Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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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 patients with type 2 diabetes mellitus with insufficient glycaemic control

Official Title
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A Randomised, Double-blind, Placebo-controlled Parallel Group Efficacy and Safety Study of BI 1356 (One Dose, e.g. 5 mg), Administered Orally Once Daily Over 24 Weeks, With an Open Label Extension to 80 Weeks (Placebo Patients Switched to BI 1356), in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite Metformin Therapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: linagliptin
* Drug: linagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 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 Diagnosis of type 2 diabetes prior to informed consent Glycosylated haemoglobin A1 (HbA1c)at screening: For patients undergoing wash out of previous medication: HbA1c 6.5 - 9.0% For patients not undergoing wash-out of previous medication: HbA1c 7.0 - 10.0% Glycosylated haemoglobin A1 (HbA1c) 7.0 - 10.0% at the beginning of Placebo Run-in Age 18 -80 years BMI (Body Mass Index) less than 40 kg/m2 Signed and dated written informed consent by date of Visit 1a in accordance with GCP and local legislation Exclusion criteria: Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent Impaired hepatic function Known hypersensitivity or allergy to the investigational product or its excipients or metformin or placebo Treatment with rosiglitazone or pioglitazone within 3 months prior to informed consent Treatment with an injectable GLP-1 analogue (e.g. exenatide) within 3 months prior to informed consent Treatment with insulin within 3 months prior to informed consent Treatment with anti-obesity drugs (e.g. sibutramine, orlistat, rimonabant) within 3 months prior to informed consent Alcohol abuse within the 3 months prior to informed consent that would interfere with trial participation or drug abuse Participation in another trial with an investigational drug within 2 months prior to informed consent Pre-menopausal women 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. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent. Renal failure or renal impairment Unstable or acute congestive heart failure Acute or chronic metabolic acidosis (present in patient history) Hereditary galactose intolerance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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<br>Patients receive linagliptin 5 mg tablets once daily | Drug: linagliptin<br>* Patients receive linagliptin 5 mg tablets once daily<br>|
| Placebo Comparator: Placebo<br>Patients receive placebo tablets matching linagliptin 5 mg tablets once daily | Drug: linagliptin<br>* Patients receive linagliptin 5 mg 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 24 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication. | Baseline and week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Change From Baseline at Week 6 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 6 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication. | Baseline and week 6 | 
| 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 baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication. | Baseline and week 12 | 
| HbA1c Change From Baseline at Week 18 | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline HbA1c and previous anti-diabetic medication. | Baseline and week 18 | 
| FPG Change From Baseline at Week 24 | This change from baseline reflects the Week 24 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication. | Baseline and week 24 | 
| FPG Change From Baseline at Week 6 | This change from baseline reflects the Week 6 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication. | Baseline and week 6 | 
| 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 | 
| FPG Change From Baseline at Week 18 | This change from baseline reflects the Week 18 FPG minus the baseline FPG. Means are treatment adjusted for baseline HbA1c, baseline FPG and previous anti-diabetic medication. | Baseline and week 18 | 
| Percentage of Patients With HbA1c <7.0% at Week 24. | The percentage of patients with an HbA1c value below 7.0% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c >= 7.0%. Only patients with baseline HbA1c >= 7% | Baseline and week 24 | 
| Percentage of Patients With HbA1c < 7.0% at Week 24 | The percentage of patients with an HbA1c value below 7.0% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c >= 7.0%. | Baseline and week 24 | 
| Percentage of Patients With HbA1c <6.5% at Week 24 | The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c >= 6.5%. Only patients with baseline HbA1c >= 6.5% | Baseline and week 24 | 
| Percentage of Patients With HbA1c<6.5% at Week 24 | The percentage of patients with an HbA1c value below 6.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c >= 6.5%. | Baseline and week 24 | 
| Percentage of Patients Who Have a HbA1c Lowering by 0.5% at Week 24 | The percentage of patients with an HbA1c reduction from baseline >= 0.5% at week 24 was calculated for each treatment arm. If a patient did not have an HbA1c value at week 24 they were considered a failure, so HbA1c reduction less than 0.5%. | Baseline and week 24 | 
| Adjusted Means for 2h Post Prandial Blood Glucose (PPG) Change From Baseline at Week 24 | This change from baseline reflects the Week 24 2h PPG minus the baseline 2h PPG. Means are treatment adjusted for baseline HbA1c, baseline PPG and previous anti-diabetic medication. | Baseline and week 24 | 
| 2 Hour Post-Prandial Glucose (PPG) Increment Over Fasting Plasma Glucose (FPG) at Week 24 | This change from baseline reflects the Week 24 (2h PPG - FPG) minus the baseline (2h PPG - FPG). Means are treatment adjusted for baseline HbA1c, baseline 2h PPG increment over FPG and previous anti-diabetic medication. | Baseline and week 24 |