Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 333 for:    DABIGATRAN

Bioequivalence of Tablet Formulation of Dabigatran Etexilate Compared to Commercial Capsule Formulation Following Oral Administration in Healthy Male Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03070171
Recruitment Status : Completed
First Posted : March 3, 2017
Results First Posted : January 9, 2019
Last Update Posted : January 9, 2019
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
Intervention Drug: dabigatran etexilate
Enrollment 160
Recruitment Details Randomised, single-dose, open-label, replicate design in a two-treatments, four-period, two-sequence crossover design (T:Dabigatran etexilate tablet formulation 110 mg and R: Dabigatran etexilate capsule formulation 110 mg)
Pre-assignment Details All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they (the subjects) met all implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial drug if any of the specific entry criteria was violated.
Arm/Group Title T-R-R-T R-T-T-R
Hide Arm/Group Description Subjects were treated with single oral dose, started in period 1 with 110 milligram (mg) Dabigatran etexilate tablet with 200 milliliter (mL) of water after an overnight fast of at least 10 hour (h), followed in period 2 and period 3 by 110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h, and in period 4 by 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h. Treatment periods were separated by a wash-out phase of at least 4 days. Subjects were treated with single oral dose, started in period 1 with 110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h, followed in period 2 and period 3 by 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h, and in period 4 by 110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h. Treatment periods were separated by a wash-out phase of at least 4 days.
Period Title: Treatment Period 1 + Washout
Started 80 80
Completed 80 80
Not Completed 0 0
Period Title: Treatment Period 2 + Washout
Started 80 80
Completed 80 79
Not Completed 0 1
Reason Not Completed
Other Adverse Event             0             1
Period Title: Treatment Period 3 + Washout
Started 80 79
Completed 80 79
Not Completed 0 0
Period Title: Treatment Period 4 + Washout
Started 80 79
Completed 80 78
Not Completed 0 1
Reason Not Completed
Withdrawal by Subject             0             1
Arm/Group Title T-R-R-T R-T-T-R Total
Hide Arm/Group Description Subjects were treated with single oral dose, started in period 1 with 110 milligram (mg) Dabigatran etexilate tablet with 200 milliliter (mL) of water after an overnight fast of at least 10 hour (h), followed in period 2 and period 3 by 110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h, and in period 4 by 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h. Treatment periods were separated by a wash-out phase of at least 4 days. Subjects were treated with single oral dose, started in period 1 with 110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h, followed in period 2 and period 3 by 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h, and in period 4 by 110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h. Treatment periods were separated by a wash-out phase of at least 4 days. Total of all reporting groups
Overall Number of Baseline Participants 80 80 160
Hide Baseline Analysis Population Description
Treated set (TS): This subject set included all subjects from the Randomised Set (RS) who were dispensed study medication and were documented to have taken at least 1 dose of investigational treatment.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 80 participants 80 participants 160 participants
27.2  (4.2) 27.3  (4.2) 27.2  (4.2)
[1]
Measure Description: Age at the time of signing informed consent form is presented.
[2]
Measure Analysis Population Description: TS
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 80 participants 160 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
80
 100.0%
80
 100.0%
160
 100.0%
[1]
Measure Analysis Population Description: TS
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 80 participants 160 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
80
 100.0%
80
 100.0%
160
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: TS
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 80 participants 80 participants 160 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
80
 100.0%
80
 100.0%
160
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: TS
1.Primary Outcome
Title AUC0-tz of Free Dabigatran
Hide Description

Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz). Geometric Mean (gMean) is actually Adjusted gMean & Geometric Coefficient of Variation (gCV) is actually Intra individual gCV (%gCV).

PK exclusion criteria: 1) The subject experienced emesis at or before 2 times median Time from (last) dosing to the maximum measured concentration of the analyte in plasma (tmax). Median tmax was to be taken either from the median tmax for reference product or test product, depending on whether the subject had experienced emesis after taken the test or reference product. Median tmax was to be determined excluding the subjects experiencing emesis. 2) Time deviations 3) Use of restricted medications 4) A pre-dose concentration was >5% of the Cmax value of that subject.

Time Frame 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic set (PKS): All subjects from Treated Set (TS) who provided at least 1 observation for at least 1 primary endpoint that was not excluded as per PK exclusion criteria (defined in the description).
Arm/Group Title Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Hide Arm/Group Description:
Patients were administered single oral dose of 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h
Patients were administered single oral dose of110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h
Overall Number of Participants Analyzed 159 160
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram*hour/milliliter (ng・h/mL)
725.03686
(57.00406%)
668.42714
(52.33393%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate Tablet (T), Dabigatran Etexilate Capsule (R)
Comments The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for ‘sequence’, ‘subjects nested within sequences’, ‘period’ and ‘treatment’.
Type of Statistical Test Equivalence
Comments Bioequivalence was established by ensuring that the T/R ratio of AUC0-tz of free dabigatran was within the pre-specified acceptance range (80%-125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R Ratio
Estimated Value 108.46909
Confidence Interval (2-Sided) 90%
101.44605 to 115.97833
Estimation Comments Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
2.Primary Outcome
Title Cmax of Free Dabigatran
Hide Description Maximum plasma concentration of free dabigatran (Cmax). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.
Time Frame 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Hide Arm/Group Description:
Patients were administered single oral dose of 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h
Patients were administered single oral dose of110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h
Overall Number of Participants Analyzed 159 160
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram/milliliter (ng/mL)
86.26026
(56.43338%)
79.16785
(55.20456%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate Tablet (T), Dabigatran Etexilate Capsule (R)
Comments The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for ‘sequence’, ‘subjects nested within sequences’, ‘period’ and ‘treatment’.
Type of Statistical Test Equivalence
Comments Bioequivalence was established by ensuring that the T/R ratio of Cmax of free dabigatran was within the pre-specified acceptance range (80%-125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R Ratio
Estimated Value 108.9587
Confidence Interval (2-Sided) 90%
101.78627 to 116.63654
Estimation Comments Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
3.Secondary Outcome
Title AUC0-tz of Total Dabigatran
Hide Description

Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz ).

Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

Time Frame 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Hide Arm/Group Description:
Patients were administered single oral dose of 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h
Patients were administered single oral dose of110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h
Overall Number of Participants Analyzed 159 160
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng•h/mL
847.26720
(57.32236%)
787.31279
(52.53129%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate Tablet (T), Dabigatran Etexilate Capsule (R)
Comments The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for ‘sequence’, ‘subjects nested within sequences’, ‘period’ and ‘treatment’.
Type of Statistical Test Equivalence
Comments Bioequivalence was established by ensuring that the T/R ratio of Cmax of free dabigatran was within the pre-specified acceptance range (80%-125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R Ratio
Estimated Value 107.61507
Confidence Interval (2-Sided) 90%
100.61938 to 115.09714
Estimation Comments Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
4.Secondary Outcome
Title Cmax of Total Dabigatran
Hide Description Maximum plasma concentration of total dabigatran (Cmax). Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.
Time Frame 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Hide Arm/Group Description:
Patients were administered single oral dose of 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h
Patients were administered single oral dose of110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h
Overall Number of Participants Analyzed 159 160
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
99.81133
(58.31846%)
93.54769
(56.54651%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate Tablet (T), Dabigatran Etexilate Capsule (R)
Comments The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for ‘sequence’, ‘subjects nested within sequences’, ‘period’ and ‘treatment’.
Type of Statistical Test Equivalence
Comments Bioequivalence was established by ensuring that the T/R ratio of Cmax of total dabigatran was within the pre-specified acceptance range (80%-125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R Ratio
Estimated Value 106.69566
Confidence Interval (2-Sided) 90%
99.50139 to 114.41010
Estimation Comments Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
5.Secondary Outcome
Title AUC0-∞ of Total Dabigatran
Hide Description

Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).

Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

Time Frame 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Hide Arm/Group Description:
Patients were administered single oral dose of 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h
Patients were administered single oral dose of110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h
Overall Number of Participants Analyzed 159 160
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng•h/mL
877.70198
(52.04260%)
813.94379
(49.99079%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate Tablet (T), Dabigatran Etexilate Capsule (R)
Comments The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for ‘sequence’, ‘subjects nested within sequences’, ‘period’ and ‘treatment’.
Type of Statistical Test Equivalence
Comments Bioequivalence was established by ensuring that the T/R ratio of AUC0-∞ of total dabigatran was within the pre-specified acceptance range (80%-125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R Ratio
Estimated Value 107.83324
Confidence Interval (2-Sided) 90%
101.25584 to 114.83790
Estimation Comments Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
6.Secondary Outcome
Title AUC0-∞ of Free Dabigatran
Hide Description

Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).

Geometric Mean is actually Adjusted geometric mean and Geometric Coefficient of Variation (gCV) is actually Intra individual gCV.

Time Frame 1:00h before drug administration and 0:30h, 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h and 48:00h after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Hide Arm/Group Description:
Patients were administered single oral dose of 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h
Patients were administered single oral dose of110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h
Overall Number of Participants Analyzed 159 160
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng•h/mL
753.13668
(51.62318%)
694.57320
(49.42941%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabigatran Etexilate Tablet (T), Dabigatran Etexilate Capsule (R)
Comments The statistical model was an analysis of variance (ANOVA) on the logarithmic scale including effects for ‘sequence’, ‘subjects nested within sequences’, ‘period’ and ‘treatment’.
Type of Statistical Test Equivalence
Comments Bioequivalence was established by ensuring that the T/R ratio of AUC0-∞ of free dabigatran was within the pre-specified acceptance range (80%-125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter T/R Ratio
Estimated Value 108.43158
Confidence Interval (2-Sided) 90%
101.87254 to 115.41292
Estimation Comments Confidence intervals were calculated based on the residual error from ANOVA. Ratio calculated as Dabigatran Etexilate Tablet (T) divided by Dabigatran Etexilate capsule (R).
Time Frame From first drug administration until 3 day after the last drug administration, ie upto 7 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Hide Arm/Group Description Patients were administered single oral dose of 110 mg Dabigatran etexilate tablet with 200 mL of water after an overnight fast of at least 10 h Patients were administered single oral dose of110 mg Dabigatran etexilate capsule with 200 mL of water after an overnight fast of at least 10 h
All-Cause Mortality
Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/159 (0.00%)   0/160 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/159 (0.00%)   0/160 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dabigatran Etexilate Tablet (T) Dabigatran Etexilate Capsule (R)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/159 (0.00%)   0/160 (0.00%) 
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.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03070171     History of Changes
Other Study ID Numbers: 1160-0271
First Submitted: February 28, 2017
First Posted: March 3, 2017
Results First Submitted: June 12, 2018
Results First Posted: January 9, 2019
Last Update Posted: January 9, 2019