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

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)

Sponsors

Lead Sponsor: Boehringer Ingelheim

Collaborator: Eli Lilly and Company

Source 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.

Overall Status Completed
Start Date June 30, 2015
Completion Date October 23, 2017
Primary Completion Date April 20, 2017
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 26 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) ) Baseline to week 26
Secondary Outcome
Measure Time Frame
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
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 26 Baseline to week 26
Enrollment 730
Condition
Intervention

Intervention Type: Drug

Intervention Name: Empagliflozin

Arm Group Label: Empagliflozin low dose

Intervention Type: Drug

Intervention Name: Empagliflozin

Arm Group Label: Empagliflozin high dose

Intervention Type: Drug

Intervention Name: Placebo

Arm Group Label: Placebo

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

- 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Boehringer Ingelheim Study Chair Boehringer Ingelheim
Location
Facility:
AMCR Institute, Inc. | Escondido, California, 92025, United States
Diabetes/Lipid Management and Research Center | Huntington Beach, California, 92648, United States
National Research Institute | Los Angeles, California, 90057, United States
Mills-Peninsula Health Services | San Mateo, California, 94401, United States
Metabolic Institute of America | Tarzana, California, 91356, United States
University Clinical Investigators, Inc. | Tustin, California, 92780, United States
Creekside Endocrine Associates, PC | Denver, Colorado, 80246, United States
The Center for Diabetes and Endocrine Care | Fort Lauderdale, Florida, 33312, United States
East Coast Institute for Research, LLC | Jacksonville, Florida, 32204, United States
Baptist Diabetes Associates, PA | Miami, Florida, 33156, United States
Physicians Research Associates, LLC | Lawrenceville, Georgia, 30046, United States
Endocrine Research Solutions, Inc. | Roswell, Georgia, 30076, United States
Rocky Mountain Diabetes and Osteoporosis Center | Idaho Falls, Idaho, 83404, United States
Northwest Endo Diabetes Research, LLC | Arlington Heights, Illinois, 60005, United States
Midwest Endocrinology | Crystal Lake, Illinois, 60012, United States
Iowa Diabetes and Endocrinology Research Center | West Des Moines, Iowa, 50265, United States
Diabetes anddocrine Associates, PC | Omaha, Nebraska, 68114, United States
Desert Endocrinology Clinical Research Center | Henderson, Nevada, 89052, United States
Palm Research Center | Las Vegas, Nevada, 89148, United States
Southern New Hampshire Diabetes and Endocrinology | Nashua, New Hampshire, 03063, United States
Albany Medical Center / Albany Medical College | Albany, New York, 12206, United States
University Physicians Group Research Division | Staten Island, New York, 10301, United States
Diabetes and Endocrinology Consultants, PC | Morehead City, North Carolina, 28557, United States
The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital | Cincinnati, Ohio, 45219, United States
Diabetes and Obesity Clinical Trials Center | Nashville, Tennessee, 37212, United States
North Texas Endocrine Center | Dallas, Texas, 75231, United States
Office of Dr. Michelle Zaniewski-Singh | Houston, Texas, 77090, United States
Texas Diabetes and Endocrinology | Round Rock, Texas, 78681, United States
