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Trial record 27 of 332 for:    DABIGATRAN

Bioequivalence of Two Different Capsule Types of Dabigatran

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ClinicalTrials.gov Identifier: NCT01290757
Recruitment Status : Completed
First Posted : February 7, 2011
Results First Posted : June 29, 2012
Last Update Posted : May 19, 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
Intervention Drug: Dabigatran etexilate
Enrollment 180
Recruitment Details  
Pre-assignment Details In this crossover study, subjects were randomly assigned to one of the 2 sequences, with 2 treatment arms. In general terms, Ref-Test-Ref-Test and Test-Ref-Test-Ref. The aim was bioequivalence comparing (Ref) Dabigatran 150mg in the currently approved capsule shell (Qualicaps) to the test of Dabigatran 150mg in a new shell (Capsugel).
Arm/Group Title Sequence: Qualicaps - Capsugel - Qualicaps - Capsugel Sequence: Capsugel - Qualicaps - Capsugel - Qualicaps
Hide Arm/Group Description Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel (RTRT) Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps (TRTR)
Period Title: Overall Study
Started 90 90
Completed 88 88
Not Completed 2 2
Reason Not Completed
Adverse Event             1             0
Protocol Violation             1             1
Other             0             1
Arm/Group Title Sequence: Qualicaps - Capsugel - Qualicaps - Capsugel Sequence: Capsugel - Qualicaps - Capsugel - Qualicaps Total
Hide Arm/Group Description Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel (RTRT) Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps (TRTR) Total of all reporting groups
Overall Number of Baseline Participants 90 90 180
Hide Baseline Analysis Population Description
Treated set includes all patients who received at least one study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 90 participants 90 participants 180 participants
39.8  (10.1) 39.4  (9.1) 39.6  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 90 participants 180 participants
Female
46
  51.1%
47
  52.2%
93
  51.7%
Male
44
  48.9%
43
  47.8%
87
  48.3%
1.Primary Outcome
Title Area Under the Curve 0 to tz (AUC0-tz) of Total Dabigatran
Hide Description Area under the concentration-time curve of total dabigatran in plasma from time 0 to the time of the last quantifiable data point, adjusted for treatment, period and sequence (all fixed effects), and random subject effect.
Time Frame 60 hours
Hide Outcome Measure Data
Hide Analysis Population Description
This subject set, the pharmacokinetic set (PKS), includes all subjects of the treated set who provide at least one evaluable observation for at least one of the three PK endpoints of total dabigatran, which is obtained in a period without important protocol violations relevant to the evaluation of bioequivalence.
Arm/Group Title Capsugel Qualicaps
Hide Arm/Group Description:
Dabigatran 150mg in new Capsugel
Dabigatran 150mg in currently approved Qualicaps
Overall Number of Participants Analyzed 179 180
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
1147.64
(32.32%)
908.48
(49.83%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capsugel, Qualicaps
Comments Capsugel minus Qualicaps
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence (BE). Scaled average BE is rejected, if the calculated upper 95% confidence limit of the linearized criterion is positive.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Upper 95% CI of the linearized criterion
Estimated Value -0.082
Estimation Comments Linearized regulatory criterion according to Tothfalusi et al (Pharmaceutical Research, 2001). The square of the difference in treatment responses divided by within-subject variance of the reference formulation minus square of ln(1.25)/0.25
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Capsugel, Qualicaps
Comments Capsugel vs Qualicaps
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence (BE). Bioequivalence is accepted if 90% confidence interval lies within the common BE margins (80% and 125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 126.33
Confidence Interval 90%
119.45 to 133.60
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum Measured Concentration (Cmax) of Total Dabigatran in Plasma
Hide Description Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.
Time Frame 60 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Capsugel Qualicaps
Hide Arm/Group Description:
Dabigatran 150mg in new Capsugel
Dabigatran 150mg in currently approved Qualicaps
Overall Number of Participants Analyzed 179 180
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
134.44
(31.10%)
107.13
(49.67%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capsugel, Qualicaps
Comments Capsugel minus Qualicaps
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence (BE). Scaled average BE is rejected, if the calculated upper 95% confidence limit of the linearized criterion is positive.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Upper 95% CI of the linearized criterion
Estimated Value -0.085
Estimation Comments Linearized regulatory criterion according to Tothfalusi et al (Pharmaceutical Research, 2001). The square of the difference in treatment responses divided by within-subject variance of the reference formulation minus square of ln(1.25)/0.25
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Capsugel, Qualicaps
Comments Capsugel vs Qualicaps
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence (BE). Bioequivalence is accepted if 90% confidence interval lies within the common BE margins (80% and 125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 125.49
Confidence Interval 90%
118.69 to 132.67
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Area Under the Curve 0 to Infinity (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. Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.
Time Frame 60 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Capsugel Qualicaps
Hide Arm/Group Description:
Dabigatran 150mg in new Capsugel
Dabigatran 150mg in currently approved Qualicaps
Overall Number of Participants Analyzed 179 180
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
1175.05
(30.81%)
941.99
(46.53%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capsugel, Qualicaps
Comments Capsugel vs Qualicaps
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence (BE). Bioequivalence is accepted if 90% confidence interval lies within the common BE margins (80% and 125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 124.74
Confidence Interval 90%
118.32 to 131.51
Estimation Comments [Not Specified]
4.Secondary Outcome
Title AUC0-tz of Free Dabigatran.
Hide Description Area under the concentration-time curve of free dabigatran in plasma from time 0 to the time of the last quantifiable data point. Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.
Time Frame 60 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Capsugel Qualicaps
Hide Arm/Group Description:
Dabigatran 150mg in new Capsugel
Dabigatran 150mg in currently approved Qualicaps
Overall Number of Participants Analyzed 179 180
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
856.31
(33.15%)
678.43
(50.85%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capsugel, Qualicaps
Comments Capsugel vs Qualicaps
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence (BE). Bioequivalence is accepted if 90% confidence interval lies within the common BE margins (80% and 125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 126.22
Confidence Interval 90%
119.36 to 133.47
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Cmax of Free Dabigatran in Plasma.
Hide Description Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.
Time Frame 60 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Capsugel Qualicaps
Hide Arm/Group Description:
Dabigatran 150mg in new Capsugel
Dabigatran 150mg in currently approved Qualicaps
Overall Number of Participants Analyzed 179 180
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
106.66
(31.34%)
85.12
(50.33%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capsugel, Qualicaps
Comments Capsugel vs Qualicaps
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence (BE). Bioequivalence is accepted if 90% confidence interval lies within the common BE margins (80% and 125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 125.30
Confidence Interval 90%
118.42 to 132.59
Estimation Comments [Not Specified]
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. Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.
Time Frame 60 hours
Hide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Capsugel Qualicaps
Hide Arm/Group Description:
Dabigatran 150mg in new Capsugel
Dabigatran 150mg in currently approved Qualicaps
Overall Number of Participants Analyzed 179 180
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
888.86
(31.20%)
714.01
(47.16%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capsugel, Qualicaps
Comments Capsugel vs Qualicaps
Type of Statistical Test Non-Inferiority or Equivalence
Comments Bioequivalence (BE). Bioequivalence is accepted if 90% confidence interval lies within the common BE margins (80% and 125%).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted geometric mean ratio (%)
Estimated Value 124.49
Confidence Interval 90%
118.11 to 131.21
Estimation Comments [Not Specified]
Time Frame Approximately 7 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Qualicaps Capsugel
Hide Arm/Group Description Dabigatran 150mg in Qualicaps Dabigatran 150mg in Capsugel
All-Cause Mortality
Qualicaps Capsugel
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Qualicaps Capsugel
Affected / at Risk (%) Affected / at Risk (%)
Total   0/180 (0.00%)   0/180 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Qualicaps Capsugel
Affected / at Risk (%) Affected / at Risk (%)
Total   37/180 (20.56%)   34/180 (18.89%) 
Nervous system disorders     
Headache  1  37/180 (20.56%)  34/180 (18.89%) 
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: NCT01290757     History of Changes
Other Study ID Numbers: 1160.117
2010-022966-28 ( EudraCT Number: EudraCT )
First Submitted: February 2, 2011
First Posted: February 7, 2011
Results First Submitted: April 18, 2012
Results First Posted: June 29, 2012
Last Update Posted: May 19, 2014