Trial Outcomes & Findings for Bioavailability Study of Five Tablet Formulations of Dabigatran Etexilate Compared to Commercial Capsule Formulation in Healthy Male Subjects (NCT NCT02710630)

Last Updated: 2017-11-06

Results Overview

This outcome measure presents 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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.

Results posted on

2017-11-06

Participant Flow

Participant milestones

Participant milestones
Measure	Ref-A1-B1-C1-D1-E1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation A1 (TF-A1) in period 2, followed by Test Formulation B1 (TF-B1) in period 3, followed by Test Formulation C1 (TF-C1) in period 4, followed by Test Formulation D1 (TF-D1) in period 5, followed by Test Formulation E1 (TF-E1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.	Ref-B1-C1-D1-E1-A1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation B1 (TF-B1) in period 2, followed by Test Formulation C1 (TF-C1) in period 3, followed by Test Formulation D1 (TF-D1) in period 4, followed by Test Formulation E1 (TF-E1) in period 5, followed by Test Formulation A1 (TF-A1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.	Ref-C1-D1-E1-A1-B1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation C1 (TF-C1) in period 2, followed by Test Formulation D1 (TF-D1) in period 3, followed by Test Formulation E1 (TF-E1) in period 4, followed by Test Formulation A1 (TF-A1) in period 5, followed by Test Formulation B1 (TF-B1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.	Ref-D1-E1-A1-B1-C1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation D1 (TF-D1) in period 2, followed by Test Formulation E1 (TF-E1) in period 3, followed by Test Formulation A1 (TF-A1) in period 4, followed by Test Formulation B1 (TF-B1) in period 5, followed by Test Formulation C1 (TF-C1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.	Ref-E1-A1-B1-C1-D1 All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation E1 (TF-E1) in period 2, followed by Test Formulation A1 (TF-A1) in period 3, followed by Test Formulation B1 (TF-B1) in period 4, followed by Test Formulation C1 (TF-C1) in period 5, followed by Test Formulation D1 (TF-D1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.
Period 1 STARTED	7	7	7	7	7
Period 1 COMPLETED	7	7	7	7	7
Period 1 NOT COMPLETED	0	0	0	0	0
Period 2 STARTED	7	7	7	7	7
Period 2 Not Treated	1	0	0	0	0
Period 2 COMPLETED	7	7	7	7	7
Period 2 NOT COMPLETED	0	0	0	0	0
Period 3 STARTED	7	7	7	7	7
Period 3 COMPLETED	7	7	7	7	7
Period 3 NOT COMPLETED	0	0	0	0	0
Period 4 STARTED	7	7	7	7	7
Period 4 COMPLETED	7	7	7	7	7
Period 4 NOT COMPLETED	0	0	0	0	0
Period 5 STARTED	7	7	7	7	7
Period 5 COMPLETED	7	7	7	7	7
Period 5 NOT COMPLETED	0	0	0	0	0
Period 6 STARTED	7	7	7	7	7
Period 6 COMPLETED	7	7	7	7	7
Period 6 NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bioavailability Study of Five Tablet Formulations of Dabigatran Etexilate Compared to Commercial Capsule Formulation in Healthy Male Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ref-A1-B1-C1-D1-E1 n=7 Participants All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation A1 (TF-A1) in period 2, followed by Test Formulation B1 (TF-B1) in period 3, followed by Test Formulation C1 (TF-C1) in period 4, followed by Test Formulation D1 (TF-D1) in period 5, followed by Test Formulation E1 (TF-E1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.	Ref-B1-C1-D1-E1-A1 n=7 Participants All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation B1 (TF-B1) in period 2, followed by Test Formulation C1 (TF-C1) in period 3, followed by Test Formulation D1 (TF-D1) in period 4, followed by Test Formulation E1 (TF-E1) in period 5, followed by Test Formulation A1 (TF-A1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.	Ref-C1-D1-E1-A1-B1 n=7 Participants All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation C1 (TF-C1) in period 2, followed by Test Formulation D1 (TF-D1) in period 3, followed by Test Formulation E1 (TF-E1) in period 4, followed by Test Formulation A1 (TF-A1) in period 5, followed by Test Formulation B1 (TF-B1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.	Ref-D1-E1-A1-B1-C1 n=7 Participants All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation D1 (TF-D1) in period 2, followed by Test Formulation E1 (TF-E1) in period 3, followed by Test Formulation A1 (TF-A1) in period 4, followed by Test Formulation B1 (TF-B1) in period 5, followed by Test Formulation C1 (TF-C1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.	Ref-E1-A1-B1-C1-D1 n=7 Participants All subjects were treated with the reference treatment (Ref), Dabigatran Etexilate (BIBR 1048) commercial capsule formulation, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours in period 1, followed by one of the 5 investigational treatment in the following sequence, i.e., test formulation Dabigatran Etexilate tablet formulations in the sequence Test Formulation E1 (TF-E1) in period 2, followed by Test Formulation A1 (TF-A1) in period 3, followed by Test Formulation B1 (TF-B1) in period 4, followed by Test Formulation C1 (TF-C1) in period 5, followed by Test Formulation D1 (TF-D1) in period 6, 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours. A washout period of at least 4 days was set following the drug administration in each period.	Total n=35 Participants Total of all reporting groups
Age, Continuous	26.9 Years STANDARD_DEVIATION 2.4 • n=5 Participants	28.1 Years STANDARD_DEVIATION 3.4 • n=7 Participants	27.3 Years STANDARD_DEVIATION 3.4 • n=5 Participants	29.1 Years STANDARD_DEVIATION 3.6 • n=4 Participants	27.4 Years STANDARD_DEVIATION 3.4 • n=21 Participants	27.8 Years STANDARD_DEVIATION 3.2 • n=8 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants	7 Participants n=21 Participants	35 Participants n=8 Participants

PRIMARY outcome

Timeframe: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.

