Rel. BA of Empagliflozin (BI 10773)/Linagliptin FDC Tbl, Comparison With Mono-components, With a Second FDC Tablet and Influence of Food

Study Overview
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Brief Summary
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The primary objective of the current study is to investigate the relative bioavailability of BI 10773 / linagliptin fixed dose combination tablet (formulation A1, Treatment A, Test) compared to BI 10773 given in free combination with linagliptin (Treatment B, Reference), both in the fasting state. All 42 subjects entered are planned to be included in this comparison. The secondary objective is to investigate the relative bioavailability of BI 10773 / linagliptin fixed dose combination tablet after administration of a standardised high fat, high caloric meal (formulation A1, Treatment C, Test) compared to BI 10773 / linagliptin fixed dose combination in the fasting state (formulation A1,Treatment A, Reference). Of the 42 subjects entered 18 subjects are planned to be included in this comparison. An additional objective is to investigate the relative bioavailability of a second formulation of the fixed dose combination tablet of BI 10773 / linagliptin (formulation A3,Treatment D, Test) compared to BI 10773 / linagliptin fixed dose combination tablet (formulation A1,Treatment A, Reference). Of the 42 subjects entered 24 subjects are planned to be included in this comparison.

Official Title
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Relative Bioavailability Investigations of a 25 mg BI 10773 / 5 mg Linagliptin Fixed Dose Combination (FDC) Tablet (Formulation A1) Including the Comparison With Its Mono-components, the Comparison With a Second FDC Tablet (Formulation A3), and the Investigation of Food (an Open-label, Randomised, Single Dose, Crossover, Phase I Trial in Healthy Male and Female Volunteers)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 10773/linagliptin
* Drug: BI 10773/linagliptin
* Drug: BI 10773/linagliptin SID
* Drug: BI 10773/linagliptin FDC


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: healthy male and female subjects

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: BI 10773/linagliptin FDC SID<br>medium single dose ofBI 10773/linagliptin FDC (Formulation A1) | Drug: BI 10773/linagliptin<br>* medium single dose of BI 10773/linagliptin FDC (Formulation A1)<br>|
| Experimental: BI 10773/linagliptin SID<br>medium single dose of mono components BI 10773/linagliptin | Drug: BI 10773/linagliptin SID<br>* medium single dose of mono components BI 10773/linagliptin<br>|
| Experimental: BI 10773/linagliptin FDC<br>medium single dose of BI 10773/linagliptin FDC (Formulation A1) after high fat, high caloric meal | Drug: BI 10773/linagliptin FDC<br>* medium single dose of BI 10773/linagliptin FDC (Formulation A1) after high fat, high caloric meal<br>|
| Experimental: BI 10773/linagliptin<br>medium single dose of BI 10773/linagliptin FDC (Formulation A3) | Drug: BI 10773/linagliptin<br>* medium single dose of BI 10773/linagliptin FDC (Formulation A3)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Empagliflozin: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin: Area Under the Curve 0 to 72 Hours (AUC0-72) | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Empagliflozin: Maximum Measured Concentration (Cmax) | Maximum measured concentration of empagliflozin (empa) in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin: Maximum Measured Concentration (Cmax) | Maximum measured concentration of linagliptin in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Empagliflozin Fed vs Fasted: Maximum Measured Concentration (Cmax) | Maximum measured concentration of empagliflozin (empa) in plasma, comparing fed with fasted. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Empagliflozin Fed vs Fasted: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin Fed vs Fasted: Maximum Measured Concentration (Cmax) | Maximum measured concentration of linagliptin in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin Fed vs Fasted: Area Under the Curve 0 to 72 Hours (AUC0-72) | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Empagliflozin Formulation Comparison: Maximum Measured Concentration (Cmax) | Maximum measured concentration of empagliflozin (empa) in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Empagliflozin Formulation Comparison: Area Under the Curve 0 to the Last Quantifiable Drug Plasma Concentration (AUC0-tz) | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the last quantifiable drug plasma concentration. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin Formulation Comparison: Maximum Measured Concentration (Cmax) | Maximum measured concentration of linagliptin in plasma. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin Formulation Comparison: Area Under the Curve 0 to 72 Hours (AUC0-72) | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 to 72 hours. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 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 |
| --- | --- | --- |
| Empagliflozin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | Time from last dosing to the maximum measured concentration of empagliflozin (empa) in plasma. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin: Time From Last Dosing to Maximum Measured Concentration (Tmax) | Time from last dosing to the maximum measured concentration of linagliptin in plasma | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Empagliflozin: 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. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Empagliflozin Fed vs Fasted: 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. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin Fed vs Fasted: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Empagliflozin Formulation Comparison: 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. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration | 
| Linagliptin Formulation Comparison: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of linagliptin in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the measured values show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 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. Time frame for adverse event was until the end-of-study examination. | Drug administration until next treatment period/end-of-study examination, up to 36 days |