Bioequivalence of a Fixed Dose Combination Tablet Linagliptin/Pioglitazone Compared With Its Mono-components

Study Overview
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Brief Summary
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The objective of the current study is to establish the bioequivalence of linagliptin/ pioglitazone fixed dose combination tablet compared to single tablets of linagliptin and pioglitazone administered together.

Official Title
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Bioequivalence of a Fixed Dose Combination Tablet of Linagliptin 5 mg / Pioglitazone 30 mg Compared With Its Mono-components in Healthy Male and Female Subjects (an Open-label, Randomised, Single-dose, Replicate Design Study With Two Treatments in Four Crossover Periods)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Linagliptin + Pioglitazone
* Drug: Linagliptin + Pioglitazone
* Drug: Linagliptin/Pioglitazone
* Drug: Linagliptin/Pioglitazone


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

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: 1 Linagliptin/Pioglitazone (Test)<br>Fixed-Dose-Combination-Tablet, oral administration with 240 mL water | Drug: Linagliptin/Pioglitazone<br>* Medium dose oral administration<br>|
| Experimental: 2 Linagliptin + Pioglitazone (Ref)<br>Tablets, oral administration with 240 mL water for each treatment | Drug: Linagliptin + Pioglitazone<br>* Medium doses, oral administration<br>|
| Experimental: 3 Linagliptin/Pioglitazone (Test)<br>Fixed-Dose-Combination-Tablet, oral administration with 240 mL water | Drug: Linagliptin/Pioglitazone<br>* Medium dose oral administration<br>|
| Experimental: 4 Linagliptin + Pioglitazone (Ref)<br>Tablets, oral administration with 240 mL water for each treatment | Drug: Linagliptin + Pioglitazone<br>* Medium doses, oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-72 of Linagliptin | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours | 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours) | 
| Cmax of Linagliptin | Maximum measured concentration of the analyte in plasma was measured. Adjusted by-treatment geometric mean and CV were reported. | 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours) | 
| AUC0-tz of Pioglitazone | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point | 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours) | 
| Cmax of Pioglitazone | Maximum concentration of the analyte in plasma was measured. Adjusted by-treatment geometric mean and CV were calculated. | 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-tz for Linagliptin | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point for Linagliptin | 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours) | 
| AUC0-∞ of Linagliptin | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to infinity (inf) for linagliptin | 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours) | 
| AUC0-∞ of Pioglitazone | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 hours extrapolated to inf for pioglitazone | 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours) | 
| Tmax for Linagliptin | Time from dosing to the maximum measured concentration of the analyte in plasma for Linagliptin | 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours) | 
| Tmax for Pioglitazone | Time from dosing to the maximum measured concentration of the analyte in plasma for pioglitazone | 0-72 hours (measurements at baseline, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 11, 12, 24, 48 and 72 hours) |