Trial Outcomes & Findings for Drug Interaction Study With Dabigatran Etexilate and Dronedarone in Healthy Subjects (NCT NCT01306162)
NCT ID: NCT01306162
Last Updated: 2014-06-06
Results Overview
Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
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
Results posted on
2014-06-06
Participant Flow
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.
Participant milestones
| Measure |
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)
|
|---|---|---|---|---|
|
Period 1
STARTED
|
9
|
9
|
9
|
9
|
|
Period 1
COMPLETED
|
9
|
9
|
9
|
8
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
1
|
|
Washout 1
STARTED
|
9
|
9
|
9
|
8
|
|
Washout 1
COMPLETED
|
9
|
8
|
9
|
8
|
|
Washout 1
NOT COMPLETED
|
0
|
1
|
0
|
0
|
|
Period 2
STARTED
|
9
|
8
|
9
|
8
|
|
Period 2
COMPLETED
|
9
|
8
|
9
|
8
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
9
|
8
|
9
|
8
|
|
Period 3
COMPLETED
|
9
|
8
|
9
|
8
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Washout 2
STARTED
|
9
|
8
|
9
|
8
|
|
Washout 2
COMPLETED
|
9
|
8
|
9
|
8
|
|
Washout 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
9
|
8
|
9
|
8
|
|
Period 4
COMPLETED
|
9
|
8
|
9
|
8
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
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)
|
|---|---|---|---|---|
|
Period 1
Adverse Event
|
0
|
0
|
0
|
1
|
|
Washout 1
Non-compliance to protocol
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Drug Interaction Study With Dabigatran Etexilate and Dronedarone in Healthy Subjects
Baseline characteristics by cohort
| Measure |
TrtA -- TrtB -- TrtD -- TrtE
n=9 Participants
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
n=9 Participants
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
n=9 Participants
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
n=9 Participants
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
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
32.2 Years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
37.8 Years
STANDARD_DEVIATION 10.4 • n=7 Participants
|
38.1 Years
STANDARD_DEVIATION 9.7 • n=5 Participants
|
33.3 Years
STANDARD_DEVIATION 7.9 • n=4 Participants
|
35.4 Years
STANDARD_DEVIATION 9.6 • n=21 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
17 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: Pharmacokinetic (PK) set defined as all subjects randomised, treated and who provided evaluable data for at least one observation for at least one primary endpoint without important protocol violations relevant to the evaluation of PK.
Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity.
Outcome measures
| Measure |
150mg DE (TrtA)
n=35 Participants
Dabigatran 150mg
|
150mg DE + 400mg DR (TrtB)
n=18 Participants
Dabigatran 150mg + Dronedarone 400mg given simultaneously
|
150mg DE + 400mg DR 2h Later (TrtC)
n=17 Participants
Dabigatran 150mg + Dronedarone 400mg given 2h later
|
150mg DE + 400mg DR Bid Same Time (TrtD)
n=34 Participants
Dabigatran 150mg + Dronedarone 400mg bid given simultaneously
|
150mg DE + 400mg DR Bid 2h Later (TrtE)
n=30 Participants
Dabigatran 150mg + Dronedarone 400mg bid given 2h later
|
|---|---|---|---|---|---|
|
Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)
|
1160 ng*hr/mL
Geometric Coefficient of Variation 40.3
|
2520 ng*hr/mL
Geometric Coefficient of Variation 27.1
|
1440 ng*hr/mL
Geometric Coefficient of Variation 40.3
|
2570 ng*hr/mL
Geometric Coefficient of Variation 28.1
|
1510 ng*hr/mL
Geometric Coefficient of Variation 32.9
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: PK set.
Maximum measured concentration of total dabigatran in plasma, per period.
Outcome measures
| Measure |
150mg DE (TrtA)
n=35 Participants
Dabigatran 150mg
|
150mg DE + 400mg DR (TrtB)
n=18 Participants
Dabigatran 150mg + Dronedarone 400mg given simultaneously
|
150mg DE + 400mg DR 2h Later (TrtC)
n=17 Participants
Dabigatran 150mg + Dronedarone 400mg given 2h later
|
150mg DE + 400mg DR Bid Same Time (TrtD)
n=34 Participants
Dabigatran 150mg + Dronedarone 400mg bid given simultaneously
|
150mg DE + 400mg DR Bid 2h Later (TrtE)
n=30 Participants
Dabigatran 150mg + Dronedarone 400mg bid given 2h later
|
|---|---|---|---|---|---|
|
Total Dabigatran: Maximum Measured Concentration (Cmax)
|
149 ng/mL
Geometric Coefficient of Variation 46.0
|
282 ng/mL
Geometric Coefficient of Variation 30.1
|
166 ng/mL
Geometric Coefficient of Variation 37.5
|
288 ng/mL
Geometric Coefficient of Variation 29.9
|
163 ng/mL
Geometric Coefficient of Variation 30.9
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PK set.
Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity.
Outcome measures
| Measure |
150mg DE (TrtA)
n=35 Participants
Dabigatran 150mg
|
150mg DE + 400mg DR (TrtB)
n=18 Participants
Dabigatran 150mg + Dronedarone 400mg given simultaneously
|
150mg DE + 400mg DR 2h Later (TrtC)
n=17 Participants
Dabigatran 150mg + Dronedarone 400mg given 2h later
|
150mg DE + 400mg DR Bid Same Time (TrtD)
n=34 Participants
Dabigatran 150mg + Dronedarone 400mg bid given simultaneously
|
150mg DE + 400mg DR Bid 2h Later (TrtE)
n=30 Participants
Dabigatran 150mg + Dronedarone 400mg bid given 2h later
|
|---|---|---|---|---|---|
|
Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)
|
919 ng*hr/mL
Geometric Coefficient of Variation 47.5
|
2110 ng*hr/mL
Geometric Coefficient of Variation 27.4
|
1110 ng*hr/mL
Geometric Coefficient of Variation 47.2
|
2100 ng*hr/mL
Geometric Coefficient of Variation 30.5
|
1260 ng*hr/mL
Geometric Coefficient of Variation 36.0
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PK set.
