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

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: Empagliflozin medium; Drug: Empagliflozin low; Drug: Empagliflozin high placebo; Drug: Empagliflozin low placebo; Drug: Empagliflozin medium placebo; Drug: Empagliflozin high

Study type: Interventional

Funder types: Industry

Identifiers

NCT01969747

1245.78

2011-004354-25 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 75 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

75 participants in 4 patient groups, including a placebo group

Empagliflozin low

Experimental group

Description:

Empagliflozin low once daily

Treatment:

Drug: Empagliflozin medium placebo

Drug: Empagliflozin high placebo

Drug: Empagliflozin high placebo

Drug: Empagliflozin medium placebo

Drug: Empagliflozin medium placebo

Drug: Empagliflozin high placebo

Drug: Empagliflozin low

Empagliflozin medium

Experimental group

Description:

Empagliflozin medium once daily

Treatment:

Drug: Empagliflozin high placebo

Drug: Empagliflozin low placebo

Drug: Empagliflozin high placebo

Drug: Empagliflozin high placebo

Drug: Empagliflozin low placebo

Drug: Empagliflozin low placebo

Drug: Empagliflozin medium

Empagliflozin high

Experimental group

Description:

Empagliflozin high once daily

Treatment:

Drug: Empagliflozin medium placebo

Drug: Empagliflozin low placebo

Drug: Empagliflozin high

Drug: Empagliflozin medium placebo

Drug: Empagliflozin medium placebo

Drug: Empagliflozin low placebo

Drug: Empagliflozin low placebo

Placebo

Placebo Comparator group

Description:

Placebo once daily

Treatment:

Drug: Empagliflozin medium placebo

Drug: Empagliflozin high placebo

Drug: Empagliflozin low placebo

Drug: Empagliflozin high placebo

Drug: Empagliflozin medium placebo

Drug: Empagliflozin medium placebo

Drug: Empagliflozin high placebo

Drug: Empagliflozin low placebo

Drug: Empagliflozin low placebo