Empagliflozin as Adjunctive to InSulin thErapy Over 52 Weeks in Patients With Type 1 Diabetes Mellitus (EASE-2)
- Registration Number
- NCT02414958
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 730
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Empagliflozin low dose Empagliflozin Empagliflozin tablets once daily Placebo Placebo Placebo tablets matching empagliflozin once daily Empagliflozin high dose Empagliflozin Empagliflozin tablets once daily
- Primary Outcome Measures
Name Time Method Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 26 Baseline to 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.
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) ) Baseline to week 26 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.
- Secondary Outcome Measures
Name Time Method 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 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.
Change From Baseline in Total Daily Insulin Dose (TDID) at Week 26 Baseline to 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.
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 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.
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 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.
Change From Baseline in Body Weight at Week 26 Baseline to 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.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 26 Baseline to 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.
Trial Locations
- Locations (131)
Rocky Mountain Diabetes and Osteoporosis Center
🇺🇸Idaho Falls, Idaho, United States
Northwest Endo Diabetes Research, LLC
🇺🇸Arlington Heights, Illinois, United States
Office of Dr. Michelle Zaniewski-Singh
🇺🇸Houston, Texas, United States
Health Sciences Centre Winnipeg
🇨🇦Winnipeg, Manitoba, Canada
IteLasaretti
🇫🇮Kuopio, Finland
KH Rudolfstiftung, 1. Med. Abt., Wien
🇦🇹Wien, Austria
Hospital Hietzing
🇦🇹Wien, Austria
Diabetes and Obesity Clinical Trials Center
🇺🇸Nashville, Tennessee, United States
Brussels - UNIV UZ Brussel
🇧🇪Brussel, Belgium
Edegem - UNIV UZ Antwerpen
🇧🇪Edegem, Belgium
LMC Endocrinology Centres (Calgary) Ltd.
🇨🇦Calgary, Alberta, Canada
UZ Leuven
🇧🇪Leuven, Belgium
Palm Research Center
🇺🇸Las Vegas, Nevada, United States
Advanced Research Institute
🇺🇸South Ogden, Utah, United States
Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Diabetes anddocrine Associates, PC
🇺🇸Omaha, Nebraska, United States
Merksem - HOSP ZNA Jan Palfijn
🇧🇪Merksem, Belgium
CHUM - Pavillon R
🇨🇦Montreal, Migration Data, Canada
HOP Saint-Louis
🇫🇷La Rochelle Cedex 1, France
Praxis Dr. Kosch, Pirna
🇩🇪Pirna, Germany
Bonheiden - HOSP Imelda
🇧🇪Bonheiden, Belgium
ULB Hopital Erasme
🇧🇪Bruxelles, Belgium
UNIV UZ Gent
🇧🇪Gent, Belgium
Centre Hospitalier Universitaire de Liège
🇧🇪Liège, Belgium
Royal Brisbane & Women's Hospital-Endocrinology
🇦🇺Herston, Queensland, Australia
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Arlon - HOSP Sud Luxembourg - Vivalia
🇧🇪Arlon, Belgium
Allgemeinmedizinische und Diabetologische Schwerpunktpraxis
🇩🇪Rehlingen-Siersburg, Germany
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Nordsjællands Hospital - Hillerød
🇩🇰Hillerød, Denmark
National Research Institute
🇺🇸Los Angeles, California, United States
Baptist Diabetes Associates, PA
🇺🇸Miami, Florida, United States
The Center for Diabetes and Endocrine Care
🇺🇸Fort Lauderdale, Florida, United States
AMCR Institute, Inc.
🇺🇸Escondido, California, United States
Diabetes/Lipid Management and Research Center
🇺🇸Huntington Beach, California, United States
Creekside Endocrine Associates, PC
🇺🇸Denver, Colorado, United States
Mills-Peninsula Health Services
🇺🇸San Mateo, California, United States
Endocrine Research Solutions, Inc.
