Clinical trial NCT02414958: Empagliflozin as Adjunctive to InSulin thErapy Over 52 Weeks in Patients With Type 1 Diabetes Mellitus (EASE-2)
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)
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: 2015-04-13
Enrollment: 730
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: 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.


Eligibility criteria: 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

Additional inclusion criteria may apply

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

Additional exclusion criteria may apply

Primary outcomes:
measure: Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 26
timeFrame: Baseline to week 26
measure: 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) )
timeFrame: Baseline to week 26
Secondary outcomes:
measure: Rate Per Patient-year of Investigator-reported Symptomatic Hypoglycaemia 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 Percentage of Time Spent in Target Glucose Range From Weeks 23 to 26
timeFrame: Week 23 to 26
measure: Change From Baseline in Interstitial Glucose Variability Based on the Interquartile Range (IQR) as Determined by CGM in Weeks 23 to 26
timeFrame: Week 23 to 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: Escondido
country: United States
facility: AMCR Institute, Inc.
state: California
city: Huntington Beach
country: United States
facility: Diabetes/Lipid Management and Research Center
state: California
city: Los Angeles
country: United States
facility: National Research Institute
state: California
city: San Mateo
country: United States
facility: Mills-Peninsula Health Services
state: California
city: Tarzana
country: United States
facility: Metabolic Institute of America
state: California
city: Tustin
country: United States
facility: University Clinical Investigators, Inc.
state: California
city: Denver
country: United States
facility: Creekside Endocrine Associates, PC
state: Colorado
city: Fort Lauderdale
country: United States
facility: The Center for Diabetes and Endocrine Care
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute for Research, LLC
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates, PA
state: Florida
city: Lawrenceville
country: United States
facility: Physicians Research Associates, LLC
state: Georgia
city: Roswell
country: United States
facility: Endocrine Research Solutions, Inc.
state: Georgia
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes and Osteoporosis Center
state: Idaho
city: Arlington Heights
country: United States
facility: Northwest Endo Diabetes Research, LLC
state: Illinois
city: Crystal Lake
country: United States
facility: Midwest Endocrinology
state: Illinois
city: West Des Moines
country: United States
facility: Iowa Diabetes and Endocrinology Research Center
state: Iowa
city: Omaha
country: United States
facility: Diabetes anddocrine Associates, PC
state: Nebraska
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: Nashua
country: United States
facility: Southern New Hampshire Diabetes and Endocrinology
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical Center / Albany Medical College
state: New York
city: Staten Island
country: United States
facility: University Physicians Group Research Division
state: New York
city: Morehead City
country: United States
facility: Diabetes and Endocrinology Consultants, PC
state: North Carolina
city: Cincinnati
country: United States
facility: The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital
state: Ohio
city: Nashville
country: United States
facility: Diabetes and Obesity Clinical Trials Center
state: Tennessee
city: Dallas
country: United States
facility: North Texas Endocrine Center
state: Texas
city: Houston
country: United States
facility: Office of Dr. Michelle Zaniewski-Singh
state: Texas
city: Round Rock
country: United States
facility: Texas Diabetes and Endocrinology
state: Texas
city: Salt Lake City
country: United States
facility: Bateman Horne Center
state: Utah
city: South Ogden
country: United States
facility: Advanced Research Institute
state: Utah
city: Federal Way
country: United States
facility: Larry D Stonesifer, MD Inc., PS
state: Washington
city: Renton
country: United States
facility: Rainier Clinical Research Center, Inc
state: Washington
city: Seattle
country: United States
facility: The Polyclinic
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation
state: Washington
city: Coffs Harbour
country: Australia
facility: Coffs Endocrine & Diabetes Services
state: New South Wales
city: Merewether
country: Australia
facility: AIM Centre
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital-Endocrinology
state: Queensland
city: Feldkirch
country: Austria
facility: VIVIT Instit.am LKH Feldkirch,Abt.f.Innere Med.u.Kardiologie
city: Steyr
country: Austria
facility: LKH Steyr, Kardiologie
city: Wien
country: Austria
facility: KH Rudolfstiftung, 1. Med. Abt., Wien
city: Wien
country: Austria
facility: Hospital Hietzing
city: Arlon
country: Belgium
facility: Arlon - HOSP Sud Luxembourg - Vivalia
city: Bonheiden
country: Belgium
facility: Bonheiden - HOSP Imelda
city: Brussel
country: Belgium
facility: Brussels - UNIV UZ Brussel
city: Bruxelles
country: Belgium
facility: ULB Hopital Erasme
city: Edegem
country: Belgium
