Efficacy vs Placebo as Initial Combination Therapy With Pioglitazone
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: placebo + pioglitazone (30 mg); Linagliptin + pioglitazone (30 mg)
Intervention description: placebo + overcapsulated 30 mg tablet, once daily; 5 mg tablet + overcapsulated 30 mg tablet, once daily
Intervention MeSH terms: Pioglitazone; Linagliptin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 389.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The objective of the current study is to investigate the efficacy, safety and tolerability of
      BI 1356 (Linagliptin) (5 mg / once daily) compared to placebo given for 24 weeks as initial
      combination therapy with pioglitazone 30 mg in patients with type 2 diabetes mellitus with
      insufficient glycaemic control.
    

Eligibility criteria:

        Inclusion criteria:

          1. Signed and dated written Informed Consent (IC) by date of Visit 1a in accordance with
             Good Clinical Practice (GCP) and local legislation

          2. Patients with a diagnosis of type 2 diabetes mellitus and treatment naive or
             previously treated with any oral hypoglycaemic agent; antidiabetic therapy has to be
             unchanged for ten weeks prior to informed consent.

          3. Glycosylated haemoglobin A1 (HbA1c) 7.5-11% at Visit 2 (Start of Run-in).

          4. Male and female patients aged > or = 18 and < or = to 80 years at Visit 1a
             (Screening).

          5. Body Mass Index (BMI) < or = 40 kg/m2 at Visit 1a (Screening)

          6. Signed and dated written informed consent prior to admission to the study in
             accordance with GCP and local legislation.

        Exclusion criteria:

          1. Myocardial infarction, stroke or Transient Isquemic Atack (TIA) within 6 months prior
             to Inform Consent (IC)

          2. Impaired hepatic function, defined by serum levels of either Alanine Aminotransferase
             (ALT), Aspartate Aminotransferase (AST), or alkaline phosphatase above 3 x upper limit
             of normal (ULN) determined at Visit 1a.

          3. Known hypersensitivity or allergy to the investigational product or its excipients
             and/or to hydrochloride of pioglitazone or its excipients

          4. Treatment with Glucagon-like peptide-1 (GLP-1) analogue / agonist within 3 months
             prior to IC.

          5. Treatment with insulin within 3 months prior to IC

          6. Treatment with anti-obesity drugs 3 months prior to IC.

          7. Alcohol abuse within the 3 months prior to IC that would interfere with trial
             participation or drug abuse.

          8. Participation in another trial with an investigational drug within 2 months prior to
             IC.

          9. Fasting blood glucose > 240 mg/dl (=13.3 mmol/L) at screening (Visit 1).

         10. Pre-menopausal women (last menstruation < or =1 year prior to signing IC) 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 transdermal patch, intra
                  uterine devices/systems (IUDs/IUSs), oral, implantable or injectable
                  contraceptives, sexual abstinence and vasectomised partner. No exception will be
                  made.

         11. Treatment with systemic steroids or change in the dosage of thyroid hormone within six
             weeks prior to IC

         12. Heart failure New York Heart Asociation (NYHA) class I-IV, or history of heart
             failure.

         13. Diabetic ketoacidosis within 6 months prior to IC.

         14. Hemodialyzed patients due to limited experience with Thiazolidinediones (TZDs)

         15. Any other clinical condition wich, in the opinion of the investigator, would not alow
             safe completion of the protocol and safe administration of BI1356 and pioglitazone.