Maximum measured concentration of free dabigatran in plasma, per period.
Outcome measures
| Measure |
150mg DE (TrtA)
n=35 Participants
Dabigatran 150mg
|
150mg DE + 400mg DR (TrtB)
n=18 Participants
Dabigatran 150mg + Dronedarone 400mg given simultaneously
|
150mg DE + 400mg DR 2h Later (TrtC)
n=17 Participants
Dabigatran 150mg + Dronedarone 400mg given 2h later
|
150mg DE + 400mg DR Bid Same Time (TrtD)
n=34 Participants
Dabigatran 150mg + Dronedarone 400mg bid given simultaneously
|
150mg DE + 400mg DR Bid 2h Later (TrtE)
n=30 Participants
Dabigatran 150mg + Dronedarone 400mg bid given 2h later
|
|---|---|---|---|---|---|
|
Free Dabigatran: Maximum Measured Concentration (Cmax)
|
126 ng/mL
Geometric Coefficient of Variation 48.0
|
239 ng/mL
Geometric Coefficient of Variation 27.6
|
133 ng/mL
Geometric Coefficient of Variation 40.7
|
241 ng/mL
Geometric Coefficient of Variation 29.5
|
138 ng/mL
Geometric Coefficient of Variation 34.0
|
Adverse Events
150mg DE (TrtA)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
150mg DE + 400mg DR (TrtB)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
150mg DE + 400mg DR 2h Later (TrtC)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
150mg DE + 400mg DR Bid Same Time (TrtD)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
150mg DE + 400mg DR Bid 2h Later (TrtE)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
400mg DR + 400mg DR Bid 2h Later (TrtE2)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
150mg DE (TrtA)
n=35 participants at risk
Dabigatran 150mg
|
150mg DE + 400mg DR (TrtB)
n=18 participants at risk
Dabigatran 150mg + Dronedarone 400mg given simultaneously
|
150mg DE + 400mg DR 2h Later (TrtC)
n=17 participants at risk
Dabigatran 150mg + Dronedarone 400mg given 2h later
|
150mg DE + 400mg DR Bid Same Time (TrtD)
n=34 participants at risk
Dabigatran 150mg + Dronedarone 400mg bid given simultaneously
|
150mg DE + 400mg DR Bid 2h Later (TrtE)
n=30 participants at risk
Dabigatran 150mg + Dronedarone 400mg bid given 2h later
|
400mg DR + 400mg DR Bid 2h Later (TrtE2)
n=4 participants at risk
Dronedarone 400mg + Dronedarone 400mg bid given 2h later
|
|---|---|---|---|---|---|---|
|
Psychiatric disorders
Listless
|
0.00%
0/35 • 14 days
|
5.6%
1/18 • 14 days
|
0.00%
0/17 • 14 days
|
0.00%
0/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Nervous system disorders
Headache
|
8.6%
3/35 • 14 days
|
22.2%
4/18 • 14 days
|
5.9%
1/17 • 14 days
|
5.9%
2/34 • 14 days
|
6.7%
2/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Cardiac disorders
Atrioventricular block first degree
|
0.00%
0/35 • 14 days
|
0.00%
0/18 • 14 days
|
5.9%
1/17 • 14 days
|
0.00%
0/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Cardiac disorders
Palpitations
|
0.00%
0/35 • 14 days
|
0.00%
0/18 • 14 days
|
5.9%
1/17 • 14 days
|
0.00%
0/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/35 • 14 days
|
0.00%
0/18 • 14 days
|
5.9%
1/17 • 14 days
|
2.9%
1/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/35 • 14 days
|
0.00%
0/18 • 14 days
|
5.9%
1/17 • 14 days
|
0.00%
0/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/35 • 14 days
|
0.00%
0/18 • 14 days
|
5.9%
1/17 • 14 days
|
0.00%
0/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/35 • 14 days
|
5.6%
1/18 • 14 days
|
5.9%
1/17 • 14 days
|
0.00%
0/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Gastrointestinal disorders
Gastric disorder
|
0.00%
0/35 • 14 days
|
5.6%
1/18 • 14 days
|
5.9%
1/17 • 14 days
|
0.00%
0/34 • 14 days
|
3.3%
1/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/35 • 14 days
|
0.00%
0/18 • 14 days
|
5.9%
1/17 • 14 days
|
0.00%
0/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/35 • 14 days
|
0.00%
0/18 • 14 days
|
5.9%
1/17 • 14 days
|
0.00%
0/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
Reproductive system and breast disorders
Menstruation irregular
|
0.00%
0/35 • 14 days
|
0.00%
0/18 • 14 days
|
5.9%
1/17 • 14 days
|
0.00%
0/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
|
General disorders
Fatigue
|
0.00%
0/35 • 14 days
|
0.00%
0/18 • 14 days
|
5.9%
1/17 • 14 days
|
5.9%
2/34 • 14 days
|
0.00%
0/30 • 14 days
|
0.00%
0/4 • 14 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER