Efficacy and Safety Study With Empagliflozin (BI 10773) vs. Placebo as add-on to Metformin or Metformin Plus Sulfonylurea Over 24 Weeks in Patients With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Placebo identical to BI 10773 high dose; Placebo identical to BI 10773 low dose; BI 10773; BI 10773; Placebo identical to BI 10773 low dose; BI 10773; Placebo identical to BI 10773 high dose
Intervention description: Placebo tablets matching BI 10773 high dose; Placebo tablets matching BI 10773 low dose; BI 10773 tablets once daily high dose open label; BI 10773 tablets once daily high dose; Placebo tablets matching BI 10773 low dose; BI 10773 tablets once daily low dose; Placebo tablets matching BI 10773 high dose
Intervention MeSH terms: Empagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 1504.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The objective of the current study is to investigate the efficacy, safety and tolerability of
      two doses of BI 10773 compared to placebo given for 24 weeks as add-on therapy to metformin
      or metformin plus sulfonylurea in patients with Typ 2 Diabetes Mellitus with insufficient
      glycaemic control.
    

Eligibility criteria:

        Inclusion criteria:

          1. Diagnosis of type 2 diabetes mellitus prior to informed consent

          2. Male and female patients on a diet and exercise regimen who are pre-treated with
             immediate release metformin or immediate release metformin plus sulfonylurea (see
             below for minimum doses). The treatment regimen has to be unchanged for 12 weeks prior
             to randomisation.

             Minimum dose for metformin: > or = 1500 mg/day or maximum tolerated dose or maximum
             dose according to local label Minimum dose for sulfonylurea: > or = half of the
             maximal recommended dose or maximum tolerated dose or maximum dose according to local
             label

          3. HbA1c of > or = 7.0% and < or = 11% at Visit 1 (screening) in order to be eligible for
             randomised treatment HbA1c of > 11% at Visit 1 (screening) in order to be eligible for
             the open-label treatment arm (25 mg BI 10773)

          4. Age> or = 18

          5. Body Mass Index (BM)I < or = 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 drug within 12 weeks prior to randomisation except those
             mentioned in inclusion criterion 2

          3. Myocardial infarction, stroke or transient ischemic attack (TIA) within 3 months prior
             to informed consent

          4. Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT),
             or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined during
             screening and/or run-in phase

          5. Impaired renal function, defined as eGFR<30 ml/min (severe renal impairment) as
             determined during screening and/or run-in phase

          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. Contraindications to metformin and/or sulfonylurea according to the local label for
             those patients that enter the study with the respective background therapy

          9. Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g.
             malaria, babesiosis, haemolytic anaemia)

         10. 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

         11. 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 Typ 2 Diabetes

         12. 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 study
                  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 by local
                  authorities), double barrier method and vasectomised partner

         13. 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

         14. Participation in another trial with an investigational drug within 30 days prior to
             informed consent

         15. Any other clinical condition that would jeopardize patients safety while participating
             in this clinical trial