, Sweden

Location

Chung Shan Medical University Hospital

Taichung, 402, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Chi Mei Medical Center

Tainan, 710, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Milton Keynes Hospital

Buckinghamshire, MK65LD, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Wellcome Trust Clinical Research Facility

Edinburgh, EH4 2XU, United Kingdom

Location

Leicester General Hospital

Leicester, LE5 4PW, United Kingdom

Location

Royal London Hospital

London, E1 1BB, United Kingdom

Location

Queen's Medical Centre

Nottingham, NG7 2UH, United Kingdom

Location

George Eliot Hospital

Nuneaton, CV10 7DJ, United Kingdom

Location

East Surrey Hospital

Surrey, RH1 5RH, United Kingdom

Location

Queen Elizabeth II Hospital

Welwyn Garden City, AL7 4HQ, United Kingdom

Location

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: 37616393 DERIVED

• 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.

  PMID: 30287422 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

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: April 8, 2015
• First Posted: April 13, 2015
• Study Start: June 30, 2015
• Primary Completion: April 20, 2017
• Study Completion: October 23, 2017
• Last Updated: January 3, 2019
• Results First Posted: November 20, 2018

Record last verified: 2018-12

Locations

FR (6); DE (9); FI (3); TW (5); CZ (3); ES (7); AU (3); US (34); CA (10); BE (11); DK (5); NL (7); SE (3); NO (4); GB (9); PL (8)