Diabetes Mellitus, Type 1 Clinical Trial
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)
Verified date | December 2018 |
Source | Boehringer Ingelheim |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 730 |
Est. completion date | October 23, 2017 |
Est. primary completion date | April 20, 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
Australia | Coffs Endocrine & Diabetes Services | Coffs Harbour | New South Wales |
Australia | Royal Brisbane & Women's Hospital-Endocrinology | Herston | Queensland |
Australia | AIM Centre | Merewether | New South Wales |
Austria | VIVIT Instit.am LKH Feldkirch,Abt.f.Innere Med.u.Kardiologie | Feldkirch | |
Austria | LKH Steyr, Kardiologie | Steyr | |
Austria | Hospital Hietzing | Wien | |
Austria | KH Rudolfstiftung, 1. Med. Abt., Wien | Wien | |
Belgium | Arlon - HOSP Sud Luxembourg - Vivalia | Arlon | |
Belgium | Bonheiden - HOSP Imelda | Bonheiden | |
Belgium | Brussels - UNIV UZ Brussel | Brussel | |
Belgium | ULB Hopital Erasme | Bruxelles | |
Belgium | Edegem - UNIV UZ Antwerpen | Edegem | |
Belgium | UNIV UZ Gent | Gent | |
Belgium | La Louvière - UNIV CHU Tivoli | La Louvière | |
Belgium | UZ Leuven | Leuven | |
Belgium | Centre Hospitalier Universitaire de Liège | Liège | |
Belgium | Liège - HOSP CHR de la Citadelle | Liège | |
Belgium | Merksem - HOSP ZNA Jan Palfijn | Merksem | |
Canada | LMC Endocrinology Centres (Calgary) Ltd. | Calgary | Alberta |
Canada | Capital District Health Auth. | Halifax | Nova Scotia |
Canada | Kingston General Hospital | Kingston | Ontario |
Canada | CHUM - Pavillon R | Montreal | Migration Data |
Canada | Royal Victoria Hospital | Montreal | Quebec |
Canada | The Bailey Clinic | Red Deer | Alberta |
Canada | LMC Thornhill/Vaughan | Thornhill | Ontario |
Canada | Mount Sinai Hospital | Toronto | Ontario |
Canada | Royal Jubilee Hospital | Victoria | British Columbia |
Canada | Health Sciences Centre Winnipeg | Winnipeg | Manitoba |
Czechia | General Univ.hosp.in Prague (VFN), Diabetes ambulance | Praha 2 | |
Czechia | Diabetology and Internal Practice Dr. Vladimir Lelek | Slany | |
Czechia | Masaryk Hospital, Internal Department | Usti nad Labem | |
Denmark | Aalborg Sygehus Syd | Aalborg | |
Denmark | Aarhus Universitets Hospital | Aarhus C | |
Denmark | Steno Diabetes Center Copenhagen | Gentofte | |
Denmark | Nordsjællands Hospital - Hillerød | Hillerød | |
Denmark | Køge Sygehus | Køge | |
Finland | IteLasaretti | Kuopio | |
Finland | Terveystalo Oulu, Diapolis | Oulu | |
Finland | TYKS | Turku | |
France | HOP Côte de Nacre | Caen | |
France | HOP Saint-Louis | La Rochelle Cedex 1 | |
France | HOP de Narbonne, diabéto endo, Narbonne | Narbonne | |
France | HOP Robert Debré | Reims | |
France | HOP de Brabois | Vandoeuvre-lès-Nancy | |
France | HOP les Portes du Sud, Diabéto, Vénissieux | Vénissieux | |
Germany | Studienzentrum Aschaffenburg | Aschaffenburg | |
Germany | Gemeinschaftspraxis, Asslar | Asslar | |
Germany | ikfe - Institut für klinische Forschung und Entwicklung Berlin GmbH | Berlin | |
Germany | InnoDiab Forschung GmbH | Essen | |
Germany | Praxis Dr. Kosch, Pirna | Pirna | |
Germany | Allgemeinmedizinische und Diabetologische Schwerpunktpraxis | Rehlingen-Siersburg | |
Germany | Praxis Dr. Hirschhäuser | Saarbrücken | |
Germany | Praxis Dr. Segner, St. Ingbert | Saint Ingbert/Oberwürzbach | |
Germany | Ambulanzzentrum Schweinfurt | Schweinfurt | |
Netherlands | Noordwest Ziekenhuisgroep | Alkmaar | |
Netherlands | Academisch Medisch Centrum (AMC) | Amsterdam | |
Netherlands | Rijnstate Hospital | Arnhem | |
Netherlands | Martini Ziekenhuis | Groningen | |
Netherlands | Bethesda Ziekenhuis Hoogeveen | Hoogeveen | |
Netherlands | Sint Franciscus Gasthuis | Rotterdam | |
Netherlands | Albert Schweitzer Ziekenhuis, Zwijndrecht | Zwijndrecht | |
Norway | Helse Møre og Romsdal HF, Ålesund sjukehus | Ålesund | |
Norway | Sykehuset Innlandet HF, Avd. Hamar | Hamar | |
Norway | Akershus Universitetssykehus HF | Lørenskog | |
Norway | Oslo Universitetssykehus HF, Aker Sykehus | Oslo | |
Poland | Med Univ Bialystok Clin Dep Endocrinol, Diabetol & Int Dis | Bialystok | |
Poland | NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny | Bialystok | |
Poland | Dobry Lekarz,Spec.Med.Clinics,Private Prac,Krakow | Krakow | |
Poland | NZOZ Specialized Ambulance "MEDICA" | Lublin | |
Poland | Marcinkowski Poznan Univ of Med Sci, Clin Dept Diab, Poznan | Poznan | |
Poland | NZOZ Centrum Medyczne AESKULAP,Private Prac, Radom | Radom | |
Poland | Centrum Medyczne Medyk | Rzeszow | |
Poland | NBR Polska | Warsaw | |
Spain | C.A.P. Sardenya | Barcelona | |
Spain | Hospital Vall d'Hebron | Barcelona | |
Spain | Hospital de la Inmaculada Concepción | Granada | |
Spain | Hospital Virgen de la Victoria | Malaga | |
Spain | Hospital General de Segovia | Segovia | |
Spain | Hospital Nuestra Señora de Valme | Sevilla | |
Spain | Hospital Virgen Macarena | Sevilla | |
Sweden | Ladulaas Kliniska Studier | Borås | |
Sweden | Centralsjukhuset, Karlstad | Karlstad | |
Sweden | Läkarhuset, Vällingby | Vällingby | |
Taiwan | China Medical University Hospital | Taichung | |
Taiwan | Chung Shan Medical University Hospital | Taichung | |
Taiwan | Chi Mei Medical Center | Tainan | |
Taiwan | National Taiwan University Hospital | Taipei | |
Taiwan | Tri-Service General Hospital | Taipei | |
United Kingdom | Milton Keynes Hospital | Buckinghamshire | |
United Kingdom | Addenbrooke's Hospital | Cambridge | |
United Kingdom | Wellcome Trust Clinical Research Facility | Edinburgh | |
United Kingdom | Leicester General Hospital | Leicester | |
United Kingdom | Royal London Hospital | London | |
United Kingdom | Queen's Medical Centre | Nottingham | |
United Kingdom | George Eliot Hospital | Nuneaton | |
United Kingdom | East Surrey Hospital | Surrey | |
United Kingdom | Queen Elizabeth II Hospital | Welwyn Garden City | |
United States | Albany Medical Center / Albany Medical College | Albany | New York |
United States | Northwest Endo Diabetes Research, LLC | Arlington Heights | Illinois |
United States | The Carl and Edyth Lindner Center for Research & Education at The Christ Hospital | Cincinnati | Ohio |
United States | Midwest Endocrinology | Crystal Lake | Illinois |
United States | North Texas Endocrine Center | Dallas | Texas |
United States | Creekside Endocrine Associates, PC | Denver | Colorado |
United States | AMCR Institute, Inc. | Escondido | California |
United States | Larry D Stonesifer, MD Inc., PS | Federal Way | Washington |
United States | The Center for Diabetes and Endocrine Care | Fort Lauderdale | Florida |
United States | Desert Endocrinology Clinical Research Center | Henderson | Nevada |
United States | Office of Dr. Michelle Zaniewski-Singh | Houston | Texas |
United States | Diabetes/Lipid Management and Research Center | Huntington Beach | California |
United States | Rocky Mountain Diabetes and Osteoporosis Center | Idaho Falls | Idaho |
United States | East Coast Institute for Research, LLC | Jacksonville | Florida |
United States | Palm Research Center | Las Vegas | Nevada |
United States | Physicians Research Associates, LLC | Lawrenceville | Georgia |
United States | National Research Institute | Los Angeles | California |
United States | Baptist Diabetes Associates, PA | Miami | Florida |
United States | Diabetes and Endocrinology Consultants, PC | Morehead City | North Carolina |
United States | Southern New Hampshire Diabetes and Endocrinology | Nashua | New Hampshire |
United States | Diabetes and Obesity Clinical Trials Center | Nashville | Tennessee |
United States | Diabetes anddocrine Associates, PC | Omaha | Nebraska |
United States | Rainier Clinical Research Center, Inc | Renton | Washington |
United States | Endocrine Research Solutions, Inc. | Roswell | Georgia |
United States | Texas Diabetes and Endocrinology | Round Rock | Texas |
United States | Bateman Horne Center | Salt Lake City | Utah |
United States | Mills-Peninsula Health Services | San Mateo | California |
United States | The Polyclinic | Seattle | Washington |
United States | Advanced Research Institute | South Ogden | Utah |
United States | University Physicians Group Research Division | Staten Island | New York |
United States | MultiCare Institute for Research and Innovation | Tacoma | Washington |
United States | Metabolic Institute of America | Tarzana | California |
United States | University Clinical Investigators, Inc. | Tustin | California |
United States | Iowa Diabetes and Endocrinology Research Center | West Des Moines | Iowa |
Lead Sponsor | Collaborator |
---|---|
Boehringer Ingelheim | Eli Lilly and Company |
United States, Australia, Austria, Belgium, Canada, Czechia, Denmark, Finland, France, Germany, Netherlands, Norway, Poland, Spain, Sweden, Taiwan, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | 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. | Week 5 to Week 26, Week 1 to Week 26 | |
Secondary | 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. | Baseline to week 26 | |
Secondary | 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. | Week 23 to 26 | |
Secondary | 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. | Week 23 to 26 | |
Secondary | 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. | Baseline to week 26 | |
Secondary | 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. | Baseline to week 26 |
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