Empa Add on to Insulin in Japanese Patient With Type 1 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: empagliflozin medium dose; empagliflozin low dose; empagliflozin high dose; placebo
Intervention MeSH terms: Empagliflozin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 48.0
Sex: All
Minimum age: 20 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of once daily oral
      doses of empagliflozin in Japanese patients with type 1 diabetes mellitus as adjunctive
      therapy to insulin.
    

Eligibility criteria:

        Inclusion criteria:

          -  Signed and dated written informed consent by the date of Visit 1 (screening) in
             accordance with Good Clinical Practice (GCP) and local legislation

          -  Japanese male or female patient receiving insulin for treatment of documented
             diagnosis of type 1 diabetes mellitus (T1DM) for at least 1 year at the time of Visit
             1 (screening).

          -  Fasting C-peptide value of < 0.6 ng/mL at Visit 2 (placebo run-in) measured by the
             central laboratory

          -  Use of, and be willing, based on the investigator's judgment, to continue throughout
             the duration of the trial Multiple daily injection(MDI) of insulin consisting of at
             least 1 basal insulin injection and at least 3 daily bolus injections The total daily
             insulin dose must be>=0.3 U/kg and <=1.5 U/kg at Visit 1 (screening)

          -  HbA1c of 7.5% to 10.0% at Visit 1 (screening) measured by the central laboratory and
             provided that the patients HbA1c does not increase by > 0.5% within 3 months before
             Visit 1 (screening)

          -  Based on the investigator's judgment, patient must have a good understanding of
             his/her disease and how to manage it, and be willing and capable of performing the
             following study assessments (assessed at Visits 1 to 3 and just before randomization)

          -  patient-led management and adjustment of insulin therapy

          -  reliable approach to insulin dose adjustment for meals, such as carbohydrate counting

          -  reliable and regular home-based blood glucose monitoring

          -  recognize the symptoms of DKA (Diabetic Ketoacidosis), and reliably monitor for
             ketones

          -  implementation of an established "sick day" management regimen

          -  Age >=20 years and <=65 years at Visit 1 (screening)

          -  Body mass index (BMI) >=18.5 kg/m2 and<=35.0 kg/m2 at Visit 1 (screening)

          -  Estimated glomerular filtration rate (eGFR) >=60 mL/min/1.73m² and <=150 mL/min/1.73m²
             as calculated by Japanese equation based on creatinine measured by the central
             laboratory at Visit 1 (screening)

          -  Compliance with trial drug administration must be between 80% and 120% during the
             placebo run-in period, to be judged at Visit 4 and before randomization

        Exclusion criteria:

          -  History of T2DM (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 anti-hyperglycaemic drug (e.g., metformin,
             alpha-glycosidase inhibitors, glucagon-like-peptide 1 (GLP-1) receptor agonists,
             SGLT-2 (Sodium-Glucose co-transporter-2) inhibitors, pramlintide, inhaled insulin,
             pre-mixed insulins, etc.) within 3 months except subcutaneous basal and bolus insulin
             before Visit 1 (screening) or any history of clinically relevant hypersensitivity
             according to the investigator's judgment

          -  Occurrence of severe hypoglycemia involving coma and/or seizure that required
             hospitalization or hypoglycemia-related treatment by an emergency physician or
             paramedic within 3 months before Visit 1 (screening)

          -  Occurrence of DKA within 3 months before Visit 1 (screening) and until randomization
             at Visit 4 (Day 1)

          -  Irregular sleep/wake cycle (e.g., patients who habitually sleep during the day and
             work during the night) based on the investigator's judgment

          -  Acute coronary syndrome (non-STEMI, STEMI, and unstable angina pectoris), stroke or
             transient ischemic attack within 3 months before Visit 1 (screening)

          -  Diagnosis of severe gastro paresis based on investigator's judgment

          -  Diagnosis of brittle diabetes based on the investigator's judgment

          -  Indication of liver impairment, defined by serum levels of either alanine transaminase
             (ALT), aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of
             normal (ULN) at Visit 1 (screening) as measured by the central laboratory

          -  Eating disorders such as bulimia or anorexia nervosa

          -  Treatment with anti-obesity drugs (e.g., Mazindol), surgery or aggressive diet regimen
             leading to unstable body weight (based on the investigator's judgment) 3 months before
             Visit 1 (screening) and until randomization

          -  Treatment with systemic corticosteroids or planned initiation of such therapy at Visit
             1 (screening). Inhaled use of corticosteroids (e.g., for asthma/chronic obstructive
             pulmonary disease) is acceptable

          -  Change in dose of thyroid hormones within 6 weeks before Visit 1 (screening) or
             planned change or initiation of such a therapy at Visit 1 (screening)

          -  Medical history of cancer or treatment for cancer in the last 5 years before Visit 1
             (screening). Resected basal cell carcinoma considered cured is exempted

          -  Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells (e.g.,
             malaria, babesiosis, hemolytic anemia) at Visit 1 (screening)

          -  Pre-menopausal women (last menstruation <=1 year before informed consent) who:

          -  are nursing or pregnant or

          -  are of child-bearing potential and are not practicing an acceptable method of birth
             control, or do not plan to continue using this method throughout the study and do not
             agree to submit to periodic pregnancy testing during participation in the trial.
             Acceptable methods of birth control include tubal ligation, intra uterine
             devices/systems, oral contraceptives, complete sexual abstinence, double barrier
             method and vasectomized partner

          -  Alcohol or drug abuse within 3 months before Visit 1 (screening) that would interfere
             with trial participation based on the investigator's judgment

          -  Intake of an investigational drug in another trial within 30 days before Visit 1
             (screening)

          -  Patient not able to understand and comply with study requirements based on the
             investigator's judgment

          -  Any other clinical condition that, based on investigator's judgment, would jeopardise
             patient safety or would affect the study outcome (e.g. immunocompromised patients who
             might be at higher risk of developing genital or mycotic infections, patients with
             chronic viral infections, etc.) during trial participation