Safety and Efficacy in Type 2 Diabetic Patients With Severe Chronic Renal Impairment, 5 mg BI 1356 (Linagliptin) vs. Placebo, Insulin Background Inclusive

Study Overview
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Brief Summary
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to determine safety, efficacy and tolerability of BI 1356 versus placebo

Official Title
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Safety in Type 2 Diabetic Patients With Severe Chronic Renal Impairment, 5 mg BI 1356 vs. Placebo, DB, Parallel Group, Randomized, Insulin Background Inclusive

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: BI 1356
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male and female patients with type 2 diabetes and with glomerular filtration rate (GFR) <30 ml/min, who are not on chronic dialysis. Insufficient glycemic control (hemoglobin A1c (HbA1c) between 7.0% and 10.0%) Age 18 or over and not older than 80 years Exclusion criteria: Treatment with any other anti diabetic drug other than insulin and/or sulphonylurea within 3 months prior to informed consent Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent Unstable or acute congestive heart failure

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: BI 1356<br>patient to receive a tablet containing BI 1356 once daily | Drug: BI 1356<br>* BI 1356 dosed once daily<br>|
| Placebo Comparator: placebo<br>patient to receive a tablet identical to BI 1356 once daily | Drug: placebo<br>* placebo matching BI 1356 taken 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 Percent. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for baseline continuous HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Change From Baseline at Week 52 | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 52 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. | Baseline and Week 52 | 
| HbA1c Change From Baseline at Week 18 | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. | Baseline and Week 18 | 
| HbA1c Change From Baseline at Week 24 | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. | Baseline and Week 24 | 
| HbA1c Change From Baseline at Week 30 | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 30 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. | Baseline and Week 30 | 
| HbA1c Change From Baseline at Week 36 | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 36 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. | Baseline and Week 36 | 
| HbA1c Change From Baseline at Week 42 | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 42 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. | Baseline and Week 42 | 
| HbA1c Change From Baseline at Week 48 | HbA1c is measured as a Percent. Thus, this change from baseline reflects the Week 48 HbA1c percent minus the baseline HbA1c percent. Means are treatment adjusted for continuous baseline HbA1c , creatinine clearance at baseline and previous anti-diabetic medication. | Baseline and Week 48 | 
| The Occurrence of Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <6.5% After 52 Weeks of Treatment | The percentage of patients with an HbA1c value below 6.5% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). Analysis was only performed on patients with baseline HbA1c>=6.5% | Baseline and Week 52 | 
| The Occurrence of a Treat to Target Efficacy Response, That is an HbA1c Under Treatment of <7.0% After 52 Weeks of Treatment | The percentage of patients with an HbA1c value below 7.0% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). Analysis was only performed on patients with baseline HbA1c>=7%. | Baseline and Week 52 | 
| Percentage of Patients With HbA1c Lowering by 0.5% at Week 52 | The percentage of patients with an HbA1c reduction from baseline >=0.5% at week 52 was calculated for each treatment arm. Non-completers were imputed as failure (NCF). | Baseline and Week 52 | 
| 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 continuous baseline FPG , creatinine clearance , HbA1c and background of anti diabetic drugs | Baseline and Week 12 | 
| FPG Change From Baseline at Week 18 | Model includes treatment, continuous baseline FPG , creatinine clearance , HbA1c and background of anti diabetic drugs | 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 continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs | Baseline and Week 24 | 
| FPG Change From Baseline at Week 30 | This change from baseline reflects the week 30 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs | Baseline and Week 30 | 
| FPG Change From Baseline at Week 36 | This change from baseline reflects the week 36 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs | Baseline and Week 36 | 
| FPG Change From Baseline at Week 42 | This change from baseline reflects the week 42 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs | Baseline and Week 42 | 
| FPG Change From Baseline at Week 48 | This change from baseline reflects the week 48 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs | Baseline and Week 48 | 
| FPG Change From Baseline at week52 | This change from baseline reflects the week 52 FPG minus the baseline FPG. Means are treatment adjusted for continuous baseline FPG , baseline creatinine clearance , baseline HbA1c and background of anti diabetic drugs | Baseline and Week 52 | 
| Change From Baseline in Antidiabetic Background Therapy Dose at 52 Weeks Compared to Baseline and Over Time | Number of patients with at least one change in daily dose, determined by at least a 10% increase in insulin. | Baseline and Week 52 | 
| Clinically Relevant Drug-related Abnormalities for Blood Chemistry, Pulse Rate, Laboratory Parameters and ECG | Clinically relevant drug-related abnormalities for blood chemistry, pulse rate, laboratory parameters and ECG. New abnormal findings or worsening of baseline conditions were reported as adverse events. | first administration of randomised treatment to .... |