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Diabetes Mellitus, Type 1Phase 3NCT02414958

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

A Phase 3 study testing Empagliflozin in people with Diabetes Mellitus, Type 1, run by Boehringer Ingelheim at 131 sites in 17 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
Empagliflozin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
730 participants
Where
131 sitesin 17 countries
Study dates
30 Jun 2015to 23 Oct 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Additional inclusion criteria may apply

Who cannot join

  • 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
  • Additional exclusion criteria may apply

Trial locations and contacts

131 sites in 17 countries.

131 sites in 17 countries

United States34 sites

  • Albany Medical Center / Albany Medical College

    Albany, New York, 12206

  • Northwest Endo Diabetes Research, LLC

    Arlington Heights, Illinois, 60005

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

    Cincinnati, Ohio, 45219

  • Midwest Endocrinology

    Crystal Lake, Illinois, 60012

  • North Texas Endocrine Center

    Dallas, Texas, 75231

  • Creekside Endocrine Associates, PC

    Denver, Colorado, 80246

  • AMCR Institute, Inc.

    Escondido, California, 92025

  • Larry D Stonesifer, MD Inc., PS

    Federal Way, Washington, 98003

  • The Center for Diabetes and Endocrine Care

    Fort Lauderdale, Florida, 33312

  • Desert Endocrinology Clinical Research Center

    Henderson, Nevada, 89052

  • Office of Dr. Michelle Zaniewski-Singh

    Houston, Texas, 77090

  • Diabetes/Lipid Management and Research Center

    Huntington Beach, California, 92648

  • Rocky Mountain Diabetes and Osteoporosis Center

    Idaho Falls, Idaho, 83404

  • East Coast Institute for Research, LLC

    Jacksonville, Florida, 32204

  • Palm Research Center

    Las Vegas, Nevada, 89148

  • Physicians Research Associates, LLC

    Lawrenceville, Georgia, 30046

  • National Research Institute

    Los Angeles, California, 90057

  • Baptist Diabetes Associates, PA

    Miami, Florida, 33156

  • Diabetes and Endocrinology Consultants, PC

    Morehead City, North Carolina, 28557

  • Southern New Hampshire Diabetes and Endocrinology

    Nashua, New Hampshire, 03063

  • Diabetes and Obesity Clinical Trials Center

    Nashville, Tennessee, 37212

  • Diabetes anddocrine Associates, PC

    Omaha, Nebraska, 68114

  • Rainier Clinical Research Center, Inc

    Renton, Washington, 98057

  • Endocrine Research Solutions, Inc.

    Roswell, Georgia, 30076

  • Texas Diabetes and Endocrinology

    Round Rock, Texas, 78681

  • Bateman Horne Center

    Salt Lake City, Utah, 84102

  • Mills-Peninsula Health Services

    San Mateo, California, 94401

  • The Polyclinic

    Seattle, Washington, 98104

  • Advanced Research Institute

    South Ogden, Utah, 84405

  • University Physicians Group Research Division

    Staten Island, New York, 10301

  • MultiCare Institute for Research and Innovation

    Tacoma, Washington, 98405

  • Metabolic Institute of America

    Tarzana, California, 91356

  • University Clinical Investigators, Inc.

    Tustin, California, 92780

  • Iowa Diabetes and Endocrinology Research Center

    West Des Moines, Iowa, 50265

Other trials in United States

Belgium11 sites

  • Arlon - HOSP Sud Luxembourg - Vivalia

    Arlon, 6700

  • Bonheiden - HOSP Imelda

    Bonheiden, 2820

  • ULB Hopital Erasme

    Brussels, 1070

  • Brussels - UNIV UZ Brussel

    Brussels, 1090

  • Edegem - UNIV UZ Antwerpen

    Edegem, 2650

  • UNIV UZ Gent

    Ghent, 9000

  • La Louvière - UNIV CHU Tivoli

    La Louvière, 7100

  • UZ Leuven

    Leuven, 3000

  • Centre Hospitalier Universitaire de Liège

    Liège, 4000

  • Liège - HOSP CHR de la Citadelle

    Liège, 4000

  • Merksem - HOSP ZNA Jan Palfijn

    Merksem, 2170

Other trials in Belgium

Canada10 sites

  • LMC Endocrinology Centres (Calgary) Ltd.

    Calgary, Alberta, T2H 2G4

  • Capital District Health Auth.

