Drug Interaction Study With Dabigatran Etexilate and Dronedarone in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01306162
First received: February 28, 2011
Last updated: June 3, 2014
Last verified: April 2014
Results First Received: May 23, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Healthy
Interventions: Drug: Dabigatran etexilate plus dronedarone
Drug: Dabigatran etexilate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In this crossover study, subjects were randomly assigned to one of the 4 sequences, but with 5 treatments. In general terms ABDE,ACED,BDEA,CEDA. There were four subjects in Trt E who took Dronedarone mistakenly in place of Dabigatran. These are presented separately for adverse events.

Reporting Groups
  Description
TrtA -- TrtB -- TrtD -- TrtE Dabigatran 150mg (Trt. A), followed by Dabigatran 150mg + Dronedarone 400mg given simultaneously (Trt. B), followed by Dabigatran 150mg + Dronedarone 400mg bid given simultaneously (Trt. D), followed by Dabigatran 150mg + Dronedarone 400mg bid given 2h later (Trt. E)
TrtA -- TrtC -- TrtE -- TrtD Dabigatran 150mg (Trt. A), followed by Dabigatran 150mg + Dronedarone 400mg given 2h later (Trt. C), followed by Dabigatran 150mg + Dronedarone 400mg bid given 2h later (Trt. E), followed by Dabigatran 150mg + Dronedarone 400mg bid given simultaneously (Trt. D)
TrtB -- TrtD -- TrtE -- TrtA Dabigatran 150mg + Dronedarone 400mg given simultaneously (Trt. B), followed by Dabigatran 150mg + Dronedarone 400mg bid given simultaneously (Trt. D), followed by Dabigatran 150mg + Dronedarone 400mg bid given 2h later (Trt. E), followed by Dabigatran 150mg (Trt. A)
TrtC -- TrtE -- TrtD -- TrtA Dabigatran 150mg + Dronedarone 400mg given 2h later (Trt. C), followed by Dabigatran 150mg + Dronedarone 400mg bid given 2h later (Trt. E), followed by Dabigatran 150mg + Dronedarone 400mg bid given simultaneously (Trt. D), followed by Dabigatran 150mg (Trt. A)

Participant Flow for 6 periods

Period 1:   Period 1
    TrtA -- TrtB -- TrtD -- TrtE     TrtA -- TrtC -- TrtE -- TrtD     TrtB -- TrtD -- TrtE -- TrtA     TrtC -- TrtE -- TrtD -- TrtA  
STARTED     9     9     9     9  
COMPLETED     9     9     9     8  
NOT COMPLETED     0     0     0     1  
Adverse Event                 0                 0                 0                 1  

Period 2:   Washout 1
    TrtA -- TrtB -- TrtD -- TrtE     TrtA -- TrtC -- TrtE -- TrtD     TrtB -- TrtD -- TrtE -- TrtA     TrtC -- TrtE -- TrtD -- TrtA  
STARTED     9 [1]   9 [1]   9 [2]   8 [3]
COMPLETED     9     8     9     8  
NOT COMPLETED     0     1     0     0  
Non-compliance to protocol                 0                 1                 0                 0  
[1] Treatment A was followed by a washout period of at least 96 hours.
[2] No washout period. Treatment D followed directly after treatment B.
[3] No washout period.Treatment E followed directly after treatment C.

Period 3:   Period 2
    TrtA -- TrtB -- TrtD -- TrtE     TrtA -- TrtC -- TrtE -- TrtD     TrtB -- TrtD -- TrtE -- TrtA     TrtC -- TrtE -- TrtD -- TrtA  
STARTED     9 [1]   8 [1]   9 [1]   8 [1]
COMPLETED     9     8     9     8  
NOT COMPLETED     0     0     0     0  
[1] No washout phase after Period 2.

