Empagliflozin add-on to Insulin in Type 1 Diabetes Mellitus Over 28 Days
Primary Purpose
Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Empagliflozin medium placebo
Empagliflozin low placebo
Empagliflozin low placebo
Empagliflozin high placebo
Empagliflozin medium
Empagliflozin medium placebo
Empagliflozin high placebo
Empagliflozin high placebo
Empagliflozin medium placebo
Empagliflozin low placebo
Empagliflozin low
Empagliflozin high
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1
Eligibility Criteria
Inclusion criteria:
- Signed and dated written informed consent
- Male or female patient receiving insulin for treatment of T1DM for at least 12 months
- C-peptide < 1.5 ng/mL
- Age 18 to 65 years
- HbA1c of 7.5% to 10.5%
- Multiple daily injections (MDI) of any type of insulin
- Willing to follow an established and individualized carbohydrate counting method and an insulin administration algorithm
- Body Mass Index of 18.5 to 35.0 kg/m2
- Estimated glomerular filtration rate 60 to 150 mL/min/1.73 m²
- Able and willing to perform study assessments according to investigator's judgement
- Compliance with trial drug administration 80% to 120% during run-in period
- Willing not to take any paracetamol containing drugs during the trial
Exclusion criteria:
- Acute symptomatic urinary tract infection or genital infection, chronic or recurrent cystitis
- 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
- Type 1 diabetes mellitus treatment with any other antihyperglycaemic drug except insulin within last 3 months or history of clinically relevant hypersensitivity
- Occurrence of hypoglycaemia that required hospitalization or treatment by an emergency physician or paramedic within last 3 months
- Hypoglycaemia unawareness or frequent episodes of unexplained hypoglycaemia
- Occurrence of diabetic ketoacidosis that required hospitalization or treatment by an emergency physician or paramedic within last 12 months
- History of macrovascular disease including cardiovascular, cerebrovascular and peripheral artery disease
- Autonomic neuropathy with gastroparesis
- Brittle diabetes
- Liver disease
- Treatment with anti-obesity drugs, surgery or aggressive diet regimen leading to unstable body weight
- Treatment with systemic corticosteroids
- Change in dose of thyroid hormones within last 6 weeks or planned change or initiation of such a therapy
- Medical history of cancer or treatment for cancer in the last five years
- Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells
- Alcohol or drug abuse that would interfere with trial participation or any ongoing clinical condition that would jeopardize patient's or site personnel's safety or study compliance
- Intake of an investigational drug in another trial within last 30 days
- Not able to understand and comply with study requirements
- Pre-menopausal women who are nursing or pregnant or of child-bearing potential and are not practising an acceptable method of birth control
Sites / Locations
- 1245.78.43001 Boehringer Ingelheim Investigational Site
- 1245.78.49001 Boehringer Ingelheim Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Empagliflozin low
Empagliflozin medium
Empagliflozin high
Placebo
Arm Description
Empagliflozin low once daily
Empagliflozin medium once daily
Empagliflozin high once daily
Placebo once daily
Outcomes
Primary Outcome Measures
Change From Baseline in 24 h UGE (g/24 h) After Seven Days of Treatment With Empagliflozin 2.5 mg, 10 mg, or 25 mg, or Placebo
Change of urinary glucose excretion (UGE) (g/24 h) from baseline (refers to the last measurement prior to the first intake of any randomised trial medication) after seven days of treatment with empagliflozin 2.5 mg, 10 mg, or 25 mg, or placebo.
The treatment effect was estimated on the basis of the least square mean treatment difference at Day 7 extracted from the primary analysis model.
The primary endpoint is exploratory.
Secondary Outcome Measures
Full Information
NCT ID
NCT01969747
First Posted
October 22, 2013
Last Updated
April 6, 2015
Sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT01969747
Brief Title
Empagliflozin add-on to Insulin in Type 1 Diabetes Mellitus Over 28 Days
Official Title
A 28-day Randomised, Placebo-controlled, Double-blind Parallel Group Phase IIa Trial to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Once Daily Oral Doses of 2.5 mg, 10 mg, and 25 mg Empagliflozin as Adjunctive to Insulin in Patients With Type 1 Diabetes Mellitus (EASE-2)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
November 2013 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
Collaborators
Eli Lilly and Company
4. Oversight
5. Study Description
Brief Summary
Placebo-controlled, double blind (triple-dummy technique), randomised parallel design comparison of three oral doses (2.5 mg, 10 mg, and 25 mg) of empagliflozin in patients with T1DM as adjunctive therapy to insulin over 28 days. Patients will undergo a 14-day open-label placebo run-in period before randomisation. Background insulin therapy will be kept stable during the first 7 days of the treatment period and will be freely adjusted thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Empagliflozin low
Arm Type
Experimental
Arm Description
Empagliflozin low once daily
Arm Title
Empagliflozin medium
Arm Type
Experimental
Arm Description
Empagliflozin medium once daily
Arm Title
Empagliflozin high
Arm Type
Experimental
Arm Description
Empagliflozin high once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo once daily
Intervention Type
Drug
Intervention Name(s)
Empagliflozin medium placebo
Intervention Description
Empagliflozin medium placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin low placebo
Intervention Description
Empagliflozin low placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin low placebo
Intervention Description
Empagliflozin low placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin high placebo
Intervention Description
Empagliflozin high placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin medium
Intervention Description
Empagliflozin medium
Intervention Type
Drug
Intervention Name(s)
Empagliflozin medium placebo
Intervention Description
Empagliflozin medium placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin high placebo
Intervention Description
Empagliflozin high placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin high placebo
Intervention Description
Empagliflozin high placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin medium placebo
Intervention Description
Empagliflozin medium placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin low placebo
Intervention Description
Empagliflozin low placebo
Intervention Type
Drug
Intervention Name(s)
Empagliflozin low
Intervention Description
Empagliflozin low
Intervention Type
Drug
Intervention Name(s)
Empagliflozin high
Intervention Description
Empagliflozin high
Primary Outcome Measure Information:
Title
Change From Baseline in 24 h UGE (g/24 h) After Seven Days of Treatment With Empagliflozin 2.5 mg, 10 mg, or 25 mg, or Placebo
Description
Change of urinary glucose excretion (UGE) (g/24 h) from baseline (refers to the last measurement prior to the first intake of any randomised trial medication) after seven days of treatment with empagliflozin 2.5 mg, 10 mg, or 25 mg, or placebo.
The treatment effect was estimated on the basis of the least square mean treatment difference at Day 7 extracted from the primary analysis model.
The primary endpoint is exploratory.
Time Frame
baseline (Day -1) and 7 days after first drug administration (Day 7)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Signed and dated written informed consent
Male or female patient receiving insulin for treatment of T1DM for at least 12 months
C-peptide < 1.5 ng/mL
Age 18 to 65 years
HbA1c of 7.5% to 10.5%
Multiple daily injections (MDI) of any type of insulin
Willing to follow an established and individualized carbohydrate counting method and an insulin administration algorithm
Body Mass Index of 18.5 to 35.0 kg/m2
Estimated glomerular filtration rate 60 to 150 mL/min/1.73 m²
Able and willing to perform study assessments according to investigator's judgement
Compliance with trial drug administration 80% to 120% during run-in period
Willing not to take any paracetamol containing drugs during the trial
Exclusion criteria:
Acute symptomatic urinary tract infection or genital infection, chronic or recurrent cystitis
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
Type 1 diabetes mellitus treatment with any other antihyperglycaemic drug except insulin within last 3 months or history of clinically relevant hypersensitivity
Occurrence of hypoglycaemia that required hospitalization or treatment by an emergency physician or paramedic within last 3 months
Hypoglycaemia unawareness or frequent episodes of unexplained hypoglycaemia
Occurrence of diabetic ketoacidosis that required hospitalization or treatment by an emergency physician or paramedic within last 12 months
History of macrovascular disease including cardiovascular, cerebrovascular and peripheral artery disease
Autonomic neuropathy with gastroparesis
Brittle diabetes
Liver disease
Treatment with anti-obesity drugs, surgery or aggressive diet regimen leading to unstable body weight
Treatment with systemic corticosteroids
Change in dose of thyroid hormones within last 6 weeks or planned change or initiation of such a therapy
Medical history of cancer or treatment for cancer in the last five years
Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells
Alcohol or drug abuse that would interfere with trial participation or any ongoing clinical condition that would jeopardize patient's or site personnel's safety or study compliance
Intake of an investigational drug in another trial within last 30 days
Not able to understand and comply with study requirements
Pre-menopausal women who are nursing or pregnant or of child-bearing potential and are not practising an acceptable method of birth control
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1245.78.43001 Boehringer Ingelheim Investigational Site
City
Graz
Country
Austria
Facility Name
1245.78.49001 Boehringer Ingelheim Investigational Site
City
Neuss
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
27929674
Citation
Famulla S, Pieber TR, Eilbracht J, Neubacher D, Soleymanlou N, Woerle HJ, Broedl UC, Kaspers S. Glucose Exposure and Variability with Empagliflozin as Adjunct to Insulin in Patients with Type 1 Diabetes: Continuous Glucose Monitoring Data from a 4-Week, Randomized, Placebo-Controlled Trial (EASE-1). Diabetes Technol Ther. 2017 Jan;19(1):49-60. doi: 10.1089/dia.2016.0261. Epub 2016 Dec 8.
Results Reference
derived
PubMed Identifier
24746173
Citation
Lamos EM, Younk LM, Davis SN. Empagliflozin, a sodium glucose co-transporter 2 inhibitor, in the treatment of type 1 diabetes. Expert Opin Investig Drugs. 2014 Jun;23(6):875-82. doi: 10.1517/13543784.2014.909407. Epub 2014 Apr 19.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/
Description
Related Info
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Empagliflozin add-on to Insulin in Type 1 Diabetes Mellitus Over 28 Days
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