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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-024009-11 | EudraCT Number | EudraCT |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A: Dabigatran alone (Reference) | Experimental | Capsule, oral administration with 240 mL water |
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| B: Dabigatran plus Dronedarone (Test) | Experimental | Capsule and Tablets, oral administration with 240 mL water |
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| C: Dabigatran plus Dronedarone (Test) | Experimental | Capsule and Tablets, oral administration with 240 mL water |
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| D: Dabigatran plus Dronedarone (Test) | Experimental | Capsule and Tablets, oral administration with 240 mL water |
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| E: Dabigatran plus Dronedarone (Test) | Experimental | Capsule and Tablets, oral administration with 240 mL water |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dabigatran etexilate plus dronedarone | Drug | dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose |
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| 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 |
| 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 |
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Inclusion criteria:
1. Healthy male and female subjects
Exclusion criteria:
1. Any relevant deviation from healthy conditions
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1160.112.1 Boehringer Ingelheim Investigational Site | Ulm | Germany |
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Dabigatran etexilate | Drug | 150 mg as single dose |
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| Dabigatran etexilate plus dronedarone | Drug | dabigatran etexilate 150 mg plus dronedarone 400 mg as single dose (staggered administration) |
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| Dabigatran etexilate plus dronedarone | Drug | dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid |
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| Dabigatran etexilate plus dronedarone | Drug | dabigatran etexilate 150 mg single dose plus dronedarone 400 mg bid (staggered administration) |
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| 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 |
| 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) |
| FG002 | 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) |
| FG003 | 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) |
| COMPLETED |
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| NOT COMPLETED |
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| Washout 1 |
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| Period 2 |
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| Period 3 |
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| Washout 2 |
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| Period 4 |
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Treated set contains of all subjects who were dispensed study medication and were documented to have taken at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| BG001 | 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) |
| BG002 | 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) |
| BG003 | 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) |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| Primary | Total Dabigatran: Maximum Measured Concentration (Cmax) | Maximum measured concentration of total dabigatran in plasma, per period. | PK set. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
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| 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. | PK set. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| Secondary | Free Dabigatran: Maximum Measured Concentration (Cmax) | Maximum measured concentration of free dabigatran in plasma, per period. | PK set. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
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14 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 150mg DE (TrtA) | Dabigatran 150mg | 0 | 35 | 3 | 35 | ||
| EG001 | 150mg DE + 400mg DR (TrtB) | Dabigatran 150mg + Dronedarone 400mg given simultaneously | 0 | 18 | 6 | 18 | ||
| EG002 | 150mg DE + 400mg DR 2h Later (TrtC) | Dabigatran 150mg + Dronedarone 400mg given 2h later | 0 | 17 | 5 | 17 | ||
| EG003 | 150mg DE + 400mg DR Bid Same Time (TrtD) | Dabigatran 150mg + Dronedarone 400mg bid given simultaneously | 0 | 34 | 5 | 34 | ||
| EG004 | 150mg DE + 400mg DR Bid 2h Later (TrtE) | Dabigatran 150mg + Dronedarone 400mg bid given 2h later | 0 | 30 | 3 | 30 | ||
| EG005 | 400mg DR + 400mg DR Bid 2h Later (TrtE2) | Dronedarone 400mg + Dronedarone 400mg bid given 2h later | 0 | 4 | 0 | 4 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Listless | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Atrioventricular block first degree | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 14.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Gastric disorder | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
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| Menorrhagia | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
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| Menstruation irregular | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D000069604 | Dabigatran |
| D000077764 | Dronedarone |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D000638 | Amiodarone |
| D001572 | Benzofurans |
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| Male |
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Bioavailability |
| 150mg DE + 400mg DR 2h later (TrtC) vs 150mg DE (TrtA) | ANOVA | ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect. | 0.6697 | p-value for geometric mean ratio being outside interval 80% to 125% | Geometric mean ratio TrtC: TrtA (%) | 130 | Standard Deviation | 25.0 | 2-Sided | 90 | 112 | 151 | The standard deviation is actually the Geometric coefficient of variation | Yes | Non-Inferiority or Equivalence | Bioavailability |
| 150mg DE + 400mg DR bid same time (TrtD) vs 150mg DE (TrtA) | ANOVA | ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect. | 0.9992 | p-value for geometric mean ratio being outside interval 80% to 125% | Geometric mean ratio TrtD: TrtA (%) | 236 | Standard Deviation | 21.8 | 90 | 173 | 321 | The standard deviation is actually the Geometric coefficient of variation | Yes | Non-Inferiority or Equivalence | Bioavailability |
| 150mg DE + 400mg DR bid 2h later (TrtE) vs 150mg DE (TrtA) | ANOVA | ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect. | 0.9171 | p-value for geometric mean ratio being outside interval 80% to 125% | Geometric mean ratio TrtE: TrtA (%) | 162 | Standard Deviation | 20.1 | 2-Sided | 90 | 119 | 221 | The standard deviation is actually the Geometric coefficient of variation | Yes | Non-Inferiority or Equivalence | Bioavailability |
Dabigatran 150mg + Dronedarone 400mg bid given 2h later |
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Dabigatran 150mg + Dronedarone 400mg bid given 2h later |
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Dabigatran 150mg + Dronedarone 400mg bid given 2h later |
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