Efficacy and Safety of BI 1356 BS (Linagliptin) in Combination With Metformin in Patients With type2 Diabetes

Study Overview
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Brief Summary
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The objective of the study is to test the efficacy, safety and tolerability of several doses of BI 1356 BS (1, 5, or 10 mg taken once daily) compared to placebo given for 12 weeks together with metformin in patients with type 2 diabetes mellitus who are not at goal with their HbA1c levels. In addition, there will be an unblinded treatment arm with glimepiride as add-on therapy to metformin for comparison. The influence of several factors (gender, age, weight, race, etc.) on the bioavailability and efficacy of BI 1356 BS will also be tested in this study.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Five Parallel Groups Study Investigating the Efficacy and Safety of BI 1356 BS (1 mg, 5 mg and 10 mg Administered Orally Once Daily) Over 12 Weeks as add-on Therapy in Patients With Type 2 Diabetes and Insufficient Glycaemic Control Despite Metformin Therapy, Including an Open-label Glimepiride Treatment Arm.

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Linagliptin
* Drug: Linagliptin
* Drug: Linagliptin
* Drug: Placebo
* Drug: Glimepiride


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Inclusion_Criteria: Male and female patients with a diagnosis of type 2 diabetes mellitus and previo usly treated with metformin alone or with metformin and one other oral antidiabetic d rug HbA1c 7.0 9.0% at screening for patients treated with metformin and one other oral antidiabetic drug HbA1c 7.5 10.0% at screening for patients treated with metformin alone HbA1c 7.5 10.0% at beginning of the placebo run-in phase Age > 21 and < 75 years MI > 25 and < 40 kg/m2 (Body Mass Index) Exclusion criteria: Exclusion_Criteria: Clinically relevant cardiovascular disease Impaired hepatic function Renal insufficiency or impaired renal function Treatment with rosiglitazone or pioglitazone within 6 months prior to screening Treatment with insulin within 3 months prior to screening

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linagliptin low dose<br>Patients receive Linagliptin low dose tablets once daily | Drug: Linagliptin<br>* Linagliptin low dose tablet once daily<br>|
| Experimental: Linagliptin medium dose<br>Patients receive Linagliptin medium dose tablets once daily | Drug: Linagliptin<br>* Linagliptin medium dose tablet once daily<br>|
| Experimental: Linagliptin high dose<br>Patients receive Linagliptin high dose tablets once daily | Drug: Linagliptin<br>* Linagliptin high dose tablet once daily<br>|
| Placebo Comparator: Placebo<br>Patients receive tablets identical to those containing Linagliptin low, medium and high dose | Drug: Placebo<br>* Placebo tablets once daily<br>|
| Active Comparator: Glimepiride<br>Patients receive Glimepiride tablets once daily | Drug: Glimepiride<br>* Glimepiride tablets once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Change From Baseline at Week 12 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the HbA1c percent baseline value. Means are treatment adjusted for baseline HbA1c. | Baseline and week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With HbA1c<=7.0% at Week 12 | Descriptive calculation of Patients with HbA1c <= 7.0% at Week 12. | week 12 | 
| Fasting Blood Plasma Glucose Level (FPG) Change From Baseline at Week 12 | This change from baseline reflects the Week 12 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication. | Baseline and week 12 |