🇺🇸Roswell, Georgia, United States
Southern New Hampshire Diabetes and Endocrinology
🇺🇸Nashua, New Hampshire, United States
Diabetes and Endocrinology Consultants, PC
🇺🇸Morehead City, North Carolina, United States
Desert Endocrinology Clinical Research Center
🇺🇸Henderson, Nevada, United States
University Physicians Group Research Division
🇺🇸Staten Island, New York, United States
LKH Steyr, Kardiologie
🇦🇹Steyr, Austria
La Louvière - UNIV CHU Tivoli
🇧🇪La Louvière, Belgium
Liège - HOSP CHR de la Citadelle
🇧🇪Liège, Belgium
The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
VIVIT Instit.am LKH Feldkirch,Abt.f.Innere Med.u.Kardiologie
🇦🇹Feldkirch, Austria
MultiCare Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
The Bailey Clinic
🇨🇦Red Deer, Alberta, Canada
HOP Côte de Nacre
🇫🇷Caen, France
Masaryk Hospital, Internal Department
🇨🇿Usti nad Labem, Czechia
Terveystalo Oulu, Diapolis
🇫🇮Oulu, Finland
TYKS
🇫🇮Turku, Finland
HOP Robert Debré
🇫🇷Reims, France
HOP les Portes du Sud, Diabéto, Vénissieux
🇫🇷Vénissieux, France
Køge Sygehus
🇩🇰Køge, Denmark
Praxis Dr. Hirschhäuser
🇩🇪Saarbrücken, Germany
ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH
🇩🇪Berlin, Germany
HOP de Brabois
🇫🇷Vandoeuvre-lès-Nancy, France
Gemeinschaftspraxis, Asslar
🇩🇪Asslar, Germany
Studienzentrum Aschaffenburg
🇩🇪Aschaffenburg, Germany
Ambulanzzentrum Schweinfurt
🇩🇪Schweinfurt, Germany
Sint Franciscus Gasthuis
🇳🇱Rotterdam, Netherlands
Albert Schweitzer Ziekenhuis, Zwijndrecht
🇳🇱Zwijndrecht, Netherlands
Sykehuset Innlandet HF, Avd. Hamar
🇳🇴Hamar, Norway
Akershus Universitetssykehus HF
🇳🇴Lørenskog, Norway
InnoDiab Forschung GmbH
🇩🇪Essen, Germany
Noordwest Ziekenhuisgroep
🇳🇱Alkmaar, Netherlands
Martini Ziekenhuis
🇳🇱Groningen, Netherlands
Academisch Medisch Centrum (AMC)
🇳🇱Amsterdam, Netherlands
Helse Møre og Romsdal HF, Ålesund sjukehus
🇳🇴Ålesund, Norway
Oslo Universitetssykehus HF, Aker Sykehus
🇳🇴Oslo, Norway
Med Univ Bialystok Clin Dep Endocrinol, Diabetol & Int Dis
🇵🇱Bialystok, Poland
Centrum Medyczne Medyk
🇵🇱Rzeszow, Poland
NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny
🇵🇱Bialystok, Poland
NZOZ Specialized Ambulance "MEDICA"
🇵🇱Lublin, Poland
Marcinkowski Poznan Univ of Med Sci, Clin Dept Diab, Poznan
🇵🇱Poznan, Poland
Dobry Lekarz,Spec.Med.Clinics,Private Prac,Krakow
🇵🇱Krakow, Poland
C.A.P. Sardenya
🇪🇸Barcelona, Spain
NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom
🇵🇱Radom, Poland
NBR Polska
🇵🇱Warsaw, Poland
Chung Shan Medical University Hospital
🇨🇳Taichung, Taiwan
Ladulaas Kliniska Studier
🇸🇪Borås, Sweden
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital de la Inmaculada Concepción
🇪🇸Granada, Spain
Hospital General de Segovia
🇪🇸Segovia, Spain
Hospital Nuestra Señora de Valme
🇪🇸Sevilla, Spain
Chi Mei Medical Center
🇨🇳Tainan, Taiwan
East Surrey Hospital
🇬🇧Surrey, United Kingdom
Queen Elizabeth II Hospital
🇬🇧Welwyn Garden City, United Kingdom
Milton Keynes Hospital
🇬🇧Buckinghamshire, United Kingdom
Hospital Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Virgen Macarena
🇪🇸Sevilla, Spain
University Clinical Investigators, Inc.
🇺🇸Tustin, California, United States
North Texas Endocrine Center
🇺🇸Dallas, Texas, United States
Physicians Research Associates, LLC
🇺🇸Lawrenceville, Georgia, United States
Larry D Stonesifer, MD Inc., PS
🇺🇸Federal Way, Washington, United States
Rainier Clinical Research Center, Inc
🇺🇸Renton, Washington, United States
Capital District Health Auth.
🇨🇦Halifax, Nova Scotia, Canada
Metabolic Institute of America
🇺🇸Tarzana, California, United States
Iowa Diabetes and Endocrinology Research Center
🇺🇸West Des Moines, Iowa, United States
Albany Medical Center / Albany Medical College
🇺🇸Albany, New York, United States
Midwest Endocrinology
🇺🇸Crystal Lake, Illinois, United States
Texas Diabetes and Endocrinology
🇺🇸Round Rock, Texas, United States
AIM Centre
🇦🇺Merewether, New South Wales, Australia
Coffs Endocrine & Diabetes Services
🇦🇺Coffs Harbour, New South Wales, Australia
The Polyclinic
🇺🇸Seattle, Washington, United States
LMC Thornhill/Vaughan
🇨🇦Thornhill, Ontario, Canada
Diabetology and Internal Practice Dr. Vladimir Lelek
🇨🇿Slany, Czechia
Royal Jubilee Hospital
🇨🇦Victoria, British Columbia, Canada
Aarhus Universitets Hospital
🇩🇰Aarhus C, Denmark
General Univ.hosp.in Prague (VFN), Diabetes ambulance
🇨🇿Praha 2, Czechia
Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
Aalborg Sygehus Syd
🇩🇰Aalborg, Denmark
Steno Diabetes Center Copenhagen
🇩🇰Gentofte, Denmark
HOP de Narbonne, diabéto endo, Narbonne
🇫🇷Narbonne, France
Praxis Dr. Segner, St. Ingbert
🇩🇪Saint Ingbert/Oberwürzbach, Germany
Rijnstate Hospital
🇳🇱Arnhem, Netherlands
Bethesda Ziekenhuis Hoogeveen
🇳🇱Hoogeveen, Netherlands
Centralsjukhuset, Karlstad
🇸🇪Karlstad, Sweden
Läkarhuset, Vällingby
🇸🇪Vällingby, Sweden
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Leicester General Hospital
🇬🇧Leicester, United Kingdom
Queen's Medical Centre
🇬🇧Nottingham, United Kingdom
Wellcome Trust Clinical Research Facility
🇬🇧Edinburgh, United Kingdom
George Eliot Hospital
🇬🇧Nuneaton, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom
East Coast Institute for Research, LLC
🇺🇸Jacksonville, Florida, United States
Bateman Horne Center
🇺🇸Salt Lake City, Utah, United States