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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)

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01306162
Enrollment
36
Registered
2011-03-01
Start date
2011-02-28
Completion date
Unknown
Last updated
2014-06-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

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

Interventions

DRUGDabigatran etexilate plus dronedarone

dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose

DRUGDabigatran etexilate

150 mg as single dose

Sponsors

Boehringer Ingelheim
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes

Inclusion criteria

1\. Healthy male and female subjects

Exclusion criteria

1\. Any relevant deviation from healthy conditions

Design outcomes

Primary

MeasureTime frameDescription
Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)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 administrationArea under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity.
Total Dabigatran: Maximum Measured Concentration (Cmax)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 administrationMaximum measured concentration of total dabigatran in plasma, per period.

Secondary

MeasureTime frameDescription
Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)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 administrationArea under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity.
Free Dabigatran: Maximum Measured Concentration (Cmax)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 administrationMaximum measured concentration of free dabigatran in plasma, per period.

Countries

Germany

Participant flow

Pre-assignment details

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.

Participants by arm

ArmCount
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)
9
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)
9
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)
9
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)
9
Total36

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Period 1Adverse Event0001
Washout 1Non-compliance to protocol0100

Baseline characteristics

CharacteristicTrtA -- TrtB -- TrtD -- TrtETrtA -- TrtC -- TrtE -- TrtDTrtB -- TrtD -- TrtE -- TrtATrtC -- TrtE -- TrtD -- TrtATotal
Age, Continuous32.2 Years
STANDARD_DEVIATION 10.7
37.8 Years
STANDARD_DEVIATION 10.4
38.1 Years
STANDARD_DEVIATION 9.7
33.3 Years
STANDARD_DEVIATION 7.9
35.4 Years
STANDARD_DEVIATION 9.6
Sex: Female, Male
Female
7 Participants5 Participants2 Participants5 Participants19 Participants
Sex: Female, Male
Male
2 Participants4 Participants7 Participants4 Participants17 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —— / —— / —
other
Total, other adverse events
3 / 356 / 185 / 175 / 343 / 300 / 4
serious
Total, serious adverse events
0 / 350 / 180 / 170 / 340 / 300 / 4

Outcome results

Primary

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.

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

Population: 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.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
150mg DE (TrtA)Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)1160 ng*hr/mLGeometric Coefficient of Variation 40.3
150mg DE + 400mg DR (TrtB)Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)2520 ng*hr/mLGeometric Coefficient of Variation 27.1
150mg DE + 400mg DR 2h Later (TrtC)Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)1440 ng*hr/mLGeometric Coefficient of Variation 40.3
150mg DE + 400mg DR Bid Same Time (TrtD)Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)2570 ng*hr/mLGeometric Coefficient of Variation 28.1
150mg DE + 400mg DR Bid 2h Later (TrtE)Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)1510 ng*hr/mLGeometric Coefficient of Variation 32.9
Comparison: 150mg DE + 400mg DR same time (TrtB) vs 150mg DE (TrtA)p-value: 190% CI: [191, 240]ANOVA
Comparison: 150mg DE + 400mg DR 2h later (TrtC) vs 150mg DE (TrtA)p-value: 0.669790% CI: [112, 151]ANOVA
Comparison: 150mg DE + 400mg DR bid same time (TrtD) vs 150mg DE (TrtA)p-value: 0.999290% CI: [173, 321]ANOVA
Comparison: 150mg DE + 400mg DR bid 2h later (TrtE) vs 150mg DE (TrtA)p-value: 0.917190% CI: [119, 221]ANOVA
Primary

Total Dabigatran: Maximum Measured Concentration (Cmax)

Maximum measured concentration of total dabigatran in plasma, per period.

