4 Week Treatment With Three Oral Doses of BI 10773 in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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Primary objective: safety and tolerability of BI 10773 in male and female patients with type 2 diabetes Secondary objective: pharmacokinetics and pharmacodynamics of BI 10773

Official Title
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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 4 Weeks Treatment With Three Oral Doses of BI 10773 as Tablets in Female and Male Patients With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: BI 10773 low dose
* Drug: placebo to BI 10773
* Drug: BI 10773 medium dose
* Drug: BI 10773 high dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and postmenopausal or hysterectomised female patients with type 2 diabetes Age >18 and < 70 years BMI >18.5 and <40 kg/m2 Exclusion Criteria: Antidiabetic treatment with insulin or glitazones or with more than one oral hypoglycaemic agent; Fasted blood glucose > 240 mg/dl (>13.3 mmol/L) or a blood glucose level above 400 mg/dl (22.2 mmol/L) postprandially; HbA1c > 8.5 %

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: placebo to BI 10773<br> <br> |
| Experimental: BI 10773 low dose<br> | Drug: BI 10773 low dose<br> <br> |
| Experimental: BI 10773 medium dose<br> | Drug: BI 10773 medium dose<br> <br> |
| Experimental: BI 10773 high dose<br> | Drug: BI 10773 high dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Drug Related Adverse Events | number of subjects with investigator-defined drug-related adverse events. | from drug administration up to 6 weeks | 
| Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinanalysis and ECG | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. | from drug administration up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Empagliflozin | maximum concentration of the analyte in plasma after first dose (Cmax, Day 1 ) and at steady state over a uniform dosing interval (Cmax,ss, Day 28). | 0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 hours(h) after drug administration on day 1 and 28 | 
| Tmax of Empagliflozin | time from last dosing to maximum concentration of the analyte in plasma after first dose (Day 1), denoted by tmax; and at steady state (Day 28), denoted by tmax,ss. | 0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1 and 28 | 
| t1/2 of Empagliflozin | terminal half-life of the analyte in plasma after first dose (Day 1), denoted by t1/2; and at steady state (Day 28), denoted by t1/2,ss. | 0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1 and 28 | 
| AUC0-∞ of Empagliflozin | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) and over a uniform dosing interval τ at steady state (AUCτ,ss) | 0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1 | 
| CL/F of Empaglifozin | apparent clearance of the analyte in plasma after first dose (CL/F) and at steady state (CL/F,ss) | 0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1 and 28 | 
| fe0-24 of Empagliflozin | Fraction of analyte eliminated in urine from time point 0 to 24h after first dose (fe0-24) and at steady state (fe0-24,ss) | 0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 24:00 h after drug administration on day 1 and 28 | 
| LI (Linearity Index). | The linearity index is defined as AUC0-τ divided by AUC0-∞ both at steady state. | 0:05 before drug administration and 0:15 0:30 0:45 1:00 1:30 2:00 2:30 3:00 4:00 6:00 8:00 10:00 12:00 16:00 after drug administration on day 1 and 28 | 
| Ae0-24 of Glucose | Amount of glucose eliminated in urine over the time interval 0 to 24h on day -2, -1, 1, 27 and 28. (Urinary Glucose Excretion) | Day -2 and 27: -2 to 0, 0 to 5, 5 to 12 and 12 to 24h; Day -1 and 1: 0 to 5, 5 to 12 and 12 to 24; Day 28: 0 to 5, 5 to 12, 12 to 24, 24 to 36, 36 to 48 and 48 to 72h | 
| Fasting Plasma Glucose (FPG) | fasting plasma glucose on day -1 (baseline) and change from baseline to day 28 | in the morning of days -1 and 28 | 
| Mean Daily Glucose (MDG) Measured in Blood | change from baseline in MDG on the days 1, 7, 14, 21 and 27. Baseline is defined as day -2. | 0:00, 2:30, 5:00, 7:00, 10:00, 12:00, 13:30, 24:00 h after drug administration on day -2. 0:05 h before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00, 13:30, 24:00 h after drug administration on day 1, 7, 14, 21 and 27 | 
| Insulin AUEC0-5 | change in AUEC0-5 from baseline on day 28. Baseline is defined as day -1. | 0:00, 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day -1. 0:05 before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day 28. | 
| Insulin Emax (Maximum Measured Effect) | change in Emax from baseline on day 28. Baseline is defined as day -1 | 0:00, 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day -1. 0:05 before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day 28. | 
| Fasting Insulin | Change from baseline to the days 1, 7, 14, 21 and 28. Baseline is defined as day -1. | in the morning of days -1( baseline), 1, 7, 14, 21 and 28 | 
| Glucagon Emax (Maximum Measured Effect) | Change from baseline (day -1) in Emax on day 28. | 0:00, 2:30, 5:00, 7:00, 10:00, 12:00, 24:00 h after drug administration on day -1. 0:05 before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day 28. | 
| Glucagon AUEC0-5 | Change from baseline (day -1) in AUEC0-5 on day 28. | 0:00, 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day -1. 0:05 before drug administration and 2:30, 5:00, 7:00, 10:00, 12:00 after drug administration on day 28. | 
| Fructosamine | change from baseline to days 14 and 18. Baseline is defined as day -1. | day -1 (baseline), 14 and 28 | 
| HbA1c | change from baseline on day 28. Baseline is defined as day -1. | in the morning of days -1 and 28 |