facility: Edegem - UNIV UZ Antwerpen
city: Gent
country: Belgium
facility: UNIV UZ Gent
city: La Louvière
country: Belgium
facility: La Louvière - UNIV CHU Tivoli
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège
city: Liège
country: Belgium
facility: Liège - HOSP CHR de la Citadelle
city: Merksem
country: Belgium
facility: Merksem - HOSP ZNA Jan Palfijn
city: Calgary
country: Canada
facility: LMC Endocrinology Centres (Calgary) Ltd.
state: Alberta
city: Red Deer
country: Canada
facility: The Bailey Clinic
state: Alberta
city: Victoria
country: Canada
facility: Royal Jubilee Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre Winnipeg
state: Manitoba
city: Montreal
country: Canada
facility: CHUM - Pavillon R
state: Migration Data
city: Halifax
country: Canada
facility: Capital District Health Auth.
state: Nova Scotia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Thornhill
country: Canada
facility: LMC Thornhill/Vaughan
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Praha 2
country: Czechia
facility: General Univ.hosp.in Prague (VFN), Diabetes ambulance
city: Slany
country: Czechia
facility: Diabetology and Internal Practice Dr. Vladimir Lelek
city: Usti nad Labem
country: Czechia
facility: Masaryk Hospital, Internal Department
city: Aalborg
country: Denmark
facility: Aalborg Sygehus Syd
city: Aarhus C
country: Denmark
facility: Aarhus Universitets Hospital
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital - Hillerød
city: Køge
country: Denmark
facility: Køge Sygehus
city: Kuopio
country: Finland
facility: IteLasaretti
city: Oulu
country: Finland
facility: Terveystalo Oulu, Diapolis
city: Turku
country: Finland
facility: TYKS
city: Caen
country: France
facility: HOP Côte de Nacre
city: La Rochelle Cedex 1
country: France
facility: HOP Saint-Louis
city: Narbonne
country: France
facility: HOP de Narbonne, diabéto endo, Narbonne
city: Reims
country: France
facility: HOP Robert Debré
city: Vandoeuvre-lès-Nancy
country: France
facility: HOP de Brabois
city: Vénissieux
country: France
facility: HOP les Portes du Sud, Diabéto, Vénissieux
city: Aschaffenburg
country: Germany
facility: Studienzentrum Aschaffenburg
city: Asslar
country: Germany
facility: Gemeinschaftspraxis, Asslar
city: Berlin
country: Germany
facility: ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH
city: Essen
country: Germany
facility: InnoDiab Forschung GmbH
city: Pirna
country: Germany
facility: Praxis Dr. Kosch, Pirna
city: Rehlingen-Siersburg
country: Germany
facility: Allgemeinmedizinische und Diabetologische Schwerpunktpraxis
city: Saarbrücken
country: Germany
facility: Praxis Dr. Hirschhäuser
city: Saint Ingbert/Oberwürzbach
country: Germany
facility: Praxis Dr. Segner, St. Ingbert
city: Schweinfurt
country: Germany
facility: Ambulanzzentrum Schweinfurt
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum (AMC)
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Hoogeveen
country: Netherlands
facility: Bethesda Ziekenhuis Hoogeveen
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis
city: Zwijndrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, Zwijndrecht
city: Hamar
country: Norway
facility: Sykehuset Innlandet HF, Avd. Hamar
city: Lørenskog
country: Norway
facility: Akershus Universitetssykehus HF
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Aker Sykehus
city: Ålesund
country: Norway
facility: Helse Møre og Romsdal HF, Ålesund sjukehus
city: Bialystok
country: Poland
facility: Med Univ Bialystok Clin Dep Endocrinol, Diabetol & Int Dis
city: Bialystok
country: Poland
facility: NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny
city: Krakow
country: Poland
facility: Dobry Lekarz,Spec.Med.Clinics,Private Prac,Krakow
city: Lublin
country: Poland
facility: NZOZ Specialized Ambulance "MEDICA"
city: Poznan
country: Poland
facility: Marcinkowski Poznan Univ of Med Sci, Clin Dept Diab, Poznan
city: Radom
country: Poland
facility: NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom
city: Rzeszow
country: Poland
facility: Centrum Medyczne Medyk
city: Warsaw
country: Poland
facility: NBR Polska
city: Barcelona
country: Spain
facility: C.A.P. Sardenya
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Granada
country: Spain
facility: Hospital de la Inmaculada Concepción
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Segovia
country: Spain
facility: Hospital General de Segovia
city: Sevilla
country: Spain
facility: Hospital Nuestra Señora de Valme
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Borås
country: Sweden
facility: Ladulaas Kliniska Studier
city: Karlstad
country: Sweden
facility: Centralsjukhuset, Karlstad
city: Vällingby
country: Sweden
facility: Läkarhuset, Vällingby
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Buckinghamshire
country: United Kingdom
facility: Milton Keynes Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Edinburgh
country: United Kingdom
facility: Wellcome Trust Clinical Research Facility
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: London
country: United Kingdom
facility: Royal London Hospital
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
city: Surrey
country: United Kingdom
facility: East Surrey Hospital
city: Welwyn Garden City
country: United Kingdom
facility: Queen Elizabeth II 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.