Bateman Horne Center | Salt Lake City, Utah, 84102, United States
Advanced Research Institute | South Ogden, Utah, 84405, United States
Larry D Stonesifer, MD Inc., PS | Federal Way, Washington, 98003, United States
Rainier Clinical Research Center, Inc | Renton, Washington, 98057, United States
The Polyclinic | Seattle, Washington, 98104, United States
MultiCare Institute for Research and Innovation | Tacoma, Washington, 98405, United States
Coffs Endocrine & Diabetes Services | Coffs Harbour, New South Wales, 2450, Australia
AIM Centre | Merewether, New South Wales, 2291, Australia
Royal Brisbane & Women's Hospital-Endocrinology | Herston, Queensland, 4006, Australia
VIVIT Instit.am LKH Feldkirch,Abt.f.Innere Med.u.Kardiologie | Feldkirch, 6807, Austria
LKH Steyr, Kardiologie | Steyr, 4400, Austria
KH Rudolfstiftung, 1. Med. Abt., Wien | Wien, 1030, Austria
Hospital Hietzing | Wien, 1130, Austria
Arlon - HOSP Sud Luxembourg - Vivalia | Arlon, 6700, Belgium
Bonheiden - HOSP Imelda | Bonheiden, 2820, Belgium
Brussels - UNIV UZ Brussel | Brussel, 1090, Belgium
ULB Hopital Erasme | Bruxelles, 1070, Belgium
Edegem - UNIV UZ Antwerpen | Edegem, 2650, Belgium
UNIV UZ Gent | Gent, 9000, Belgium
La Louvière - UNIV CHU Tivoli | La Louvière, 7100, Belgium
UZ Leuven | Leuven, 3000, Belgium
Centre Hospitalier Universitaire de Liège | Liège, 4000, Belgium
Liège - HOSP CHR de la Citadelle | Liège, 4000, Belgium
Merksem - HOSP ZNA Jan Palfijn | Merksem, 2170, Belgium
LMC Endocrinology Centres (Calgary) Ltd. | Calgary, Alberta, T2H 2G4, Canada
The Bailey Clinic | Red Deer, Alberta, T4N 6V7, Canada
Royal Jubilee Hospital | Victoria, British Columbia, V8R 1J8, Canada
Health Sciences Centre Winnipeg | Winnipeg, Manitoba, R3E 3P4, Canada
CHUM - Pavillon R | Montreal, Migration Data, Quebec, Canada
Capital District Health Auth. | Halifax, Nova Scotia, B3H 1V7, Canada
Kingston General Hospital | Kingston, Ontario, K7L 2V7, Canada
LMC Thornhill/Vaughan | Thornhill, Ontario, L4J 8L7, Canada
Mount Sinai Hospital | Toronto, Ontario, M5T 3L9, Canada
Royal Victoria Hospital | Montreal, Quebec, H3A 1A1, Canada
General Univ.hosp.in Prague (VFN), Diabetes ambulance | Praha 2, 128 08, Czechia
Diabetology and Internal Practice Dr. Vladimir Lelek | Slany, 274 01, Czechia
Masaryk Hospital, Internal Department | Usti nad Labem, 401 13, Czechia
Aalborg Sygehus Syd | Aalborg, 9100, Denmark
Aarhus Universitets Hospital | Aarhus C, 8000, Denmark
Steno Diabetes Center Copenhagen | Gentofte, 2820, Denmark
Nordsjællands Hospital - Hillerød | Hillerød, 3400, Denmark
Køge Sygehus | Køge, 4600, Denmark
IteLasaretti | Kuopio, FI-70100, Finland
Terveystalo Oulu, Diapolis | Oulu, FI-90100, Finland
TYKS | Turku, FI-20520, Finland
HOP Côte de Nacre | Caen, 14033, France
HOP Saint-Louis | La Rochelle Cedex 1, 17000, France
HOP de Narbonne, diabéto endo, Narbonne | Narbonne, 11100, France
HOP Robert Debré | Reims, 51092, France
HOP de Brabois | Vandoeuvre-lès-Nancy, 54511, France
HOP les Portes du Sud, Diabéto, Vénissieux | Vénissieux, 69200, France
Studienzentrum Aschaffenburg | Aschaffenburg, 63739, Germany
Gemeinschaftspraxis, Asslar | Asslar, 35614, Germany
ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH | Berlin, 10115, Germany
InnoDiab Forschung GmbH | Essen, 45136, Germany
Praxis Dr. Kosch, Pirna | Pirna, 01796, Germany
Allgemeinmedizinische und Diabetologische Schwerpunktpraxis | Rehlingen-Siersburg, 66780, Germany
