Efficacy and Safety of Linagliptin in Combination With Insulin 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 linagliptin (5 mg / once daily) compared to Placebo during long term treatment (52 weeks and longer) in combination with basal insulin in patients with type 2 diabetes mellitus with insufficient glycaemic control.

Official Title
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A Phase III Randomised, Double-blind, Placebo-controlled, Parallel Group Efficacy and Safety Study of Linagliptin (5 mg), Administered Orally Once Daily for at Least 52 Weeks in Type 2 Diabetic Patients in Combination With Basal Insulin Therapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Placebo
* Drug: Linagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diabetes type 2, detectable C-peptide, HbA1c 7-10% Pretreatment with basal insulin +/- Metformin or/and +/- Pioglitazone 3 Age > 18 years, BMI <= 45 kg/m2 Exclusion criteria: Uncontrolled hyperglycemia during Run-in Myocardial infarction, stroke or TIA within 3 months prior to informed consent Liver impairment; gastric surgery; medical history of cancer in last 5 years Other antidiabetic drugs, antiobesity drugs, systemic steroids, other investigational drug before randomisation Unsufficient birth control, pregnancy and nursing

Ages Eligible for Study
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Minimum Age: 18 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>patient receives a tablet with intended final marketed dose | Drug: Linagliptin<br>* intended final marketed dose<br>|
| Placebo Comparator: Placebo<br>patient receives a tablet identical to those containing Linagliptin | Drug: Placebo<br>* Placebo, identical to Linagliptin tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c After 24 Weeks | HbA1c is measured as a percentage. Adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant Oral antidiabetic drugs (OAD) | Baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With HbA1c < 7.0 Percent |  | 24 and 52 weeks | 
| Number of Patients Lowering HbA1c by at Least 0.5 Percent |  | 24 and 52 weeks | 
| Change From Baseline in HbA1c by Visit at Week 6 | Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs | Baseline and 6 weeks | 
| Change From Baseline in HbA1c by Visit at Week 12 | Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs | Baseline and 12 weeks | 
| Change From Baseline in HbA1c by Visit at Week 18 | Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs | Baseline and 18 weeks | 
| Change From Baseline in HbA1c by Visit at Week 32 | Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs | Baseline and 32 weeks | 
| Change From Baseline in HbA1c by Visit at Week 40 | Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs | Baseline and 40 weeks | 
| Change From Baseline in HbA1c by Visit at Week 52 | Means adjusted for treatment, baseline HbA1c, categorical renal function impairment and concomitant OADs | Baseline and 52 weeks | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at 24 Weeks of Treatment | Means adjusted for treatment, baseline HbA1c, baseline FPG, categorical renal function impairment and concomitant OADs | Baseline and 24 weeks | 
| Change From Baseline in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment |  | Baseline and 52 weeks | 
| Change From Baseline in FPG |  | Baseline, 6, 12, 18, 24, 32 and 40 weeks | 
| Change From Baseline in Mean Insulin Dose at 52 Weeks of Treatment | Means adjusted for treatment, continous baseline HbA1c, continous baseline weight, continous baseline Insulin, categorical renal function impairment and concomitant OADs | Baseline and 52 weeks | 
| Change From Baseline in Weighted Mean Daily Glucose After 24 and 52 Weeks of Treatment | Mean Daily Glucose was calculated using the 8-point blood glucose profile | Baseline, 24 and 52 weeks | 
| Change From Baseline in Incremental Post-prandial Glucose (iPPG) After 24 Weeks of Treatment |  | Baseline and 24 weeks: post-breakfast, post-lunch, post-dinner |