Efficacy and Safety of Empagliflozin (BI 10773) in Type 2 Diabetes Patients on a Background of Pioglitazone Alone or With Metformin
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Placebo; BI 10773; Placebo; Placebo; Placebo; BI 10773
Intervention description: Placebo tablets matching BI 10773 low dose; BI 10773 tablets once daily; Placebo tablets matching BI 10773 high dose; Placebo tablets matching BI 10773 high dose; Placebo tablets matching BI 10773 high dose; BI 10773 tablets once daily
Intervention MeSH terms: Empagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 499.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will investigate the efficacy and safety of BI 10773 in type 2 diabetic patients
      in order to provide these data for approval for BI 10773 by regulatory authorities as an
      antidiabetic agent as add-on therapy to pioglitazone alone or in combination with metformin.
    

Eligibility criteria:

        Inclusion criteria:

          1. Diagnosis of type 2 diabetes mellitus prior to informed consent.

          2. Male and female patients on diet and exercise regimen who are pre-treated with
             pioglitazone alone or in combination with metformin. The treatment regimen should be
             unchanged for 12 weeks prior to randomisation.

          3. HbA1c of >/= 7.0% and </= 10.0% at Visit 1 (screening).

          4. Age >/= 18.

          5. BMI </= 45 kg/m2 (Body Mass Index) at Visit 1 (screening).

          6. Signed and dated written informed consent by date of Visit 1 in accordance with Good
             Clinical Practice (GCP) and local legislation.

        Exclusion criteria:

          1. Uncontrolled hyperglycaemia with a glucose level > 240 mg/dl (> 13.3 mmol/l) after an
             overnight fast during placebo run-in and confirmed by a second measurement (not on the
             same day).

          2. Any other antidiabetic medication within 12 weeks prior to randomisation, except those
             defined as the permitted background therapy via inclusion criteria no. 2.

          3. Myocardial infarction, stroke or transient ischaemic attack (TIA) within 3 months
             prior to informed consent.

          4. Indication of liver disease, defined by serum levels of either alanine transaminase
             (ALT/SGPT), aspartate transaminase (AST/SGOT), or alkaline phosphatase above 3 x upper
             limit of normal (ULN) as determined during screening or during the placebo run-in
             period (i.e. at a visit prior to the randomisation visit, Visit 3).

          5. Impaired renal function, defined as eGFR (estimated Glomerular Filtration Rate) < 30
             ml/min (severe renal impairment, MDRD [Modification of Diet in Renal Disease] formula)
             as determined during screening or during the placebo run-in period (i.e. at a visit
             prior to the randomisation visit, Visit 3).

          6. Bariatric surgery within the past two years and other gastrointestinal surgeries that
             induce chronic malabsorption.

          7. Medical history of cancer (except for basal cell carcinoma) and/or treatment for
             cancer within the last 5 years .

          8. Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g.
             malaria, babesiosis, haemolytic anaemia).

          9. Contraindications to pioglitazone according to the local label.

         10. Contraindication to pioglitazone and/or metformin (relevant only for those patients
             who enter the study with both these background therapies) according to the local
             labels.

         11. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to
             informed consent or any other treatment at the time of screening (i.e. surgery,
             aggressive diet regimen etc.) leading to unstable body weight.

         12. Current treatment with systemic steroids at time of informed consent or change in
             dosage of thyroid hormones within 6 weeks prior to informed consent or any other
             uncontrolled endocrine disorder except T2D.

         13. Pre-menopausal women (last menstruation </= 1 year prior to 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 trial
                  and do not agree to submit to periodic pregnancy testing during participation in
                  the trial. Acceptable methods of birth control include tubal ligation,
                  transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable
                  or injectable contraceptives, sexual abstinence (if acceptable to local
                  authorities), double barrier method and vasectomised partner.

         14. Alcohol or drug abuse within the 3 months prior to informed consent that would
             interfere with trial participation or any ongoing condition leading to a decreased
             compliance to study procedures or study drug intake.

         15. Participation in another trial with an investigational drug within 30 days prior to
             informed consent.

         16. Any other clinical condition that would jeopardise patient safety while participating
             in this clinical trial.