Praxis Dr. Hirschhäuser | Saarbrücken, 66121, Germany
Praxis Dr. Segner, St. Ingbert | Saint Ingbert/Oberwürzbach, 66386, Germany
Ambulanzzentrum Schweinfurt | Schweinfurt, 97421, Germany
Noordwest Ziekenhuisgroep | Alkmaar, 1815 JD, Netherlands
Academisch Medisch Centrum (AMC) | Amsterdam, 1105 AZ, Netherlands
Rijnstate Hospital | Arnhem, 6815 AD, Netherlands
Martini Ziekenhuis | Groningen, 9728 NT, Netherlands
Bethesda Ziekenhuis Hoogeveen | Hoogeveen, 7909 AA, Netherlands
Sint Franciscus Gasthuis | Rotterdam, 3045 PM, Netherlands
Albert Schweitzer Ziekenhuis, Zwijndrecht | Zwijndrecht, 3331 LZ, Netherlands
Sykehuset Innlandet HF, Avd. Hamar | Hamar, N-2318, Norway
Akershus Universitetssykehus HF | Lørenskog, N-1478, Norway
Oslo Universitetssykehus HF, Aker Sykehus | Oslo, N-0424, Norway
Helse Møre og Romsdal HF, Ålesund sjukehus | Ålesund, N-6026, Norway
Med Univ Bialystok Clin Dep Endocrinol, Diabetol & Int Dis | Bialystok, 15-276, Poland
NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny | Bialystok, 15-435, Poland
Dobry Lekarz,Spec.Med.Clinics,Private Prac,Krakow | Krakow, 31011, Poland
NZOZ Specialized Ambulance "MEDICA" | Lublin, 20-538, Poland
Marcinkowski Poznan Univ of Med Sci, Clin Dept Diab, Poznan | Poznan, 60-834, Poland
NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom | Radom, 26610, Poland
Centrum Medyczne Medyk | Rzeszow, 35-055, Poland
NBR Polska | Warsaw, 00-465, Poland
C.A.P. Sardenya | Barcelona, 08025, Spain
Hospital Vall d'Hebron | Barcelona, 08035, Spain
Hospital de la Inmaculada Concepción | Granada, 18004, Spain
Hospital Virgen de la Victoria | Malaga, 29010, Spain
Hospital General de Segovia | Segovia, 40002, Spain
Hospital Nuestra Señora de Valme | Sevilla, 41014, Spain
Hospital Virgen Macarena | Sevilla, 41071, Spain
Ladulaas Kliniska Studier | Borås, 506 30, Sweden
Centralsjukhuset, Karlstad | Karlstad, 651 85, Sweden
Läkarhuset, Vällingby | Vällingby, 162 68, Sweden
Chung Shan Medical University Hospital | Taichung, 402, Taiwan
China Medical University Hospital | Taichung, 40447, Taiwan
Chi Mei Medical Center | Tainan, 710, Taiwan
National Taiwan University Hospital | Taipei, 100, Taiwan
Tri-Service General Hospital | Taipei, 11490, Taiwan
Milton Keynes Hospital | Buckinghamshire, MK65LD, United Kingdom
Addenbrooke's Hospital | Cambridge, CB2 0QQ, United Kingdom
Wellcome Trust Clinical Research Facility | Edinburgh, EH4 2XU, United Kingdom
Leicester General Hospital | Leicester, LE5 4PW, United Kingdom
Royal London Hospital | London, E1 1BB, United Kingdom
Queen's Medical Centre | Nottingham, NG7 2UH, United Kingdom
George Eliot Hospital | Nuneaton, CV10 7DJ, United Kingdom
East Surrey Hospital | Surrey, RH1 5RH, United Kingdom
Queen Elizabeth II Hospital | Welwyn Garden City, AL7 4HQ, United Kingdom
Location Countries

Australia

Austria

Belgium

Canada

Czechia

Denmark

Finland

France

Germany

Netherlands

Norway

Poland

Spain

Sweden

Taiwan

United Kingdom

United States

Verification Date

December 2018

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Empagliflozin low dose

Type: Experimental

Description: Empagliflozin tablets once daily

Label: Empagliflozin high dose

Type: Experimental

Description: Empagliflozin tablets once daily

Label: Placebo

Type: Placebo Comparator

Description: Placebo tablets matching empagliflozin once daily

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double

Source: ClinicalTrials.gov