    Halifax, Nova Scotia, B3H 1V7

  • Kingston General Hospital

    Kingston, Ontario, K7L 2V7

  • CHUM - Pavillon R

    Montreal, Migration Data, Quebec

  • Royal Victoria Hospital

    Montreal, Quebec, H3A 1A1

  • The Bailey Clinic

    Red Deer, Alberta, T4N 6V7

  • LMC Thornhill/Vaughan

    Thornhill, Ontario, L4J 8L7

  • Mount Sinai Hospital

    Toronto, Ontario, M5T 3L9

  • Royal Jubilee Hospital

    Victoria, British Columbia, V8R 1J8

  • Health Sciences Centre Winnipeg

    Winnipeg, Manitoba, R3E 3P4

Other trials in Canada

Germany9 sites

  • Studienzentrum Aschaffenburg

    Aschaffenburg, 63739

  • Gemeinschaftspraxis, Asslar

    Aßlar, 35614

  • ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH

    Berlin, 10115

  • InnoDiab Forschung GmbH

    Essen, 45136

  • Praxis Dr. Kosch, Pirna

    Pirna, 01796

  • Allgemeinmedizinische und Diabetologische Schwerpunktpraxis

    Rehlingen-Siersburg, 66780

  • Praxis Dr. Hirschhäuser

    Saarbrücken, 66121

  • Praxis Dr. Segner, St. Ingbert

    Saint Ingbert/Oberwürzbach, 66386

  • Ambulanzzentrum Schweinfurt

    Schweinfurt, 97421

Other trials in Germany

United Kingdom9 sites

  • Milton Keynes Hospital

    Buckinghamshire, MK65LD

  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

  • Wellcome Trust Clinical Research Facility

    Edinburgh, EH4 2XU

  • Leicester General Hospital

    Leicester, LE5 4PW

  • Royal London Hospital

    London, E1 1BB

  • Queen's Medical Centre

    Nottingham, NG7 2UH

  • George Eliot Hospital

    Nuneaton, CV10 7DJ

  • East Surrey Hospital

    Surrey, RH1 5RH

  • Queen Elizabeth II Hospital

    Welwyn Garden City, AL7 4HQ

Other trials in United Kingdom

Poland8 sites

  • Med Univ Bialystok Clin Dep Endocrinol, Diabetol & Int Dis

    Bialystok, 15-276

  • NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny

    Bialystok, 15-435

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

    Krakow, 31011

  • NZOZ Specialized Ambulance "MEDICA"

    Lublin, 20-538

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

    Poznan, 60-834

  • NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom

    Radom, 26610

  • Centrum Medyczne Medyk

    Rzeszów, 35-055

  • NBR Polska

    Warsaw, 00-465

Other trials in Poland

Netherlands7 sites

  • Noordwest Ziekenhuisgroep

    Alkmaar, 1815 JD

  • Academisch Medisch Centrum (AMC)

