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Drug Interaction Study With Dabigatran Etexilate and Dronedarone in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT01306162
Recruitment Status : Completed
First Posted : March 1, 2011
Results First Posted : August 14, 2012
Last Update Posted : June 6, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: Dabigatran etexilate plus dronedarone
Drug: Dabigatran etexilate
Enrollment 36
Recruitment Details  
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.
Arm/Group Title TrtA -- TrtB -- TrtD -- TrtE TrtA -- TrtC -- TrtE -- TrtD TrtB -- TrtD -- TrtE -- TrtA TrtC -- TrtE -- TrtD -- TrtA
Hide Arm/Group Description 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) 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) 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) 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 Title: Period 1
Started 9 9 9 9
Completed 9 9 9 8
Not Completed 0 0 0 1
Reason Not Completed
Adverse Event             0             0             0             1
Period Title: Washout 1
Started 9 [1] 9 [1] 9 [2] 8 [3]
Completed 9 8 9 8
Not Completed 0 1 0 0
Reason Not Completed
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 Title: Period 2
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 Title: Period 3
Started 9 8 9 8
Completed 9 8 9 8
Not Completed 0 0 0 0
Period Title: Washout 2
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 Title: Period 4
Started 9 8 9 8
Completed 9 8 9 8
Not Completed 0 0 0 0
Arm/Group Title TrtA -- TrtB -- TrtD -- TrtE TrtA -- TrtC -- TrtE -- TrtD TrtB -- TrtD -- TrtE -- TrtA TrtC -- TrtE -- TrtD -- TrtA Total
Hide Arm/Group Description 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) 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) 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) 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 of all reporting groups
Overall Number of Baseline Participants 9 9 9 9 36
Hide Baseline Analysis Population Description
Treated set contains of all subjects who were dispensed study medication and were documented to have taken at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 9 participants 9 participants 9 participants 36 participants
32.2  (10.7) 37.8  (10.4) 38.1  (9.7) 33.3  (7.9) 35.4  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 9 participants 9 participants 9 participants 36 participants
Female
7
  77.8%
5
  55.6%
2
  22.2%
5
  55.6%
19
  52.8%
Male
2
  22.2%
4
  44.4%
7
  77.8%
4
  44.4%
17
  47.2%
1.Primary Outcome
Title Total Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 150mg DE (TrtA) 150mg DE + 400mg DR (TrtB) 150mg DE + 400mg DR 2h Later (TrtC) 150mg DE + 400mg DR Bid Same Time (TrtD) 150mg DE + 400mg DR Bid 2h Later (TrtE)
Hide Arm/Group Description:
Dabigatran 150mg
Dabigatran 150mg + Dronedarone 400mg given simultaneously
Dabigatran 150mg + Dronedarone 400mg given 2h later
Dabigatran 150mg + Dronedarone 400mg bid given simultaneously
Dabigatran 150mg + Dronedarone 400mg bid given 2h later
Overall Number of Participants Analyzed 35 18 17 34 30
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
1160
(40.3%)
2520
(27.1%)
1440
(40.3%)
2570
(28.1%)
1510
(32.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR (TrtB)
Comments 150mg DE + 400mg DR same time (TrtB) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 1.0000
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtB: TrtA (%)
Estimated Value 214
Confidence Interval (2-Sided) 90%
191 to 240
Parameter Dispersion
Type: Standard Deviation
Value: 19.9
Estimation Comments The standard deviation is actually the Geometric coefficient of variation.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR 2h Later (TrtC)
Comments 150mg DE + 400mg DR 2h later (TrtC) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.6697
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtC: TrtA (%)
Estimated Value 130
Confidence Interval (2-Sided) 90%
112 to 151
Parameter Dispersion
Type: Standard Deviation
Value: 25.0
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR Bid Same Time (TrtD)
Comments 150mg DE + 400mg DR bid same time (TrtD) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.9992
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtD: TrtA (%)
Estimated Value 236
Confidence Interval 90%
173 to 321
Parameter Dispersion
Type: Standard Deviation
Value: 21.8
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR Bid 2h Later (TrtE)
Comments 150mg DE + 400mg DR bid 2h later (TrtE) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.9171
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtE: TrtA (%)
Estimated Value 162
Confidence Interval (2-Sided) 90%
119 to 221
Parameter Dispersion
Type: Standard Deviation
Value: 20.1
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
2.Primary Outcome
Title Total Dabigatran: Maximum Measured Concentration (Cmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK set.
Arm/Group Title 150mg DE (TrtA) 150mg DE + 400mg DR (TrtB) 150mg DE + 400mg DR 2h Later (TrtC) 150mg DE + 400mg DR Bid Same Time (TrtD) 150mg DE + 400mg DR Bid 2h Later (TrtE)
Hide Arm/Group Description:
Dabigatran 150mg
Dabigatran 150mg + Dronedarone 400mg given simultaneously
Dabigatran 150mg + Dronedarone 400mg given 2h later
Dabigatran 150mg + Dronedarone 400mg bid given simultaneously
Dabigatran 150mg + Dronedarone 400mg bid given 2h later
Overall Number of Participants Analyzed 35 18 17 34 30
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
149
(46.0%)
282
(30.1%)
166
(37.5%)
288
(29.9%)
163
(30.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR (TrtB)
Comments 150mg DE + 400mg DR (TrtB) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.9999
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtB: TrtA (%)
Estimated Value 187
Confidence Interval (2-Sided) 90%
162 to 215
Parameter Dispersion
Type: Standard Deviation
Value: 24.3
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR 2h Later (TrtC)
Comments 150mg DE + 400mg DR 2h later (TrtC) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.2207
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtC: TrtA (%)
Estimated Value 115
Confidence Interval (2-Sided) 90%
95 to 138
Parameter Dispersion
Type: Standard Deviation
Value: 31.2
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR Bid Same Time (TrtD)
Comments 150mg DE + 400mg DR bid same time (TrtD) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.9946
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtD: TrtA (%)
Estimated Value 225
Confidence Interval 90%
156 to 326
Parameter Dispersion
Type: Standard Deviation
Value: 26.1
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR Bid 2h Later (TrtE)
Comments 150mg DE + 400mg DR bid 2h later (TrtE) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.6221
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtE: TrtA (%)
Estimated Value 133
Confidence Interval (2-Sided) 90%
94 to 190
Parameter Dispersion
Type: Standard Deviation
Value: 23.0
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
3.Secondary Outcome
Title Free Dabigatran: Area Under the Curve 0 to Infinity (AUC0-∞)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK set.
Arm/Group Title 150mg DE (TrtA) 150mg DE + 400mg DR (TrtB) 150mg DE + 400mg DR 2h Later (TrtC) 150mg DE + 400mg DR Bid Same Time (TrtD) 150mg DE + 400mg DR Bid 2h Later (TrtE)
Hide Arm/Group Description:
Dabigatran 150mg
Dabigatran 150mg + Dronedarone 400mg given simultaneously
Dabigatran 150mg + Dronedarone 400mg given 2h later
Dabigatran 150mg + Dronedarone 400mg bid given simultaneously
Dabigatran 150mg + Dronedarone 400mg bid given 2h later
Overall Number of Participants Analyzed 35 18 17 34 30
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
919
(47.5%)
2110
(27.4%)
1110
(47.2%)
2100
(30.5%)
1260
(36.0%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR (TrtB)
Comments 150mg DE + 400mg DR (TrtB) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 1.0000
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtB: TrtA (%)
Estimated Value 214
Confidence Interval (2-Sided) 90%
190 to 241
Parameter Dispersion
Type: Standard Deviation
Value: 20.7
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR 2h Later (TrtC)
Comments 150mg DE + 400mg DR 2h later (TrtC) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.7223
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtC: TrtA (%)
Estimated Value 132
Confidence Interval (2-Sided) 90%
113 to 155
Parameter Dispersion
Type: Standard Deviation
Value: 26.3
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR Bid Same Time (TrtD)
Comments 150mg DE + 400mg DR bid same time (TrtD) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.9993
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtD: TrtA (%)
Estimated Value 258
Confidence Interval 90%
182 to 365
Parameter Dispersion
Type: Standard Deviation
Value: 24.6
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR Bid 2h Later (TrtE)
Comments 150mg DE + 400mg DR bid 2h later (TrtE) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.8875
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtE: TrtA (%)
Estimated Value 159
Confidence Interval (2-Sided) 90%
114 to 222
Parameter Dispersion
Type: Standard Deviation
Value: 21.5
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
4.Secondary Outcome
Title Free Dabigatran: Maximum Measured Concentration (Cmax)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK set.
