Bioequivalence of a FDC Tablet of Linagliptin/Metformin (5mg/1000mg) Extended Release in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to demonstrate bioequivalence of a newly developed fixed dose combination (FDC) tablet containing linagliptin and metformin extended release compared to the free combination of linagliptin and metformin extended release, both under fed and fasted conditions.

Official Title
-----------------
Bioequivalence of a Fixed Dose Combination Tablet of Linagliptin/Metformin Extended Release (5 mg/1000 mg) Compared With the Free Combination of Linagliptin and Metformin Extended Release Tablets in Healthy Subjects (an Open-label, Randomised, Single Dose, Two-way Crossover Trial)

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

Intervention / Treatment
-----------------
* Drug: Linagliptin/Metformin ER FDC
* Drug: Linagliptin
* Drug: Metformin ER


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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 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: FDC first, fasted<br>Linagliptin/Metformin ER FDC followed by single tablets of linagliptin and metformin ER, fasted condition | Drug: Linagliptin/Metformin ER FDC<br>* 1x Linagliptin/Metformin FDC tablet<br>Drug: Linagliptin<br>* 1x Linagliptin tablet<br>Drug: Metformin ER<br>* 2x Metformin ER tablets<br>|
| Experimental: Single tablets first, fasted<br>single tablets of linagliptin and metformin ER followed by Linagliptin/Metformin ER FDC, fasted condition | Drug: Linagliptin/Metformin ER FDC<br>* 1x Linagliptin/Metformin FDC tablet<br>Drug: Linagliptin<br>* 1x Linagliptin tablet<br>Drug: Metformin ER<br>* 2x Metformin ER tablets<br>|
| Experimental: FDC first, fed<br>Linagliptin/Metformin ER FDC followed by single tablets of linagliptin and metformin ER, fed condition | Drug: Linagliptin/Metformin ER FDC<br>* 1x Linagliptin/Metformin FDC tablet<br>Drug: Linagliptin<br>* 1x Linagliptin tablet<br>Drug: Metformin ER<br>* 2x Metformin ER tablets<br>|
| Experimental: Single tablets first, fed<br>single tablets of linagliptin and metformin ER followed by Linagliptin/Metformin ER FDC, fed condition | Drug: Linagliptin/Metformin ER FDC<br>* 1x Linagliptin/Metformin FDC tablet<br>Drug: Linagliptin<br>* 1x Linagliptin tablet<br>Drug: Metformin ER<br>* 2x Metformin ER tablets<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) | AUC 0-72 (area under concentration-time curve of the Linagliptin in plasma from 0 to 72 hours) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration | 
| Maximum Measured Concentration of Linagliptin in Plasma (Cmax) | Cmax (maximum measured concentration of Linagliptin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration | 
| Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) | AUC 0-t (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration | 
| Cmax of Metformin in Plasma | Cmax (maximum measured concentration of the Metformin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf) | AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Linagliptin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration | 
| AUC0-inf of Metformin in Plasma | AUC0-inf(area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Metformin. The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively. | 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration |