Empagliflozin as adjunctive to insulin therapy over 26 weeks in patients with T1DM (EASE-3)

• Register: EUCTR
• Last refreshed on: 12 March 2018
• Main ID: EUCTR2014-005256-26-LV
• Date of registration: 21/09/2015
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim RCV GmbH & Co KG
• 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) - EASE-3
• Date of first enrolment: 17/11/2015
• Target sample size: 1920
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005256-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russian Federation, South Africa, Spain, Sweden, United Kingdom, United States

Contacts

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co KG

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim Pharma GmbH & Co KG

Key inclusion & exclusion 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
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 860
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

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
- Occurence of diabetic ketoacidosis within 3 months prior to Visit 1 and until Visit 6
- Irregular sleep/wake cycle
- Acute coronary syndrome, stroke or 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
- 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Patients with confirmed, insulin-dependent type 1 diabetes mellitus for at least a year
MedDRA version: 18.0 Level: LLT Classification code 10012608 Term: Diabetes mellitus insulin-dependent System Organ Class: 100000004861

Intervention(s)

Product Name: Empagliflozin
Product Code: BI 10773
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Empagliflozin
CAS Number: 864070-44-0
Current Sponsor code: BI 10773
Other descriptive name: EMPAGLIFLOZIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Jardiance
Product Name: Empagliflozin
Product Code: BI 10773
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Empagliflozin
CAS Number: 864070-44-0
Current Sponsor code: BI 10773
Other descriptive name: EMPAGLIFLOZIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Jardiance
Product Name: Empagliflozin
Product Code: BI 10773
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Empagliflozin
CAS Number: 864070-44-0
Current Sponsor code: BI 10773
Other descriptive name: EMPAGLIFLOZIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Efficacy of once daily oral doses of empagliflozin in patients with T1DM as adjunctive therapy to insulin

Secondary Objective: Safety, tolerability and PK of empagliflozin in patients with T1DM as adjunctive therapy to insulin

Timepoint(s) of evaluation of this end point: 1: 26 weeks

Primary end point(s): 1: Change from baseline in HbA1c

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1: 26 weeks

2: 26 weeks

3: Week 5 to Week 26

4: Week 1 to Week 26

5: 26 weeks

6: 26 weeks

7: Week 25 to 26

8: Week 25 to 26

9: Week 25 to 26

Secondary end point(s): 1: Change from baseline in body weight

2: Change from baseline in total daily insulin dose

3: Incidence rate of symptomatic hypoglycaemic AEs with confirmed plasma glucose < 54 mg/dL (< 3.0 mmol/L) and/or severe hypoglycaemic AEs per patient-year

4: Incidence rate of symptomatic hypoglycaemic AEs with confirmed plasma glucose < 54 mg/dL (< 3.0 mmol/L) and/or severe hypoglycaemic AEs per patient-year

5: Change from baseline in systolic blood pressure (SBP)

6: Change from baseline in diastolic blood pressure (SBP)

7: Change from baseline in the percentage of time spent in target glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) as determined by CGM

8: Change from baseline in interstitial glucose variability (inter quartile range, IQR) as determined by CGM

9: Change from baseline in AUC for interstitial glucose (mmol/24 hour) as determined by CGM

Secondary ID(s)

1245.72

2014-005256-26-DE

Source(s) of Monetary Support

Boehringer Ingelheim RCV GmbH & Co KG