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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02580591




Registration number
NCT02580591
Ethics application status
Date submitted
19/10/2015
Date registered
20/10/2015
Date last updated
2/11/2018

Titles & IDs
Public title
Empagliflozin as Adjunctive to Insulin Therapy Over 26 Weeks in Patients With T1DM (EASE-3)
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 26 Weeks in Patients With Type 1 Diabetes Mellitus (EASE-3)
Secondary ID [1] 0 0
2014-005256-26
Secondary ID [2] 0 0
1245.72
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 - Placebo

Experimental: Empagliflozin low dose -

Experimental: Empagliflozin high dose -

Experimental: Empagliflozin medium dose -

Placebo Comparator: Placebo -


Treatment: Drugs: Empagliflozin


Treatment: Drugs: Placebo
For blinding purposes

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

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 for Full Analysis Set (FAS) (Observed Cases [OC]) - Change from baseline in Glycated hemoglobin (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 randomized trial medication. Least squares mean is adjusted mean change from baseline.
Timepoint [1] 0 0
Baseline to week 26
Primary outcome [2] 0 0
Change From Baseline in Glycated Hemoglobin (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 hemoglobin (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 randomized trial medication. Least squares mean is adjusted mean change from baseline.
Timepoint [2] 0 0
Baseline to week 26
Secondary outcome [1] 0 0
Rate Per Patient-year of Investigator-reported Symptomatic Hypoglycemic Adverse Events (AEs) With Confirmed Plasma Glucose (PG) - Rate per patient-year of investigator-reported symptomatic hypoglycemic adverse events (AEs) with confirmed plasma glucose (PG) <54 milligram per deciliter (mg/dL) (<3.0 millimoles per litre (mmol/L)) and/or severe hypoglycemic AEs (i.e. all investigator-reported AEs that had confirmed PG <54 mg/dL [<3.0 mmol/L] with symptoms reported and all severe hypoglycemic 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. This is key secondary endpoints.
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 randomized 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 Total Daily Insulin Dose (TDID) at Week 26 - Change from baseline in Total daily insulin dose (TDID) is presented. With regards to efficacy and safety endpoints, the term 'baseline' referred to the last observed measurement prior to administration of any randomized trial medication. Least squares mean is adjusted mean change from baseline.
Timepoint [3] 0 0
Baseline to week 26
Secondary outcome [4] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 26 - Change from baseline in Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) is presented. With regards to efficacy and safety endpoints, the term 'baseline' referred to the last observed measurement prior to administration of any randomized trial medication. Least squares mean is adjusted mean change from baseline.
Timepoint [4] 0 0
Baseline to week 26

Eligibility
Key inclusion criteria
Inclusion criteria:

- Signed and dated written informed consent

- Male or female patient receiving insulin for the treatment of documented diagnosis of
type 1 diabetes mellitus (T1DM) > 1 year

- C-peptide value of < 0.7 ng/mL

- Use of Multiple Daily Injections (MDI) of insulin or insulin pump user with total
daily insulin >= 0.3 and <= 1.5 U/kg

- Glycated haemoglobin (HbA1c) >= 7.5% and <= 10.0%

- Good understanding of T1DM

- Age >= 18 years

- Body Mass Index (BMI) >= 18.5 kg/m2

- Estimated glomerular filtration rate >= 30 mL/min/1.73 m2

- Women of child-bearing potential must use highly effective methods of birth control

- Compliance with trial medication administration between 80% and 120% during placebo
run-in period Further inclusion criteria 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, 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 except subcutaneous basal and
bolus insulin within last 3 months

- Occurrence of severe hypoglycaemia within last 3 months and until randomisation

- Occurence of diabetic ketoacidosis within 3 months prior to Visit 1 and until Visit 6

- Irregular sleep/wake cycle

- Acute coronary syndrome, stroke or Transient Ischaemic Attack (TIA) within last 3
months

- Severe gastroparesis

- Brittle diabetes

- Liver disease

- Eating disorders

- Treatment with anti-obesity drugs, weight-loss surgery or aggressive diet regimen

- Treatment with systemic corticosteroids

- Change in dose of thyroid hormones within last 6 weeks and until randomisation

- Cancer or treatment for cancer in the last five years

- Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells

- Women who are pregnant, nursing, or who plan to become pregnant whilst in the trial

- Alcohol or drug abuse

- Intake of an investigational drug in another trial within last 30 days Further
exclusion criteria 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,SA,VIC
Recruitment hospital [1] 0 0
Coffs Endocrine & Diabetes Services - Coffs Harbour
Recruitment hospital [2] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [3] 0 0
SA Endocrine Research P/L - Keswick
Recruitment hospital [4] 0 0
Eastern Clinical Research Unit - East Ringwood
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
5035 - Keswick
Recruitment postcode(s) [4] 0 0
3135 - East Ringwood
Recruitment outside Australia
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Nottingham
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Nuneaton

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
The study will investigate the efficacy, safety, tolerability and Pharmacokinetic(PK) of 3
doses of empagliflozin compared with placebo over 26 weeks in 960 patients with type 1
diabetes mellitus as adjunctive therapy to insulin
Trial website
https://clinicaltrials.gov/show/NCT02580591
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
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications