Empagliflozin add-on to Insulin in Type 1 Diabetes Mellitus Over 28 Days

Diabetes Mellitus, Type 1 Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01969747
• Other study ID #: 1245.78
• Secondary ID: 2011-004354-25
• Status: Completed
• Phase: Phase 2
• First received: October 22, 2013
• Last updated: April 6, 2015
• Start date: November 2013
• Est. completion date: April 2014

Study information

• Verified date: April 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• Empagliflozin medium placebo
Empagliflozin medium placebo
• Empagliflozin low placebo
Empagliflozin low placebo
• Empagliflozin low placebo
Empagliflozin low placebo
• Empagliflozin high placebo
Empagliflozin high placebo
• Empagliflozin medium
Empagliflozin medium
• Empagliflozin medium placebo
Empagliflozin medium placebo
• Empagliflozin high placebo
Empagliflozin high placebo
• Empagliflozin high placebo
Empagliflozin high placebo
• Empagliflozin medium placebo
Empagliflozin medium placebo
• Empagliflozin low placebo
Empagliflozin low placebo
• Empagliflozin low
Empagliflozin low
• Empagliflozin high
Empagliflozin high

Locations

Country	Name	City	State
Austria	1245.78.43001 Boehringer Ingelheim Investigational Site	Graz
Germany	1245.78.49001 Boehringer Ingelheim Investigational Site	Neuss

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	baseline (Day -1) and 7 days after first drug administration (Day 7)	No

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