Bioequivalence of Empagliflozin and Metformin Given as a Fixed Dose Combination Compared to 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 fixed dose combination (FDC) tablets (containing medium dose empagliflozin/500 mg metformin [Test 1] and low dose empagliflozin/500 mg metformin [Test 2]) and of the single tablets (medium dose empagliflozin tablets + Glucophage® 500 mg tablet [Reference 1] and low dose empagliflozin tablet + Glucophage® 500 mg tablet [Reference 2]) when administered together after a high fat, high caloric meal. The assessment of safety and tolerability will be an additional objective of this trial.

Official Title
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Bioequivalence of Empagliflozin/Metformin (500 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: metformin (Glucophage®)
* Drug: metformin (Glucophage®)
* Drug: empagliflozin
* Drug: empagliflozin and metformin
* Drug: empagliflozin and metformin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male and female subjects Subjects must be able to understand and comply with study requirements Age 18 to 50 years Body mass index (BMI) 18.5 to 29.9 kg/m2 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: FDC empagliflozin dose 1 and metformin<br>fix dose combination tablet after intake of a high fat, high caloric meal | Drug: empagliflozin and metformin<br>* FDC tablet empagliflozin and metformin<br>|
| Active Comparator: empagliflozin dose 1 + metformin tablets<br>single tablets after intake of a high fat, high caloric meal | Drug: empagliflozin<br>* single tablet empagliflozin<br>Drug: metformin (Glucophage®)<br>* single tablet metformin<br>|
| Experimental: FDC empagliflozin dose 2 and metformin<br>fix dose combination tablet after intake of a high fat, high caloric meal | Drug: empagliflozin and metformin<br>* FDC tablet empagliflozin and metformin<br>|
| Active Comparator: empagliflozin dose 2 + metformin tablets<br>single tablets after intake of a high fat, high caloric meal | Drug: metformin (Glucophage®)<br>* single tablet metformin<br>Drug: empagliflozin<br>* single tablet empagliflozin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ for Empagliflozin | AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Empagliflozin | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake | 
| AUC0-∞ for Metformin | AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Metformin | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake | 
| Cmax for Empagliflozin | Cmax (maximum measured concentration of the analyte in plasma) for Empagliflozin | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake | 
| Cmax for Metformin | Cmax (maximum measured concentration of the analyte in plasma) for Metformin | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-tz for Empagliflozin | 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 | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake | 
| AUC0-tz for Metformin | 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 | 1hour (h) before drug intake and 20minutes (min),40min,1h,1h 30min,2h,2h 30min, 3h, 3h 30min, 4h, 5h, 6h, 8h,10h,12h,24h,34h,48h,72h after drug intake |