12 Weeks Treatment With 3 Different Doses of BI 10773 in Type 2 Diabetic Patients

Study Overview
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Brief Summary
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The objective is to investigate the efficacy, safety and pharmacokinetics of three different doses of BI 10773 compared to placebo given for 12 weeks in patients with type 2 diabetes mellitus with insufficient glycemic control. In addition an open-label metformin arm will be assessed

Official Title
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A Phase IIb, Randomized, Parallel Group Safety, Efficacy, and Pharmacokinetics Study of BI 10773 (5 mg, 10 mg and 25 mg) Administered Orally Once Daily Over 12 Weeks Compared Double Blind to Placebo, as Monotherapy, With an Additional Open-label Metformin Arm in Type 2 Diabetic Patients With Insufficient Glycemic Control

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: BI 10773
* Drug: placebo
* Drug: metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients with a diagnosis of type 2 diabetes mellitus either treatment-naïve or on a maximum of 1 oral antidiabetic therapy on a stable dose for the10 weeks prior to screening HbA1c ≥6.5 to ≤9.0% and for treatment-naïve patients:HbA1c >7.0 to ≤10.0% HbA1c >7.0 to ≤10.0% at Visit 2 (start of run-in) for all patients Age between 18 and 80 years BMI less than 40 kg/m2 Signed and dated informed consent prior to admission to the study in accordance with GCP and local legislation Exclusion Criteria: Myocardial infarction, stroke or TIA within 6 months prior to informed consent Impaired hepatic function Renal insufficiency or impaired renal function Disease of central nervous system, or psychiatric disorders or clinically relevant neurologic disorders that may interfere with trial participation Chronic or clinically relevant acute infections Current or chronic urogenital tract infection determined by medical history History of clinically relevant allergy/hypersensitivity Treatment with glitazones, GLP-1 analogues or insulin within 3 months prior to informed consent Treatment with anti obesity drugs Current treatment with systemic steroids Alcohol abuse Treatment with an investigational drug within 2 months prior to informed consent known intolerance to metformin Dehydration Unstable or acute CHF Acute or chronic acidosis Hereditary galactose intolerance Woman of child bearing potential who are nursing or pregnant or not practicing an acceptable method of birth control

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
Intervention Model: Parallel Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: BI 10773|nan|
|Drug: placebo|nan|
|Drug: metformin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Glycosilated Haemoglobin A1c (HbA1c) From Baseline After 12 Weeks of Treatment | Change of HbA1c from baseline after 12 weeks of treatment. Note, adjusted means are presented. For the placebo and empa groups, measured values presented are for the model including only these treatment groups, for the metformin group the measured values presented are for the model including only placebo and metformin groups. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of FPG From Baseline After 12 Weeks of Treatment | Change of Fasting Plasma Glucose (FPG) from baseline after 12 weeks of treatment. Results presented stem from a repeated measures analysis. Note, adjusted means are presented. For the placebo and empa groups, measured values presented are for the model including only these treatment groups, for the metformin group the measured values presented are for the model including only placebo and metformin groups. | Baseline and 12 weeks | 
| Change of HbA1c From Baseline Over Time | Change of HbA1c from baseline over time. Results presented stem from a repeated measures analysis. | Baseline and weeks 4, 8 and 12 | 
| Proportion of Patients Who Achieve an HbA1c ≤7.0% After 12 Weeks of Treatment | Results for HbA1c categories at week 12 (Proportion of patients with HbA1c less than equal to 7%). | 12 weeks | 
| Proportion of Patients Who Achieve an HbA1c Lowering of at Least 0.5% After 12 Weeks of Treatment | Results for HbA1c categories at week 12 (Proportion of patients with HbA1c lowered at least 0.5%). | 12 weeks | 
| Change From Baseline to Week 12 in Fasting Plasma Insulin (FPI) | Results for change of FPI from baseline at week 12 based on ANCOVA. | Baseline and 12 weeks | 
| Change in Homeostasis Model Assessment Index for Insulin Resistance (HOMA-IR) | HOMA-IR (to assess insulin resistance) is defined as (FPI x FPG)/22.5. Results based on ANCOVA. | Baseline and 12 weeks | 
| Change in Homeostasis Model Assessment Index for Beta Cell Function (HOMA-%B) | HOMA-%B (to assess insulin beta cell function) is defined as (20 x FPI)/(FPG-3.5). Results are based on ANCOVA. | Baseline and 12 weeks | 
| Change of Body Weight After 12 Weeks of Treatment | Results for change of body weight after 12 weeks of treatment based on ANCOVA. | Baseline and 12 weeks | 
| Trough Concentrations of Empagliflozin in Plasma | Pre-dose (within 30 minutes before dosing) trough concentrations of Empagliflozin in plasma | Days 28, 56 and 84 |