Efficacy and Safety of 3 Doses of BI1356 (Linagliptin) in Type 2 Diabetes Patients
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Placebo; BI 1356 dose 3 once daily; BI 1356 dose 2 once daily; BI 1356 dose 1 once daily; Metformin
Intervention description: Placebo matching BI 1356; BI 1356 dose 3 once daily; BI 1356 dose 2 once daily; BI 1356 dose 1 once daily; Metformin
Intervention MeSH terms: Metformin; Linagliptin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 302.0
Sex: All
Minimum age: 21 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The objective of the current study is to investigate the efficacy, safety and tolerability of
      several doses of BI 1356 BS (0.5, 2.5 and 5 mg daily) compared to placebo over 12 weeks of
      treatment in patients with Type 2 diabetes and insufficient glycemic control. In addition,
      there will be an open-label treatment arm with metformin for sensitivity measurement with
      this patient population. Population pharmacokinetics of BI 1356 BS will also be assessed in
      this study.
    

Eligibility criteria:

        Inclusion criteria:

          1. Male and female patients with a diagnosis of Type 2 diabetes treated only with diet
             and exercise (drug naïve) or with one or two oral hypoglycemic agents (as single
             treatment or in combination) other than rosiglitazone or pioglitazone -treatment.
             Antidiabetic therapy has to be stable for at least 10 weeks prior to screening.

          2. Diagnosis of Type 2 diabetes with duration of at least 3 months

          3. Glycosylated haemoglobin A1 (HbA1c) of:

             7.5-10.0% at screening for drug naïve patients (no wash-out needed) 7.0-9.0% at
             screening for patients treated with only one oral antidiabetic agent (wash-out
             required) 6.5-8.0% at screening for patients treated with two oral antidiabetic agents
             (wash-out required)

          4. HbA1c of 7.5%-10.0% at Visit 3 (beginning of the 2-week placebo run-in period).

          5. Age >=21 and <=75 years.

          6. BMI (Body Mass Index) >=25.0 and <=40 kg/m2.

          7. Signed and dated written informed consent prior to admission to the study in
             accordance with Good Clinical Practice (GCP) and local legislation

        Exclusion criteria:

          1. Clinically relevant cardiovascular disease (e.g., myocardial infarction, stroke or
             transient ischemic attack within six months before enrollment)

          2. Impaired hepatic function defined by serum levels of either alanine aminotransferase,
             aspartate aminotransferase or alkaline phosphatase above 3-fold upper limit of normal

          3. Renal insufficiency or impaired renal function defined by serum creatinine above upper
             limit of normal at screening

          4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or
             clinically relevant neurologic disorders (including cerebrovascular but with the
             exception of polyneuropathy) that would interfere with participation in the trial

          5. Chronic or clinically relevant acute infections (e.g., Human immunodeficiency virus,
             Hepatitis)

          6. History of relevant allergy/hypersensitivity that would interfere with trial
             participation (including allergy to investigational product or its excipients)

          7. Treatment with rosiglitazone or pioglitazone within 6 months prior to screening

          8. Treatment with insulin within 3 months prior to screening

          9. Alcohol or drug abuse within the last 3 months that would interfere with trial
             participation)

         10. Participation in another trial with an investigational drug within two months prior to
             administration or during the trial

         11. Fasting plasma glucose >240 mg/dl (= 13.3 mmol/L) at Visit 2, 3 or 4 any visit and
             confirmed by a second measurement (not on the same day)

         12. Pre-menopausal women (last menstruation <=1 year prior to signing informed consent)
             who:

               1. are not surgically sterile,

               2. or are nursing or pregnant;

               3. 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, oral, implantable or injectable contraceptives and
                  vasectomised partner. No exception will be made.

         13. Intolerance of metformin