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

Population: PK set.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
150mg DE (TrtA)Total Dabigatran: Maximum Measured Concentration (Cmax)149 ng/mLGeometric Coefficient of Variation 46
150mg DE + 400mg DR (TrtB)Total Dabigatran: Maximum Measured Concentration (Cmax)282 ng/mLGeometric Coefficient of Variation 30.1
150mg DE + 400mg DR 2h Later (TrtC)Total Dabigatran: Maximum Measured Concentration (Cmax)166 ng/mLGeometric Coefficient of Variation 37.5
150mg DE + 400mg DR Bid Same Time (TrtD)Total Dabigatran: Maximum Measured Concentration (Cmax)288 ng/mLGeometric Coefficient of Variation 29.9
150mg DE + 400mg DR Bid 2h Later (TrtE)Total Dabigatran: Maximum Measured Concentration (Cmax)163 ng/mLGeometric Coefficient of Variation 30.9
Comparison: 150mg DE + 400mg DR (TrtB) vs 150mg DE (TrtA)p-value: 0.999990% CI: [162, 215]ANOVA
Comparison: 150mg DE + 400mg DR 2h later (TrtC) vs 150mg DE (TrtA)p-value: 0.220790% CI: [95, 138]ANOVA
Comparison: 150mg DE + 400mg DR bid same time (TrtD) vs 150mg DE (TrtA)p-value: 0.994690% CI: [156, 326]ANOVA
Comparison: 150mg DE + 400mg DR bid 2h later (TrtE) vs 150mg DE (TrtA)p-value: 0.622190% CI: [94, 190]ANOVA
Secondary

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.

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

Population: PK set.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
150mg DE (TrtA)Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)919 ng*hr/mLGeometric Coefficient of Variation 47.5
150mg DE + 400mg DR (TrtB)Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)2110 ng*hr/mLGeometric Coefficient of Variation 27.4
150mg DE + 400mg DR 2h Later (TrtC)Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)1110 ng*hr/mLGeometric Coefficient of Variation 47.2
150mg DE + 400mg DR Bid Same Time (TrtD)Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)2100 ng*hr/mLGeometric Coefficient of Variation 30.5
150mg DE + 400mg DR Bid 2h Later (TrtE)Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)1260 ng*hr/mLGeometric Coefficient of Variation 36
Comparison: 150mg DE + 400mg DR (TrtB) vs 150mg DE (TrtA)p-value: 190% CI: [190, 241]ANOVA
Comparison: 150mg DE + 400mg DR 2h later (TrtC) vs 150mg DE (TrtA)p-value: 0.722390% CI: [113, 155]ANOVA
Comparison: 150mg DE + 400mg DR bid same time (TrtD) vs 150mg DE (TrtA)p-value: 0.999390% CI: [182, 365]ANOVA
Comparison: 150mg DE + 400mg DR bid 2h later (TrtE) vs 150mg DE (TrtA)p-value: 0.887590% CI: [114, 222]ANOVA
Secondary

Free Dabigatran: Maximum Measured Concentration (Cmax)

Maximum measured concentration of free dabigatran in plasma, per period.

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

Population: PK set.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
150mg DE (TrtA)Free Dabigatran: Maximum Measured Concentration (Cmax)126 ng/mLGeometric Coefficient of Variation 48
150mg DE + 400mg DR (TrtB)Free Dabigatran: Maximum Measured Concentration (Cmax)239 ng/mLGeometric Coefficient of Variation 27.6
150mg DE + 400mg DR 2h Later (TrtC)Free Dabigatran: Maximum Measured Concentration (Cmax)133 ng/mLGeometric Coefficient of Variation 40.7
150mg DE + 400mg DR Bid Same Time (TrtD)Free Dabigatran: Maximum Measured Concentration (Cmax)241 ng/mLGeometric Coefficient of Variation 29.5
150mg DE + 400mg DR Bid 2h Later (TrtE)Free Dabigatran: Maximum Measured Concentration (Cmax)138 ng/mLGeometric Coefficient of Variation 34
Comparison: 150mg DE + 400mg DR (TrtB) vs 150mg DE (TrtA)p-value: 0.999890% CI: [156, 207]ANOVA
Comparison: 150mg DE + 400mg DR 2h later (TrtC) vs 150mg DE (TrtA)p-value: 0.186690% CI: [95, 136]ANOVA
Comparison: 150mg DE + 400mg DR bid same time (TrtD) vs 150mg DE (TrtA)p-value: 0.995890% CI: [160, 340]ANOVA
Comparison: 150mg DE + 400mg DR bid 2h later (TrtE) vs 150mg DE (TrtA)p-value: 0.516490% CI: [89, 179]ANOVA

Source: ClinicalTrials.gov · Data processed: Mar 9, 2026