Linagliptin Versus Placebo in Type 2 Diabetic Patients With Inadequate Glycaemic Control on Metformin in Combination With Pioglitazone

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

Official Title
-----------------
A Phase III, Randomised, Double Blind, Placebo Controlled Parallel Group Efficacy and Safety Study of Linagliptin 5 mg Administered Orally Once Daily Over 24 Weeks in Type 2 Diabetic Patients With Insufficient Glycaemic Control Despite a Therapy of Metformin in Combination With Pioglitazone

Conditions
-----------------
Diabetes Mellitus, Type 2

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Diagnosis of diabetes mellitus prior to informed consent Patients treated with metformin and pioglitazone (therapy should be unchanged for 12 weeks) Glycosylated haemoglobin A1 >= 7.5% and <= 10% Age between 18 and less than 80 - Body Mass index less or equal to 45 Exclusion criteria: Uncontrolled hyperglycaemia during run in period Myocardial infarction, stroke or transient ischaemic accident within 3 months prior to informed consent Impaired hepatic function Gastric by pass surgery Treatment with roziglitazone, GLP 1 analogues, DPP-4 inhibitors or insulin within 3 months prior to informed consent Treatment with anti-obesity drugs Current treatment with systemic steroids at the time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent Premenopausal 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 during the trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linagliptin<br>Linagliptin tablets once daily | Drug: Linagliptin<br>* Linagliptin tablets once daily<br>|
| Placebo Comparator: Placebo<br>Placebo tablets once daily | Drug: Placebo<br>* Placebo matching linagliptin tablets once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 24 Weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin | baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 6 Weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin | baseline, 6 weeks | 
| Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 12 Weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin | baseline, 12 weeks | 
| Change From Baseline in HbA1c (Glycosylated Hemoglobin) After 18 Weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin | baseline, 18 weeks | 
| Occurrence of Absolute Efficacy Response (HbA1c < 7%) After 24 Weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin | 24 weeks | 
| Occurrence of Absolute Efficacy Response (HbA1c < 6.5%) After 24 Weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin | 24 weeks | 
| Occurrence of Relative Efficacy Response (Reduction in HbA1c >= 0.5%) After 24 Weeks | Glycosylated hemoglobin is reported as a percentage of the total hemoglobin | 24 weeks | 
| Change From Baseline in Fasting Plasma Glucose (FPG) After 24 Weeks | Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 24 | baseline, 24 weeks | 
| Change From Baseline in Fasting Plasma Glucose (FPG) After 6 Weeks | Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 6 | baseline, 6 weeks | 
| Change From Baseline in Fasting Plasma Glucose (FPG) After 12 Weeks | Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 12 | baseline, 12 weeks | 
| Change From Baseline in Fasting Plasma Glucose (FPG) After 18 Weeks | Adjusted mean change in fasting plasma glucose (FPG) from baseline at week 18 | baseline, 18 weeks |