Population: The PharmacoKinetic (PK) parameter analysis Set (PKS): This analysis set included all subjects of the treated set who provided at least one primary or secondary PK parameter. Thus, a subject was included in the PKS, even if the subject contributed only one PK parameter value for one period to the statistical assessment.

This outcome measure presents 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.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate Capsule: Ref n=35 Participants The subjects received Dabigatran Etexilate (Reference) capsule formulation (commercial formulation) 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: A1 n=34 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (A1), 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: B1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (B1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: C1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (C1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: D1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (D1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: E1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (E1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.
AUC0-tz (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)	600 ng*h/mL Geometric Coefficient of Variation 51.8	714 ng*h/mL Geometric Coefficient of Variation 42.1	318 ng*h/mL Geometric Coefficient of Variation 327	354 ng*h/mL Geometric Coefficient of Variation 96.6	649 ng*h/mL Geometric Coefficient of Variation 78.6	661 ng*h/mL Geometric Coefficient of Variation 54.8

PRIMARY outcome

Timeframe: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.

This outcome measure presents maximum concentration of analyte in plasma (Cmax).

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate Capsule: Ref n=35 Participants The subjects received Dabigatran Etexilate (Reference) capsule formulation (commercial formulation) 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: A1 n=34 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (A1), 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: B1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (B1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: C1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (C1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: D1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (D1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: E1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (E1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.
Cmax (Maximum Concentration of Free Dabigatran)	73.5 ng/mL Geometric Coefficient of Variation 60.0	86.8 ng/mL Geometric Coefficient of Variation 39.3	42.3 ng/mL Geometric Coefficient of Variation 213	45.5 ng/mL Geometric Coefficient of Variation 81.5	79.6 ng/mL Geometric Coefficient of Variation 73.5	79.2 ng/mL Geometric Coefficient of Variation 52.7

SECONDARY outcome

Timeframe: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.

Population: The PharmacoKinetic (PK) parameter analysis Set (PKS): Included all subjects of the treated set who provided at least one primary or secondary PK parameter. PK Set 2 (PKS2): Included all subjects in the PKS who had evaluable PK variable of the reference treatment and at least one of the 5 test treatments. PKS2 was used for statistical analyses.

This outcome measure presents area under the concentration-time curve of free Dabigatran in plasma over the time interval from 0 extrapolated to infinity)(if applicable).

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate Capsule: Ref n=35 Participants The subjects received Dabigatran Etexilate (Reference) capsule formulation (commercial formulation) 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: A1 n=34 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (A1), 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: B1 n=31 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (B1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: C1 n=32 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (C1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: D1 n=34 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (D1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: E1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (E1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.
AUC0-infinity (Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity) (if Applicable)	623 ng*h/mL Geometric Coefficient of Variation 49.0	735 ng*h/mL Geometric Coefficient of Variation 40.2	544 ng*h/mL Geometric Coefficient of Variation 71.9	444 ng*h/mL Geometric Coefficient of Variation 60.3	725 ng*h/mL Geometric Coefficient of Variation 53.0	684 ng*h/mL Geometric Coefficient of Variation 51.9

SECONDARY outcome

Timeframe: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.

This outcome measure presents 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.

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate Capsule: Ref n=35 Participants The subjects received Dabigatran Etexilate (Reference) capsule formulation (commercial formulation) 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: A1 n=34 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (A1), 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: B1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (B1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: C1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (C1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: D1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (D1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: E1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (E1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.
AUC0-tz (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)	726 ng*h/mL Geometric Coefficient of Variation 52.9	838 ng*h/mL Geometric Coefficient of Variation 41.1	366 ng*h/mL Geometric Coefficient of Variation 341	412 ng*h/mL Geometric Coefficient of Variation 97.1	777 ng*h/mL Geometric Coefficient of Variation 74.9	778 ng*h/mL Geometric Coefficient of Variation 53.6

SECONDARY outcome

Timeframe: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.

This outcome measure presents maximum concentration of analyte in plasma (Cmax).

Outcome measures

Outcome measures
Measure	Dabigatran Etexilate Capsule: Ref n=35 Participants The subjects received Dabigatran Etexilate (Reference) capsule formulation (commercial formulation) 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: A1 n=34 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (A1), 110 mg orally (one day, single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: B1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (B1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: C1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (C1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: D1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (D1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.	Dabigatran Etexilate Tablet: E1 n=35 Participants The subjects received Dabigatran Etexilate (Test) tablet formulation (E1), 110 mg orally (one day single dose) with 200 mL of water after an overnight fast of at least 10 hours.
Cmax (Maximum Plasma Concentration of Total Dabigatran)	88.6 ng/mL Geometric Coefficient of Variation 62.0	102 ng/mL Geometric Coefficient of Variation 39.0	47.9 ng/mL Geometric Coefficient of Variation 227	52.2 ng/mL Geometric Coefficient of Variation 83.6	94.2 ng/mL Geometric Coefficient of Variation 75.7	91.9 ng/mL Geometric Coefficient of Variation 54.1

SECONDARY outcome

Timeframe: 1:00 [hour (h): minute] before drug administration and 1:00h, 1:30h, 2:00h, 3:00h, 4:00h, 6:00h, 8:00h, 12:00h, 24:00h, 36:00h, 48:00h after drug administration.

This outcome measure presents area under the concentration-time curve of total Dabigatran in plasma over the time interval from 0 extrapolated to infinity)(if applicable).