Bioavailability of a Fixed Dose Combination Tablet With Empagliflozin (BI 10773) and Metformin Compared With the Monocomponents and Effect of Food on Bioavailability

Study Overview
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Brief Summary
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The objective of the current study is to determine the relative bioavailability of a BI 10773 / metformin fixed dose combination tablet compared to single tablets of BI 10773 and metformin when administered together and to assess the effect of food on the bioavailability the fixed dose combination tablet

Official Title
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Relative Bioavailability of a 12.5 mg BI 10773 / 1000 mg Metformin Fixed Dose Combination Tablet Compared With Its Monocomponents and Administered With and Without Food (an Open-label, Randomised, Single-dose, Three-way Crossover, Phase I Trial in Healthy Volunteers)

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: C: BI 10773 / metformin tablet
* Drug: B: BI 10773 tablet and metformin tablet
* Drug: A: BI 10773 / metformin tablet


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy males and females according to the following criteria Body Mass Index 18.5 to 29.9 kg/m2 (incl.) Exclusion criteria: Any finding of the medical examination (including Blood Pressure, Pulse Rate and electrocardiogram) deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>3 treatments will be investigated in randomized order | Drug: A: BI 10773 / metformin tablet<br>* BI 10773 / metformin fixed dose combination tablet in fasted state<br>|
| Experimental: B<br>3 treatments will be investigated in randomized order | Drug: B: BI 10773 tablet and metformin tablet<br>* BI 10773 and metformin single tablets, administered together in fasted state<br>|
| Experimental: C<br>3 treatments will be investigated in randomized order | Drug: C: BI 10773 / metformin tablet<br>* BI 10773 / metformin fixed dose combination tablet after a high fat, high caloric meal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. Note the standard deviation is actually the coefficient of variation (CV). | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Empa: Maximum Measured Concentration (Cmax) | Maximum measured concentration of empagliflozin (empa) in plasma. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Metformin: Maximum Measured Concentration (Cmax) | Maximum measured concentration of metformin in plasma. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the time of the last quantifiable data point. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable data point. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Time to Maximum Measured Concentration (Tmax) | Time from dosing to the maximum concentration of the analyte in plasma. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Terminal Elimination Rate Constant in Plasma (λz) | Terminal elimination rate constant in plasma. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Terminal Half-life in Plasma (T1/2) | Terminal half-life of the analyte in plasma. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Mean Residence Time in the Body After Oral Administration (MRTpo) | Mean residence time of the analyte in the body after oral administration. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Apparent Clearance After Extravascular Administration (CL/F) | Apparent clearance of the analyte in the plasma after extravascular administration. Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Apparent volume of distribution during the terminal phase (λz). Note the standard deviation is actually the CV. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator. | Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events. | Drug administration up to 7 days after last drug administration, up to 8 days |