    Amsterdam, 1105 AZ

  • Rijnstate Hospital

    Arnhem, 6815 AD

  • Martini Ziekenhuis

    Groningen, 9728 NT

  • Bethesda Ziekenhuis Hoogeveen

    Hoogeveen, 7909 AA

  • Sint Franciscus Gasthuis

    Rotterdam, 3045 PM

  • Albert Schweitzer Ziekenhuis, Zwijndrecht

    Zwijndrecht, 3331 LZ

Other trials in Netherlands

Spain7 sites

  • C.A.P. Sardenya

    Barcelona, 08025

  • Hospital Vall d'Hebron

    Barcelona, 08035

  • Hospital de la Inmaculada Concepción

    Granada, 18004

  • Hospital Virgen de la Victoria

    Málaga, 29010

  • Hospital General de Segovia

    Segovia, 40002

  • Hospital Nuestra Señora de Valme

    Seville, 41014

  • Hospital Virgen Macarena

    Seville, 41071

Other trials in Spain

France6 sites

  • HOP Côte de Nacre

    Caen, 14033

  • HOP Saint-Louis

    La Rochelle, 17000

  • HOP de Narbonne, diabéto endo, Narbonne

    Narbonne, 11100

  • HOP Robert Debré

    Reims, 51092

  • HOP de Brabois

    Vandœuvre-lès-Nancy, 54511

  • HOP les Portes du Sud, Diabéto, Vénissieux

    Vénissieux, 69200

Other trials in France

Denmark5 sites

  • Aalborg Sygehus Syd

    Aalborg, 9100

  • Aarhus Universitets Hospital

    Aarhus C, 8000

  • Steno Diabetes Center Copenhagen

    Gentofte Municipality, 2820

  • Nordsjællands Hospital - Hillerød

    Hillerød, 3400

  • Køge Sygehus

    Køge, 4600

Other trials in Denmark

Taiwan5 sites

  • Chung Shan Medical University Hospital

    Taichung, 402

  • China Medical University Hospital

    Taichung, 40447

  • Chi Mei Medical Center

    Tainan, 710

  • National Taiwan University Hospital

    Taipei, 100

  • Tri-Service General Hospital

    Taipei, 11490

Other trials in Taiwan

Austria4 sites

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

    Feldkirch, 6807

  • LKH Steyr, Kardiologie

    Steyr, 4400

  • KH Rudolfstiftung, 1. Med. Abt., Wien

    Vienna, 1030

  • Hospital Hietzing

    Vienna, 1130

Other trials in Austria

Norway4 sites

  • Helse Møre og Romsdal HF, Ålesund sjukehus

    Ålesund, N-6026

  • Sykehuset Innlandet HF, Avd. Hamar

    Hamar, N-2318

  • Akershus Universitetssykehus HF

    Lørenskog, N-1478

  • Oslo Universitetssykehus HF, Aker Sykehus

    Oslo, N-0424

Other trials in Norway

Australia3 sites

  • Coffs Endocrine & Diabetes Services

    Coffs Harbour, New South Wales, 2450

  • Royal Brisbane & Women's Hospital-Endocrinology

    Herston, Queensland, 4006

  • AIM Centre

    Merewether, New South Wales, 2291

Other trials in Australia

Czechia3 sites

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

    Prague, 128 08

  • Diabetology and Internal Practice Dr. Vladimir Lelek

    Slaný, 274 01

  • Masaryk Hospital, Internal Department

    Ústí nad Labem, 401 13

Other trials in Czechia

Finland3 sites

  • IteLasaretti

    Kuopio, FI-70100

  • Terveystalo Oulu, Diapolis

    Oulu, FI-90100

  • TYKS

    Turku, FI-20520

Other trials in Finland

Sweden3 sites

  • Ladulaas Kliniska Studier

    Borås, 506 30

  • Centralsjukhuset, Karlstad

    Karlstad, 651 85

  • Läkarhuset, Vällingby

    Vällingby, 162 68

Other trials in Sweden

About this study

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 52 Weeks in Patients With Type 1 Diabetes Mellitus (EASE-2)

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.

Being tested
Empagliflozin, Placebo
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02414958
Study groupRoleWhat they receive
Empagliflozin low doseExperimentalEmpagliflozin tablets once daily
Receives: Drug: Empagliflozin
Empagliflozin high doseExperimentalEmpagliflozin tablets once daily
Receives: Drug: Empagliflozin
PlaceboPlacebo comparatorPlacebo tablets matching empagliflozin once daily
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to week 26

  2. 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.

    Measured: Baseline to week 26

Secondary outcomes (6)

  1. Rate Per Patient-year of Investigator-reported Symptomatic Hypoglycaemia Adverse Events (AEs) With Confirmed Plasma Glucose (PG)

    This is a key secondary endpoint. Rate per patient-year of investigator-reported symptomatic hypoglycaemia adverse events (AEs) with confirmed plasma glucose (PG) <54 milligram per deciliter (mg/dL) (<3.0 millimoles per litre (mmol/L)) and/or severe hypoglycaemia AEs (i.e. all investigator-reported AEs that had confirmed PG <54 mg/dL [<3.0 mmol/L] with symptoms reported and all severe hypoglycaemia 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.

    Measured: Week 5 to Week 26, Week 1 to Week 26

  2. 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 randomised trial medication. Least squares mean is adjusted mean change from baseline.

    Measured: Baseline to week 26

  3. Change From Baseline in Percentage of Time Spent in Target Glucose Range From Weeks 23 to 26

    Change from baseline in the percentage of time spent in target glucose range of >70 to ≤180 mg/dL (>3.9 to ≤10.0 mmol/L) as determined by continuous glucose monitoring (CGM) is presented in week 23 to 26. Least squares mean is actually an adjusted event rate.

    Measured: Week 23 to 26

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

    Change from baseline in interstitial glucose variability based on the IQR as determined by CGM is presented for week 23 to 26. Least squares mean is actually an adjusted event rate.

    Measured: Week 23 to 26

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

    Change from baseline in TDID 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.

    Measured: Baseline to week 26

  6. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 26

    Change from baseline in SBP and DBP 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.

    Measured: Baseline to week 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2015 (estimated)
  2. Study start30 Jun 2015
  3. Primary completion20 Apr 2017
  4. Study completion23 Oct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Enrolment
730 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02414958
Sponsor's protocol ID
1245.69
Other IDs
2014-001922-14, 2014
Status last verified
Dec 2018
First submitted
8 Apr 2015
Last updated
3 Jan 2019

Publications

  • 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.

    PubMed 37616393

  • 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.

    PubMed 30287422

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Empagliflozin in people with Diabetes Mellitus, Type 1, run by Boehringer Ingelheim at 131 sites in 17 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 131 sites in United States, Belgium, Canada, Germany, United Kingdom and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 26 (time frame: Baseline to week 26). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02414958, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2019.

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