Arm/Group Title 150mg DE (TrtA) 150mg DE + 400mg DR (TrtB) 150mg DE + 400mg DR 2h Later (TrtC) 150mg DE + 400mg DR Bid Same Time (TrtD) 150mg DE + 400mg DR Bid 2h Later (TrtE)
Hide Arm/Group Description:
Dabigatran 150mg
Dabigatran 150mg + Dronedarone 400mg given simultaneously
Dabigatran 150mg + Dronedarone 400mg given 2h later
Dabigatran 150mg + Dronedarone 400mg bid given simultaneously
Dabigatran 150mg + Dronedarone 400mg bid given 2h later
Overall Number of Participants Analyzed 35 18 17 34 30
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
126
(48.0%)
239
(27.6%)
133
(40.7%)
241
(29.5%)
138
(34.0%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR (TrtB)
Comments 150mg DE + 400mg DR (TrtB) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.9998
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtB: TrtA (%)
Estimated Value 180
Confidence Interval (2-Sided) 90%
156 to 207
Parameter Dispersion
Type: Standard Deviation
Value: 24.6
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR 2h Later (TrtC)
Comments 150mg DE + 400mg DR 2h later (TrtC) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.1866
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtC: TrtA (%)
Estimated Value 114
Confidence Interval (2-Sided) 90%
95 to 136
Parameter Dispersion
Type: Standard Deviation
Value: 29.4
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR Bid Same Time (TrtD)
Comments 150mg DE + 400mg DR bid same time (TrtD) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.9958
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtD: TrtA (%)
Estimated Value 234
Confidence Interval 90%
160 to 340
Parameter Dispersion
Type: Standard Deviation
Value: 26.7
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 150mg DE (TrtA), 150mg DE + 400mg DR Bid 2h Later (TrtE)
Comments 150mg DE + 400mg DR bid 2h later (TrtE) vs 150mg DE (TrtA)
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioavailability
Statistical Test of Hypothesis P-Value 0.5164
Comments p-value for geometric mean ratio being outside interval 80% to 125%
Method ANOVA
Comments ANOVA with sequence, period and treatment as fixed effects and subject within sequence as random effect.
Method of Estimation Estimation Parameter Geometric mean ratio TrtE: TrtA (%)
Estimated Value 126
Confidence Interval (2-Sided) 90%
89 to 179
Parameter Dispersion
Type: Standard Deviation
Value: 22.6
Estimation Comments The standard deviation is actually the Geometric coefficient of variation
Time Frame 14 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 150mg DE (TrtA) 150mg DE + 400mg DR (TrtB) 150mg DE + 400mg DR 2h Later (TrtC) 150mg DE + 400mg DR Bid Same Time (TrtD) 150mg DE + 400mg DR Bid 2h Later (TrtE) 400mg DR + 400mg DR Bid 2h Later (TrtE2)
Hide Arm/Group Description Dabigatran 150mg Dabigatran 150mg + Dronedarone 400mg given simultaneously Dabigatran 150mg + Dronedarone 400mg given 2h later Dabigatran 150mg + Dronedarone 400mg bid given simultaneously Dabigatran 150mg + Dronedarone 400mg bid given 2h later Dronedarone 400mg + Dronedarone 400mg bid given 2h later
All-Cause Mortality
150mg DE (TrtA) 150mg DE + 400mg DR (TrtB) 150mg DE + 400mg DR 2h Later (TrtC) 150mg DE + 400mg DR Bid Same Time (TrtD) 150mg DE + 400mg DR Bid 2h Later (TrtE) 400mg DR + 400mg DR Bid 2h Later (TrtE2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
150mg DE (TrtA) 150mg DE + 400mg DR (TrtB) 150mg DE + 400mg DR 2h Later (TrtC) 150mg DE + 400mg DR Bid Same Time (TrtD) 150mg DE + 400mg DR Bid 2h Later (TrtE) 400mg DR + 400mg DR Bid 2h Later (TrtE2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/35 (0.00%)   0/18 (0.00%)   0/17 (0.00%)   0/34 (0.00%)   0/30 (0.00%)   0/4 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
150mg DE (TrtA) 150mg DE + 400mg DR (TrtB) 150mg DE + 400mg DR 2h Later (TrtC) 150mg DE + 400mg DR Bid Same Time (TrtD) 150mg DE + 400mg DR Bid 2h Later (TrtE) 400mg DR + 400mg DR Bid 2h Later (TrtE2)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/35 (8.57%)   6/18 (33.33%)   5/17 (29.41%)   5/34 (14.71%)   3/30 (10.00%)   0/4 (0.00%) 
Cardiac disorders             
Atrioventricular block first degree  1  0/35 (0.00%)  0/18 (0.00%)  1/17 (5.88%)  0/34 (0.00%)  0/30 (0.00%)  0/4 (0.00%) 
Palpitations  1  0/35 (0.00%)  0/18 (0.00%)  1/17 (5.88%)  0/34 (0.00%)  0/30 (0.00%)  0/4 (0.00%) 
Gastrointestinal disorders             
Gastric disorder  1  0/35 (0.00%)  1/18 (5.56%)  1/17 (5.88%)  0/34 (0.00%)  1/30 (3.33%)  0/4 (0.00%) 
General disorders             
Fatigue  1  0/35 (0.00%)  0/18 (0.00%)  1/17 (5.88%)  2/34 (5.88%)  0/30 (0.00%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/35 (0.00%)  0/18 (0.00%)  1/17 (5.88%)  0/34 (0.00%)  0/30 (0.00%)  0/4 (0.00%) 
Nervous system disorders             
Headache  1  3/35 (8.57%)  4/18 (22.22%)  1/17 (5.88%)  2/34 (5.88%)  2/30 (6.67%)  0/4 (0.00%) 
Psychiatric disorders             
Listless  1  0/35 (0.00%)  1/18 (5.56%)  0/17 (0.00%)  0/34 (0.00%)  0/30 (0.00%)  0/4 (0.00%) 
Reproductive system and breast disorders             
Menorrhagia  1  0/35 (0.00%)  0/18 (0.00%)  1/17 (5.88%)  0/34 (0.00%)  0/30 (0.00%)  0/4 (0.00%) 
Menstruation irregular  1  0/35 (0.00%)  0/18 (0.00%)  1/17 (5.88%)  0/34 (0.00%)  0/30 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Cough  1  0/35 (0.00%)  0/18 (0.00%)  1/17 (5.88%)  1/34 (2.94%)  0/30 (0.00%)  0/4 (0.00%) 
Dysphonia  1  0/35 (0.00%)  0/18 (0.00%)  1/17 (5.88%)  0/34 (0.00%)  0/30 (0.00%)  0/4 (0.00%) 
Dyspnoea  1  0/35 (0.00%)  0/18 (0.00%)  1/17 (5.88%)  0/34 (0.00%)  0/30 (0.00%)  0/4 (0.00%) 
Oropharyngeal pain  1  0/35 (0.00%)  1/18 (5.56%)  1/17 (5.88%)  0/34 (0.00%)  0/30 (0.00%)  0/4 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01306162     History of Changes
Other Study ID Numbers: 1160.112
2010-024009-11 ( EudraCT Number: EudraCT )
First Submitted: February 28, 2011
First Posted: March 1, 2011
Results First Submitted: May 23, 2012
Results First Posted: August 14, 2012
Last Update Posted: June 6, 2014