Efficacy and Safety Study of Linagliptin (5 mg Administered Orally Once Daily) Over 24 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Linagliptin; placebo
Intervention description: once a day; once a day
Intervention MeSH terms: Linagliptin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 306.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      In this randomised, double-blind, parallel group trial, the safety and efficacy of 5 mg of
      Linagliptin administered orally once daily will be compared with a placebo after 24 weeks of
      treatment as add-on therapy to metformin in patients with type 2 diabetes and insufficient
      glycaemic control.
    

Eligibility criteria:

        Inclusion criteria:

          1. Male and female patients with a diagnosis of type 2 diabetes mellitus and previously
             treated with metformin alone, or with metformin and not more than one other oral
             antidiabetic drug (antidiabetic therapy has to be unchanged for 6 weeks prior to
             informed consent and patients should receive standard diet and exercise counseling) A
             dose of >/=1500 mg/day metformin is required for inclusion into the trial. The dosage
             needs to be stable for at least 8 weeks before randomisation. Patients with a total
             daily dose of less than 1500 mg metformin will only be included; if the investigator
             has documented them to be on their maximum tolerated dose (also in this case the 8
             week time interval will apply for a stable dose).

          2. Diagnosis of type 2 diabetes prior to informed consent

          3. Glycosylated haemoglobin A1 (HbA1c) at Visit 1a (Screening):

             For patients undergoing wash out of previous medication: HbA1c =7.0 to =9.5% For
             patients not undergoing wash-out of previous medication: HbA1c =7.0 to =10.0%

          4. Glycosylated haemoglobin A1 (HbA1c) =7.0 to =10.0% at Visit 2 (Start of Run-in)

          5. Age = 18 and < 80 years at Visit 1a (Screening)

          6. BMI (Body Mass Index) = 45 kg/m2 at Visit 1a (Screening)

          7. Signed and dated written informed consent by date of Visit 1a in accordance with GCP
             and local legislation

        Exclusion criteria:

          1. Myocardial infarction, stroke or TIA within 6 months prior to informed consent

          2. Impaired hepatic function, defined by serum levels of either Alanine
             transaminase,Aspartate transaminase, or alkaline phosphatase above 3 x upper limit of
             normal (ULN) as determined at Visit 1a

          3. Uncontrolled hyperglycaemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an
             overnight fast during wash-out / placebo run-in and confirmed by a second measurement
             (not on the same day).

          4. Known hypersensitivity or allergy to the investigational product or its excipients or
             metformin or placebo

          5. Treatment with rosiglitazone or pioglitazone within 3 months prior to informed consent

          6. Treatment with an injectable Glucagon-like peptide- 1 (GLP-1) analogue (e.g.
             exenatide) , Dipeptidyl-Peptidase 4 (DPP-IV) inhibitor within 3 months prior to
             informed consent

          7. Treatment with insulin within 3 months prior to informed consent

          8. Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, rimonabant) within 3
             months prior to informed consent.

          9. Alcohol abuse within the 3 months prior to informed consent that would interfere with
             trial participation or drug abuse

         10. Participation in another trial with an investigational drug within 2 months prior to
             informed consent

         11. 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 transdermal patch,
                  intra-uterine devices/systems (IUDs/IUSs), oral, implantable or injectable
                  contraceptives, sexual abstinence and vasectomised partner. No exception will be
                  made.

         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.

         13. Renal failure or renal impairment (serum creatinine =1.5 mg/dl as determined at Visit
             1a)

         14. Dehydration by clinical judgement of the investigator

         15. Unstable or acute congestive heart failure

         16. Acute or chronic metabolic acidosis (present in patient history)

         17. Hereditary galactose intolerance