A Randomised, db, Placebo-controlled Study of BI 1356 for 18 Weeks Followed by a 34 Week Double-blind Extension Period (Placebo Patients Switched to Glimepiride) in Type 2 Diabetic Patients for Whom Treatment With Metformin is Inappropriate

Study Overview
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Brief Summary
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Efficacy of BI 1356 compared to placebo in patients for whom metformin therapy is inappropriate (intolerability, contraindication). The second part of the study looks at the safety of BI 1356 in this patient population with longer term treatment in comparison to a sulfonylurea drug (glimepiride)

Official Title
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A Randomised, db, Placebo-controlled, Parallel Group Efficacy and Safety Study of BI 1356 (5mg), Administered Orally Once Daily for 18 Weeks Followed by a 34 Week Double-blind Extension Period (Placebo Patients Switched to Glimepiride) in Type 2 Diabetic Patients With Insufficient Glycaemic Control for Whom Metformin Therapy is Inappropriate (Intolerability or Contraindication)

Conditions
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Diabetes Mellitus, Type 2

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients between 18 and 80 years old with type 2 diabetes and insufficient glycemic control (HbA1c 7% to 10%) for whom metformin therapy is inappropriate (intolerability or contraindication) Exclusion criteria Myocardial infarction, stroke or Transient ischaemic attack in last 6 months Treatment with rosiglitazone or pioglitazone, GLP-1 analogues, insulin or anti-obesity drugs in past 3 months Impaired hepatic function Severe renal impairment current treatment with systemic steroids change in dosage of thyroid hormones 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>52 week treatment | Drug: Linagliptin<br>* 5mg once daily<br>|
| Placebo Comparator: Placebo<br>First 18 weeks of treatment | Drug: Linagliptin Placebo<br>* 0 mg placebo comparator for part 1 of study (to 18 weeks)<br>|
| Active Comparator: Glimepiride<br>Placebo patients switch to glimepiride week19-52 | Drug: Glimepiride<br>* 1-4mg for part 2 of study (weeks 19-52)<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 18 (Interim Analysis) | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c, prior OADs and reason for metformin intolerance. | Baseline and week 18 | 
| HbA1c Change From Baseline at Week 18 (Final Analysis) | HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c, prior OADs and reason for metformin intolerance. HbA1c is measured as a percentage. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent. Means are adjusted for baseline HbA1c, prior OADs and reason for metformin intolerance. The primary analysis was re-run at the completion of the study in the final study report. | Baseline and week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Plasma Glucose (FPG) Change From Baseline at Week 18 (Interim Analysis) | This change from baseline reflects the Week 18 FPG minus the Week 0 FPG. Means are adjusted for baseline FPG, baseline HbA1c, prior OADs and reason for metformin intolerance (Interim Analysis). | Baseline and week 18 | 
| Percentage of Patients With HbA1c<7.0 at Week 18 (Interim Analysis) | Odds ratios are adjusted for baseline HbA1c, prior OADs and reason for metformin intolerance. | Week 18 | 
| Percentage of Patients With HbA1c<6.5 at Week 18 (Interim Analysis) | Odds ratios are adjusted for baseline HbA1c, prior OADs and reason for metformin intolerance. | Week 18 | 
| Percentage of Patients With HbA1c Lowering by 0.5% at Week 18 (Interim Analysis) | Odds ratios are adjusted for baseline HbA1c, prior OADs and reason for metformin intolerance. | Week 18 | 
| The Change in HbA1c From Baseline by Visit Over Time | HbA1c is measured as a percentage. Thus, this change from baseline reflects the HbA1c percent (at weeks 6, 12, 18, 22, 26, 30, 34, 40, 46, 52) minus the Week 0 HbA1c percent. | Baseline and weeks 6,12, 18, 22, 26, 30, 34, 40, 46, 52 | 
| The Change in FPG From Baseline by Visit Over Time | This change from baseline reflects the FPG (at weeks 6, 12, 18, 22, 26, 30, 34, 40, 46, 52) minus the Week 0 FPG. | Baseline and weeks 6,12,18, 22, 26, 30, 34, 40, 46, 52 |