BI 10773 add-on to Metformin 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 pharmacokinetics of five doses of BI 10773 compared to placebo given for 12 weeks as add-on therapy to on going metformin therapy in patients with T2DM with insufficient glycemic control. In addition, there will be an open-label treatment arm with sitagliptin (JanuviaTM) as add-on therapy to metformin.

Official Title
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A Phase II, Randomized, Parallel Group Safety, Efficacy, and Pharmacokinetics Study of BI 10773 (1 mg, 5 mg, 10 mg, 25 mg, and 50 mg) Administered Orally Once Daily Over 12 Weeks Compared Double Blind to Placebo With an Additional Open-label Sitagliptin Arm in Type 2 Diabetic Patients With Insufficient Glycemic Control Despite Metformin Therapy

Conditions
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Diabetes Mellitus, Type 2

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


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 and previously treated with metformin alone or with metformin and one other oral antidiabetic drug Stable metformin therapy of at least 1500 mg/day, or less if that is a maximum tolerated dose. HbA1c at screening 6.5% to 9.0% for patients on metformin and one other antidiabetic drug, and HbA1c >7.0% to 10% for patients on metformin only HbA1c >7.0% to 10.0% at Visit 2 (Start of Run-in) Age >=18 and <80years Body Mass Index (BMI) <=40 kg/m2 Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation Exclusion Criteria: Myocardial infarction, stroke or transient ischemic attack (TIA) within 6 months prior to informed consent Impaired hepatic function Renal insufficiency or impaired renal function Diseases of the central nervous system or psychiatric disorders or clinically relevant neurological disorders that may interfere with participation in the trial Chronic or clinically relevant acute infections Current or chronic urogenital tract infection History of clinically relevant allergy/hypersensitivity Treatment with glitazones (e.g., rosiglitazone, pioglitazone), glucagon-like peptide (GLP-1) analogues, or insulin within 3 months prior to informed consent Treatment with anti-obesity drugs within 3 months prior to informed consent Treatment with systemic steroids or change in dosage of thyroid hormones within 6 weeks prior to informed consent Alcohol abuse or drug abuse Treatment with an investigational drug within 2 months prior to informed consent Women of child-bearing potential who are nursing or pregnant, or who are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the study and do not agree to periodic pregnancy testing during participation in the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: sitagliptin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c After 12 Weeks of Treatment | Change from baseline in HbA1c after 12 weeks of treatment. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group. | 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. In the measured values adjusted means are displayed. For means for the placebo and empagliflozin arms are from the model excluding the sitagliptin open label (OL) arm. The mean for the sitagliptin OL arm is from the model with just this treatment group and the placebo group. | 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%) based on logistic regression | Baseline and 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%) based on logistic regression | Baseline and 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), FPG in mg/dl. 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) trough concentrations of Empagliflozin in plasma, within 30 minutes of dosing. | Days 28, 56 and 84 |