Bioavailability of Empagliflozin/Metformin Fixed Dose Combinations (FDCs) in Healthy Chinese Volunteers

Study Overview
=================
Brief Summary
-----------------
The aim of the trial is to assess the relative bioavailability of fixed dose combination tablets of Empagliflozin and metformin compared to the administration of single tablets (Empagliflozin and metformin ) in Chinese subjects. The availability of a fixed dose combination tablet is expected to significantly enhance patient's compliance with antidiabetic treatment, in particular with concern to the frequent polypharmacy in diabetic patients.

Official Title
-----------------
Relative Bioavailability of Empagliflozin (12.5 or 5 mg)/Metformin (850 mg or 500 mg) Fixed Dose Combination Tablets Compared to Single Tablets Administered Together to Healthy Chinese Male and Female Volunteers in an Open-label, Randomised, Single-dose, Two-way Crossover Study

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: 5 mg empagliflozin/850 mg metformin FDC
* Drug: 12.5 mg empagliflozin
* Drug: 12.5 mg empagliflozin
* Drug: 850 mg metformin
* Drug: 5 mg empagliflozin
* Drug: 5 mg empagliflozin
* Drug: 850 mg metformin
* Drug: 12.5 mg empagliflozin/850 mg metformin FDC
* Drug: 12.5 mg empagliflozin/500 mg metformin FDC
* Drug: 5 mg empagliflozin/500 mg metformin FDC
* Drug: 500 mg metformin
* Drug: 500 mg metformin


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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12.5 mg empagliflozin/850 mg metformin<br>24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of 12.5 mg empagliflozin/850 mg metformin and single 10 mg empagliflozin, 2.5 mg empagliflozin, 850 mg metformin tablets single dose in randomized order | Drug: 12.5 mg empagliflozin<br>* 10mg empagliflozin tablet and 2.5 mg empagliflozin tablet<br>Drug: 850 mg metformin<br>* 850mg metformin tablet<br>Drug: 12.5 mg empagliflozin/850 mg metformin FDC<br>* 12.5 mg empagliflozin/850 mg metformin FDC<br>|
| Experimental: 5 mg empagliflozin/850 mg metformin<br>24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of 5 mg empagliflozin/850 mg metformin and single Empagliflozin(5mg) and metformin (850mg) tablets single dose in randomized order | Drug: 5 mg empagliflozin/850 mg metformin FDC<br>* 5 mg empagliflozin/850 mg metformin FDC<br>Drug: 5 mg empagliflozin<br>* 5 mg empagliflozin<br>Drug: 850 mg metformin<br>* 850 mg metformin<br>|
| Experimental: 12.5 mg empagliflozin/500 mg metformin<br>24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of 12.5 mg empagliflozin/500 mg metformin and single 10 mg empagliflozin, 2.5 mg empagliflozin, 500 mg metformin tablets single dose in randomized order | Drug: 12.5 mg empagliflozin<br>* 10 mg empagliflozin tablet and 2.5 mg empagliflozin tablet<br>Drug: 12.5 mg empagliflozin/500 mg metformin FDC<br>* 12.5 mg empagliflozin/500 mg metformin FDC<br>Drug: 500 mg metformin<br>* 500 mg metformin<br>|
| Experimental: 5 mg empagliflozin/500 mg metformin<br>24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of 5 mg empagliflozin/500 mg metformin and single Empagliflozin(5mg) and metformin (500mg) tablets single dose in randomized order | Drug: 5 mg empagliflozin<br>* 5 mg empagliflozin<br>Drug: 5 mg empagliflozin/500 mg metformin FDC<br>* 5 mg empagliflozin/500 mg metformin FDC<br>Drug: 500 mg metformin<br>* 500 mg metformin<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-∞) for Empagliflozin | Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| AUC(0-∞) for Metformin | Area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| Cmax for Empagliflozin | Maximum measured concentration of the empagliflozin in plasma | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| Cmax for Metformin | Maximum measured concentration of the metformin in plasma | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-tz) of Empagliflozin | Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 up to the last quantifiable data point | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration | 
| AUC(0-tz) of Metformin | Area under the concentration-time curve of the metformin in plasma over the time interval from 0 up to the last quantifiable data point | 1 hour (h) before drug administration and 20 min (m), 40m, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration |