Drug Interaction Study With Dabigatran Etexilate and Dronedarone in Healthy Subjects

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)

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dabigatran etexilate; Drug: Dabigatran etexilate plus dronedarone; Drug: Dabigatran etexilate plus dronedarone; Drug: Dabigatran etexilate plus dronedarone; Drug: Dabigatran etexilate plus dronedarone

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Ulm, Germany
    • 1160.112.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Healthy male and female subjects

Exclusion criteria:

1. Any relevant deviation from healthy conditions

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A: Dabigatran alone (Reference); Capsule, oral administration with 240 mL water	Drug: Dabigatran etexilate; 150 mg as single dose
Experimental: B: Dabigatran plus Dronedarone (Test); Capsule and Tablets, oral administration with 240 mL water	Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose; Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose (staggered administration); Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid; Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid (staggered administration)
Experimental: C: Dabigatran plus Dronedarone (Test); Capsule and Tablets, oral administration with 240 mL water	Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose; Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose (staggered administration); Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid; Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid (staggered administration)
Experimental: D: Dabigatran plus Dronedarone (Test); Capsule and Tablets, oral administration with 240 mL water	Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose; Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose (staggered administration); Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid; Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid (staggered administration)
Experimental: E: Dabigatran plus Dronedarone (Test); Capsule and Tablets, oral administration with 240 mL water	Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose; Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose (staggered administration); Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid; Drug: Dabigatran etexilate plus dronedarone; dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid (staggered administration)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: February 28, 2011
• First Submitted That Met QC Criteria: February 28, 2011
• First Posted (Estimate): March 1, 2011

Study Record Updates

• Last Update Posted (Estimate): June 6, 2014
• Last Update Submitted That Met QC Criteria: June 3, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran; Dronedarone
• Other Study ID Numbers: 1160.112; 2010-024009-11 (EudraCT Number: EudraCT)