Empagliflozin add-on to Insulin in Type 1 Diabetes Mellitus Over 28 Days
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
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
Intervention description: 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
Intervention MeSH terms: Empagliflozin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

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