Relative Bioavailability of 2 Fixed Dose Combinations of Empagliflozin/Metformin Extended Release (XR) Compared With Single Tablets

Study Overview
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Brief Summary
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The purpose of this trial is to demonstrate the relative bioavailability of 2 newly developed fixed dose combinations (FDC) tablets containing empagliflozin & metformin XR and the single tablets of empagliflozin and metformin XR when administered singularly

Official Title
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Relative Bioavailability of Two Newly Developed FDC Tablet Strengths (10 mg/1000 mg and 5mg/750mg) of Empagliflozin/Metformin Extended Release Compared With the Free Combination of Empagliflozin and Metformin Extended Release in Healthy Subjects (an Open-label, Randomised, Single Dose, Two-way Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: 1 tablet Empagliflozin/2 tablets Metformin XR
* Drug: 10 mg Empagliflozin/1000 mg Metformin XR
* Drug: 1 tablet 10 mg Empagliflozin/3 tablets Metformin XR
* Drug: 2 tablets 5 mg Empagliflozin/750 Metformin XR
* Drug: 1 tablet Empagliflozin/2 tablets Metformin XR
* Drug: 10 mg Empagliflozin/1000 mg Metformin XR


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy males or females Age 18-50 years (incl.) Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.) Subjects must be able to understand and comply with study requirements Exclusion criteria: Any deviation from healthy condition

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: High dose, fasted<br>1 fixed dose combination (FDC) tablet vs 3 single tablets under fasted conditions | Drug: 10 mg Empagliflozin/1000 mg Metformin XR<br>* Experimental: high dose Empagliflozin/Metformin XR, FDC tablet<br>Drug: 1 tablet Empagliflozin/2 tablets Metformin XR<br>* Active Comparator: 1 x Empagliflozin/2x Metformin XR tablets<br>|
| Experimental: High dose, fed<br>1 fixed dose combination (FDC) tablet vs 3 single tablets under fed conditions | Drug: 1 tablet Empagliflozin/2 tablets Metformin XR<br>* Active Comparator: 1 x Empagliflozin/2x Metformin XR tablets<br>Drug: 10 mg Empagliflozin/1000 mg Metformin XR<br>* Experimental: high dose Empagliflozin/Metformin XR, FDC tablet<br>|
| Experimental: Low dose, fasted<br>2 fixed dose combination (FDC) tablets vs 4 single tablets under fasted conditions | Drug: 1 tablet 10 mg Empagliflozin/3 tablets Metformin XR<br>* Active Comparator: 1 x Empagliflozin/3 x Metformin XR tablets<br>Drug: 2 tablets 5 mg Empagliflozin/750 Metformin XR<br>* Experimental:2 x low dose Empagliflozin/Metformin XR FDC tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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), for Empagliflozin | Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz). | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 20min, 1h 40min, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration | 
| 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) for Metformin | Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 20min, 1h 40min, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration | 
| Cmax (Maximum Measured Concentration of the Analyte in Plasma, for Empagliflozin | Maximum measured concentration of empagliflozin in plasma (Cmax). | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 20min, 1h 40min, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration | 
| Cmax (Maximum Measured Concentration of the Analyte in Plasma, for Metformin | Maximum measured concentration of metformin in plasma | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 20min, 1h 40min, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity), for Empagliflozin | Area under the concentration-time curve of empagliflozin in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity). | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 20min, 1h 40min, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration | 
| AUC0-infinity (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity), for Metformin | Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 20min, 1h 40min, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 16h, 24h, 36h, 48h and 72h after drug administration |