Bioequivalence of a FDC Tablet of Linagliptin/Metformin (2.5mg/1000mg) Extended Release in Healthy Subjects.

Study Overview
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Brief Summary
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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.

Official Title
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Bioequivalence of a Fixed Dose Combination Tablet of Linagliptin/Metformin Extended Release (2.5 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
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Healthy

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


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

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

What is the study measuring?
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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 the concentration-time curve of 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-tz (Area under the concentration-time curve of metformin 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 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 linagliptin 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 metformin 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 |