Efficacy and Safety of Empagliflozin (BI 10773) / Linagliptin (BI 1356) Fixed Dose Combination in Treatment naïve and Metformin Treated Type 2 Diabetes Patients

Study Overview
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Brief Summary
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This trial will evaluate use of BI 10773/linagliptin once daily (qd) fixed dose combination (FDC) in treatment naïve and metformin treated patients with type 2 diabetes mellitus to support approval by regulatory authorities.

Official Title
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A Phase III Randomized, Double-blind, Parallel Group Study to Evaluate the Efficacy and Safety of Once Daily Oral Administration of BI 10773 25 mg/Linagliptin 5 mg and BI 10773 10 mg/Linagliptin 5 mg Fixed Dose Combination Tablets Compared With the Individual Components (BI 10773 25 mg, BI 10773 10 mg, and Linagliptin 5 mg) for 52 Weeks in Treatment naïve and Metformin Treated Patients With Type 2 Diabetes Mellitus With Insufficient Glycaemic Control

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: high dose FDC
* Drug: BI 10773 high dose
* Drug: high dose FDC placebo
* Drug: low dose FDC placebo
* Drug: high dose FDC placebo
* Drug: high dose FDC placebo
* Drug: low dose FDC placebo
* Drug: low dose FDC placebo
* Drug: high dose BI 10773 placebo
* Drug: low dose FDC
* Drug: high dose FDC placebo
* Drug: BI 10773 low dose
* Drug: high dose BI 10773 placebo
* Drug: high dose BI 10773 placebo
* Drug: linagliptin
* Drug: low dose FDC placebo
* Drug: linagliptin placebo
* Drug: BI 10773 low dose placebo
* Drug: linagliptin placebo
* Drug: low dose BI 10773 placebo
* Drug: linagliptin placebo
* Drug: high dose BI 10773 placebo
* Drug: BI 10773 low dose placebo
* Drug: low dose BI 10773 placebo
* Drug: linagliptin placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of type 2 diabetes mellitus prior to informed consent Male and female patients on diet and exercise regimen who are drug-naïve (defined as absence of any oral antidiabetic therapy, glucagon like peptide-1 analog or insulin for 12 weeks prior to randomization) or pre-treated with metformin (=1500 mg/day or on the maximum tolerated dose or the maximum dose according to local label) unchanged for 12 weeks prior to randomisation. Glycosylated hemoglobin (HbA1c) = 7.0% and = 10.5% (= 53.0 mmol/mol and = 91.3 mmol/mol) at Visit 1 (screening) Exclusion criteria: Uncontrolled hyperglycemia with a glucose level >240 mg/dl (>13.3 mmol/L) after an overnight fast during placebo run-in and confirmed by a second measurement (not on the same day). Any other antidiabetic drug within 12 weeks prior to randomization (except metformin background therapy as defined via inclusion criterion 2) Acute coronary syndrome (non-ST elevation myocardial infarction, ST elevation myocardial infarction and unstable angina pectoris), stroke or (transient ischemic attack) TIA within 3 months prior to informed consent

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: BI 10773/linagliptin FDC (high dose)<br>Patients receive BI 10773/linagliptin FDC (high dose) once daily | Drug: high dose FDC<br>* once daily<br>Drug: low dose FDC placebo<br>* once daily<br>Drug: high dose BI 10773 placebo<br>* once daily<br>Drug: BI 10773 low dose placebo<br>* once daily<br>Drug: linagliptin placebo<br>* once daily<br>|
| Experimental: BI 10773/linagliptin FDC (low dose)<br>Patients receive BI 10773/linagliptin FDC (low dose) once daily | Drug: high dose FDC placebo<br>* once daily<br>Drug: low dose FDC<br>* once daily<br>Drug: high dose BI 10773 placebo<br>* once daily<br>Drug: BI 10773 low dose placebo<br>* once daily<br>Drug: linagliptin placebo<br>* once daily<br>|
| Active Comparator: BI 10773 (high dose)<br>Patients receive BI 10773 (high dose) once daily | Drug: BI 10773 high dose<br>* once daily<br>Drug: high dose FDC placebo<br>* once daily<br>Drug: low dose FDC placebo<br>* once daily<br>Drug: low dose BI 10773 placebo<br>* once daily<br>Drug: linagliptin placebo<br>* once daily<br>|
| Active Comparator: BI 10773 (low dose)<br>Patients receive BI 10773 (low dose) once daily | Drug: high dose FDC placebo<br>* once daily<br>Drug: low dose FDC placebo<br>* once daily<br>Drug: high dose BI 10773 placebo<br>* once daily<br>Drug: BI 10773 low dose<br>* low dose once daily<br>Drug: linagliptin placebo<br>* once daily<br>|
| Active Comparator: Linagliptin<br>Patients receive linagliptin once daily | Drug: low dose FDC placebo<br>* once daily<br>Drug: high dose FDC placebo<br>* once daily<br>Drug: linagliptin<br>* once daily<br>Drug: high dose BI 10773 placebo<br>* once daily<br>Drug: low dose BI 10773 placebo<br>* once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Metformin Background Patients | Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage. | Baseline and 24 weeks | 
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) for Treatment Naive Patients | Glycosylated hemoglobin (HbA1c) is a measurement of the percentage of hemoglobin that is glycated. The change from baseline in HbA1c is calculated as the week 24 HbA1c minus the baseline HbA1c. Since HbA1c is measured as a percentage the change from baseline is also a percentage. | Baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose at Week 24 for Metformin Background Patients | Change from baseline in fasting plasma glucose at week 24 for Metformin Background patients. | Baseline and 24 Weeks | 
| Change From Baseline in Fasting Plasma Glucose at Week 24 for Treatment Naive Patients | Change from baseline in fasting plasma glucose at week 24 for Treatment Naive patients. | Baseline and 24 Weeks | 
| Change From Baseline in Body Weight for Metformin Background Patients | Change from baseline in body weight for Metformin Background patients. | Baseline and 24 Weeks | 
| Change From Baseline in Body Weight for Treatment Naive Patients | Change from baseline in body weight for Treatment Naive patients. | Baseline and 24 Weeks | 
| Occurrence of Treat to Target Efficacy Response for Metformin Background Patients | Occurrence of the treat-to-target efficacy response for Metformin Background patients measured as HbA1c < 7.0% after 24 weeks of treatment for patients with HbA1c >=7.0% at baseline. | 24 Weeks | 
| Occurrence of Treat to Target Efficacy Response for Treatment Naive Patients | Occurrence of the treat-to-target efficacy response for Treatment Naive patients measured as HbA1c < 7.0% after 24 weeks of treatment for patients with HbA1c >=7.0% at baseline. | 24 Weeks |