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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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
Treatment: Drugs - Empagliflozin
Treatment: Drugs - Empagliflozin
Treatment: Drugs - Placebo

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


Treatment: Drugs: Empagliflozin


Treatment: Drugs: Empagliflozin


Treatment: Drugs: Placebo


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
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) ) - 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.
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) - 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.
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 - 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.
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 - 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.
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 - 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.
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 - 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.
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 - 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.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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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Surrey
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Welwyn Garden City

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/show/NCT02414958
Trial related presentations / publications
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
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications