Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses of BI 10773 Tablets
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: BI 10773 Placebo; BI 10773; BI 10773 Placebo; BI 10773; BI 10773 Placebo; BI 10773 Placebo; BI 10773; BI 10773
Intervention description: po taken fasting with 240 mL water; po taken fasting with 240 mL water; po taken fasting with 240 mL water; po taken fasting with 240 mL water; po taken fasting with 240 mL water; po taken fasting with 240 mL water; po taken fasting with 240 mL water; po taken fasting with 240 mL water
Intervention MeSH terms: Empagliflozin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      To investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BI 10773 with
      repeat dosing for eight days and the exploration of the pharmacokinetics and pharmacodynamics
      of BI 10773 after multiple dosing, including dose proportionality and assessment of steady
      state.
    

Eligibility criteria:

        Inclusion criteria:

          1. Male and postmenopausal or hysterectomised female patients with proven diagnosis of
             type 2 diabetes mellitus treated with diet and exercise only or on a maximum of two
             oral antidiabetic agents except thiazolidindiones with at least one agent taken at 50%
             of its maximum dose or less.

          2. Glycosylated haemoglobin A1 (HbA1c) £ 8.5 % at screening.

          3. Age >21 and Age <70 years (male and hysterectomised female patients) Age >60 and Age
             <70 years (postmenopausal female patients)

          4. Body Mass Index (BMI) >18.5 and <40 kg/m2

          5. Signed and dated written informed consent prior to admission to the study in
             accordance with GCP and the local legislation

        Exclusion criteria:

          1. Antidiabetic treatment with insulin or glitazones or with more than one oral
             hypoglycaemic agent (except if 2 agents and at least one of them not taken at more
             than 50% of its maximum dose)

          2. Fasted blood glucose > 240 mg/dl (>13.3 mmol/L) on two consecutive days during
             washout.

          3. Glycosylated haemoglobin A1 (HbA1c) >8.5% at screening

          4. Clinically relevant concomitant diseases other than type 2 diabetes, hyperlipidaemia
             and medically treated hypertension, such as:

               -  Any late stage complication of diabetes (e.g. retinopathy, polyneuropathy,
                  vegetative disorders, diabetic foot)

               -  Renal insufficiency (calculated creatinine clearance < 80 ml/min/1.73m²)

               -  Cardiac insufficiency NYHA II-IV, myocardial infarction, other known
                  cardiovascular diseases including hypertension > 160/95mmHg (measured at training
                  visit and each of the timepoints of Day -1), stroke and TIA (Transistoric
                  ischaemic attack)

               -  Neurological disorders (such as epilepsy) or psychiatric disorders

               -  Acute or relevant chronic infections (e.g. HIV, repeated urogenital infections)

               -  Any gastrointestinal, hepatic, respiratory, endocrine or immunological disorder

          5. History of relevant allergy/hypersensitivity (including allergy to drug or its
             excipients)

          6. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a
             QTc interval >450 ms)

          7. A history of additional risk factors for TdP (torsade des pointes) (e.g., heart
             failure, hypokalemia, family history of sudden death before the age of 50)