BI 1356 (Linagliptin) in Combination With Metformin and a Sulphonylurea in Type 2 Diabetes

A Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 (5 mg) Administered Orally Once Daily Over 24 Weeks, With an Open-label Extension to One Year (Placebo Patients Switched to BI 1356), in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite a Therapy of Metformin in Combination With a Sulphonylurea

The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (5 mg once daily) compared to placebo given for 24 weeks as add-on therapy to metformin in combination with a sulphonylurea in patients with type 2 diabetes mellitus with insufficient glycaemic control.

Inclusion criteria:

1. Male and female patients with a diagnosis of type 2 diabetes mellitus, currently treated only with a stable total daily dose of preferably* >/= 1500 mg metformin and a dose of a sulphonylurea drug that has been documented, by the Investigator, to be the individual maximum tolerated dose of that sulphonylurea drug. Both the dose and dosing regimen of metformin and the sulphonylurea must be stable (i.e. unchanged) for 10 weeks prior to informed consent, and must not be changed for the duration of the trial
2. Glycosylated haemoglobin A1 (HbA1c) >/= 7.0 and </= 10.0% at the screening Visit 1a and at Visit 2 (start of placebo run-in phase)
3. Age >/= 18 and </= 80 years at Visit 1a (screening)
4. BMI (Body Mass Index) </= 40 kg/m2 at Visit 1a (screening)
5. Signed and dated written informed consent, at the latest by the date of Visit 1a, in accordance with GCP and local legislation *Patients currently treated with a total daily dose of less than 1500 mg metformin can be included in the trial if the Investigator has documented that the dose is the maximum tolerated dose of metformin for that patient.

Exclusion criteria:

1. Myocardial infarction, stroke or TIA (transient ischaemic attack) within 6 months prior to the date of informed consent

2. Impaired hepatic function, defined by serum levels of either alanine transaminase (ALT/SGPT), aspartase transaminase (AST/SGOT), or alkaline phosphatase (ALP) above 3 times the upper limit of normal (ULN), as determined at Visit 1a

3. Renal failure or renal impairment (serum creatinine >/= 1.5 mg/dl) as determined at Visit 1a

4. Treatment with rosiglitazone or pioglitazone within 3 months prior to the date of informed consent

5. Treatment with GLP-1 analogues (e.g. exenatide) within 3 months prior to the date of informed consent

6. Treatment with insulin within 3 months prior to the date of informed consent

7. Treatment with anti-obesity drugs (e.g. sibutramine, rimonabant, orlistat) within 3 months prior to the date of informed consent

8. Current treatment with systemic steroids (i.e. at the time of informed consent) or a change in the dosage of thyroid hormones within 6 weeks prior to the date of informed consent

9. Pre-menopausal women (last menstruation </= 1 year prior to the date of 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 periodic pregnancy testing during their 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.

10. Known hypersensitivity or allergy to the investigational product or its excipients or to the trial background therapy (i.e. metformin in combination with a sulphonylurea) or sulphonamides

11. Dehydration (as confirmed by the Investigators clinical opinion)

12. Current acute or chronic metabolic acidosis