Period 4:   Period 3
    TrtA -- TrtB -- TrtD -- TrtE     TrtA -- TrtC -- TrtE -- TrtD     TrtB -- TrtD -- TrtE -- TrtA     TrtC -- TrtE -- TrtD -- TrtA  
STARTED     9     8     9     8  
COMPLETED     9     8     9     8  
NOT COMPLETED     0     0     0     0  

Period 5:   Washout 2
    TrtA -- TrtB -- TrtD -- TrtE     TrtA -- TrtC -- TrtE -- TrtD     TrtB -- TrtD -- TrtE -- TrtA     TrtC -- TrtE -- TrtD -- TrtA  
STARTED     9 [1]   8 [2]   9 [3]   8 [3]
COMPLETED     9     8     9     8  
NOT COMPLETED     0     0     0     0  
[1] No washout period. Treatment E followed directly after treatment D.
[2] No washout period. Treatment D followed directly after treatment E.
[3] The last dose of Dronedarone was followed by a washout period of at least 10 days.

Period 6:   Period 4
    TrtA -- TrtB -- TrtD -- TrtE     TrtA -- TrtC -- TrtE -- TrtD     TrtB -- TrtD -- TrtE -- TrtA     TrtC -- TrtE -- TrtD -- TrtA  
STARTED     9     8     9     8  
COMPLETED     9     8     9     8  
NOT COMPLETED     0     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated set contains of all subjects who were dispensed study medication and were documented to have taken at least one dose of study drug.

Reporting Groups
  Description
TrtA -- TrtB -- TrtD -- TrtE Dabigatran 150mg (Trt. A), followed by Dabigatran 150mg + Dronedarone 400mg given simultaneously (Trt. B), followed by Dabigatran 150mg + Dronedarone 400mg bid given simultaneously (Trt. D), followed by Dabigatran 150mg + Dronedarone 400mg bid given 2h later (Trt. E)
TrtA -- TrtC -- TrtE -- TrtD Dabigatran 150mg (Trt. A), followed by Dabigatran 150mg + Dronedarone 400mg given 2h later (Trt. C), followed by Dabigatran 150mg + Dronedarone 400mg bid given 2h later (Trt. E), followed by Dabigatran 150mg + Dronedarone 400mg bid given simultaneously (Trt. D)
TrtB -- TrtD -- TrtE -- TrtA Dabigatran 150mg + Dronedarone 400mg given simultaneously (Trt. B), followed by Dabigatran 150mg + Dronedarone 400mg bid given simultaneously (Trt. D), followed by Dabigatran 150mg + Dronedarone 400mg bid given 2h later (Trt. E), followed by Dabigatran 150mg (Trt. A)
TrtC -- TrtE -- TrtD -- TrtA Dabigatran 150mg + Dronedarone 400mg given 2h later (Trt. C), followed by Dabigatran 150mg + Dronedarone 400mg bid given 2h later (Trt. E), followed by Dabigatran 150mg + Dronedarone 400mg bid given simultaneously (Trt. D), followed by Dabigatran 150mg (Trt. A)
Total Total of all reporting groups

Baseline Measures
    TrtA -- TrtB -- TrtD -- TrtE     TrtA -- TrtC -- TrtE -- TrtD     TrtB -- TrtD -- TrtE -- TrtA     TrtC -- TrtE -- TrtD -- TrtA     Total  
Number of Participants  
[units: participants]
  9     9     9     9     36  
Age  
[units: Years]
Mean ± Standard Deviation
  32.2  ± 10.7     37.8  ± 10.4     38.1  ± 9.7     33.3  ± 7.9     35.4  ± 9.6  
Gender  
[units: Participants]
         
Female     7     5     2     5     19  
Male     2     4     7     4     17  



  Outcome Measures
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1.  Primary:   Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)   [ Time Frame: 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 ]

2.  Primary:   Total Dabigatran: Maximum Measured Concentration (Cmax)   [ Time Frame: 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 ]

3.  Secondary:   Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)   [ Time Frame: 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 ]

4.  Secondary:   Free Dabigatran: Maximum Measured Concentration (Cmax)   [ Time Frame: 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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided


Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01306162     History of Changes
Other Study ID Numbers: 1160.112, 2010-024009-11
Study First Received: February 28, 2011
Results First Received: May 23, 2012
Last Updated: June 3, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices