Drug Interaction Study With Dabigatran Etexilate and Dronedarone in Healthy Subjects

Study Overview
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Brief Summary
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The objective of the study is to assess the relative bioavailability of a single dose of dabigatran after concomitant multiple oral administration of dronedarone with the aim to investigate whether and to what extent the P-gp inhibitor dronedarone affects pharmacokinetic parameters of dabigatran when administered to healthy subjects

Official Title
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Relative Bioavailability of a Single Dose of 150 mg Dabigatran Etexilate (Capsule) When Administered Alone or in Combination With a Single Dose of 400 mg Dronedarone Tablet) or in Combination With 400 mg Bid Dronedarone (Tablet) at Steady State in Healthy Male and Female Volunteers (an Open Label, Randomised, Four-sequence, Two Period Cross-over, Phase I Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dabigatran etexilate plus dronedarone
* Drug: Dabigatran etexilate
* Drug: Dabigatran etexilate plus dronedarone
* Drug: Dabigatran etexilate plus dronedarone
* Drug: Dabigatran etexilate plus dronedarone


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 1. Healthy male and female subjects 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: A: Dabigatran alone (Reference)<br>Capsule, oral administration with 240 mL water | Drug: Dabigatran etexilate<br>* 150 mg as single dose<br>|
| Experimental: B: Dabigatran plus Dronedarone (Test)<br>Capsule and Tablets, oral administration with 240 mL water | Drug: Dabigatran etexilate plus dronedarone<br>* dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose<br>|
| Experimental: C: Dabigatran plus Dronedarone (Test)<br>Capsule and Tablets, oral administration with 240 mL water | Drug: Dabigatran etexilate plus dronedarone<br>* dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose (staggered administration)<br>|
| Experimental: D: Dabigatran plus Dronedarone (Test)<br>Capsule and Tablets, oral administration with 240 mL water | Drug: Dabigatran etexilate plus dronedarone<br>* dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid<br>|
| Experimental: E: Dabigatran plus Dronedarone (Test)<br>Capsule and Tablets, oral administration with 240 mL water | Drug: Dabigatran etexilate plus dronedarone<br>* dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid (staggered administration)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity. | 1 h before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00 h after drug administration | 
| Total Dabigatran: Maximum Measured Concentration (Cmax) | Maximum measured concentration of total dabigatran in plasma, per period. | 1 h before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00 h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞) | Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity. | 1 h before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00 h after drug administration | 
| Free Dabigatran: Maximum Measured Concentration (Cmax) | Maximum measured concentration of free dabigatran in plasma, per period. | 1 h before drug administration and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00 h after drug administration |