Demonstration of Bioequivalence of Empagliflozin and Metformin Given in One Tablet Compared to the Intake of Single Tablets

Study Overview
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Brief Summary
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The primary objective of this trial is to establish bioequivalence of two FDC tablets and the single tablets when administered together after a high fat high caloric meal.

Official Title
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Bioequivalence of Empagliflozin/Metformin (850 mg) Fixed Dose Combination Tablets Compared to Single Tablets Administered Together in Healthy Male and Female Volunteers Under Fed Conditions (an Open-label, Randomised, Single-dose, Four-way Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Empagliflozin
* Drug: Empagliflozin + Metformin
* Drug: Metformin
* Drug: Metformin
* Drug: Empagliflozin + Metformin
* Drug: Empagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 1. Healthy male and female subjects Exclusion criteria: 1. Any relevant deviation from healthy conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Test 1<br>fixed dose combination tablet | Drug: Empagliflozin + Metformin<br>* fixed dose combination tablet (low)<br>|
| Active Comparator: Reference 1<br>empagliflozin tablets and metformin tablet | Drug: Empagliflozin<br>* empagliflozin tablets and metformin tablet<br>Drug: Metformin<br>* empagliflozin tablets and metformin tablet<br>|
| Experimental: Test 2<br>fixed dose combination tablet | Drug: Empagliflozin + Metformin<br>* fixed dose combination tablet (low)<br>|
| Active Comparator: Reference 2<br>empagliflozin tablet and metformin tablet | Drug: Metformin<br>* empagliflozin tablet and metformin tablet<br>Drug: Empagliflozin<br>* empagliflozin tablet and metformin tablet<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 the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the Measured values shows 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 and 72h after drug administration | 
| Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. In this endpoint, the Measured values shows 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 and 72h after drug administration | 
| Empa: Maximum Measured Concentration (Cmax) | Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the Measured values shows 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 and 72h after drug administration | 
| Metformin: Maximum Measured Concentration (Cmax) | Maximum measured concentration of the analyte in plasma, per period. In this endpoint, the Measured values shows 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 and 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 the analyte in plasma over the time interval from 0 to the last quantifiable data point. In this endpoint, the Measured values shows 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 and 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 the analyte in plasma over the time interval from 0 to the last quantifiable data point. In this endpoint, the Measured values shows 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 and 72h after drug administration |