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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02414958




Registration number
NCT02414958
Ethics application status
Date submitted
8/04/2015
Date registered
13/04/2015
Date last updated
3/01/2019

Titles & IDs
Public title
Empagliflozin as Adjunctive to InSulin thErapy Over 52 Weeks in Patients With Type 1 Diabetes Mellitus (EASE-2)
Scientific 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)
Secondary ID [1] 0 0
2014-001922-14
Secondary ID [2] 0 0
1245.69
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 1 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Empagliflozin low dose - Empagliflozin tablets once daily

Experimental: Empagliflozin high dose - Empagliflozin tablets once daily

Placebo comparator: Placebo - Placebo tablets matching empagliflozin once daily
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 26
Timepoint [1] 0 0
Baseline to week 26
Primary outcome [2] 0 0
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) )
Timepoint [2] 0 0
Baseline to week 26
Secondary outcome [1] 0 0
Rate Per Patient-year of Investigator-reported Symptomatic Hypoglycaemia Adverse Events (AEs) With Confirmed Plasma Glucose (PG)
Timepoint [1] 0 0
Week 5 to Week 26, Week 1 to Week 26
Secondary outcome [2] 0 0
Change From Baseline in Body Weight at Week 26
Timepoint [2] 0 0
Baseline to week 26
Secondary outcome [3] 0 0
Change From Baseline in Percentage of Time Spent in Target Glucose Range From Weeks 23 to 26
Timepoint [3] 0 0
Week 23 to 26
Secondary outcome [4] 0 0
Change From Baseline in Interstitial Glucose Variability Based on the Interquartile Range (IQR) as Determined by CGM in Weeks 23 to 26
Timepoint [4] 0 0
Week 23 to 26
Secondary outcome [5] 0 0
Change From Baseline in Total Daily Insulin Dose (TDID) at Week 26
Timepoint [5] 0 0
Baseline to week 26
Secondary outcome [6] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 26
Timepoint [6] 0 0
Baseline to week 26

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/10/2017
Sample size
Target
Accrual to date
Final
730
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Coffs Endocrine & Diabetes Services - Coffs Harbour
Recruitment hospital [2] 0 0
AIM Centre - Merewether
Recruitment hospital [3] 0 0
Royal Brisbane & Women's Hospital-Endocrinology - Herston
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
2291 - Merewether
Recruitment postcode(s) [3] 0 0
4006 - Herston
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02414958
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02414958