Trial Outcomes & Findings for Relative Bioavailability of Dabigatran Capsules, Pellets and Oral Solution in Healthy Volunteers (NCT NCT02044367)
NCT ID: NCT02044367
Last Updated: 2015-05-20
Results Overview
Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t for total dabigatran.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
54 participants
Primary outcome timeframe
47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administration
Results posted on
2015-05-20
Participant Flow
Participant milestones
| Measure |
T1-T2-R
T1: pellets on food; T2: granules for reconstitution into solution; R: hard capsule. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T1-R-T2
T1: pellets on food; R: hard capsule; T2: granules for reconstitution into solution. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T2-T1-R
T2: granules for reconstitution into solution; T1: pellets on food; R: hard capsule. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T2-R-T1
T2: granules for reconstitution into solution; R: hard capsule; T1: pellets on food. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
R-T1-T2
R: hard capsule; T1: pellets on food; T2: granules for reconstitution into solution. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
R-T2-T1
R: hard capsule; T2: granules for reconstitution into solution; T1: pellets on food. The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
9
|
9
|
9
|
9
|
|
Overall Study
COMPLETED
|
9
|
9
|
9
|
9
|
9
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Relative Bioavailability of Dabigatran Capsules, Pellets and Oral Solution in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Overall
n=54 Participants
A randomised, open-label, 3-way crossover, multiple dose trial consisting of 3 identical treatment periods of 3 days. Study drug (150 mg dabigatran etexilate) was administrated twice daily on Day 1 and Day 2 and once on Day 3. The dosage forms used were: hard capsule, granules resolved in reconstitution solution and pellets on food. Treatment periods were separated by a washout phase of at least 5 days between last drug administration of one treatment and the first drug administration of the next treatment.
|
|---|---|
|
Age, Continuous
|
36.2 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
54 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administrationPopulation: Pharmacokinetic analysis set (PKS) included all treated subjects that provided at least 1 observation for at least 1 primary or secondary PK endpoint without relevant protocol deviations with respect to the statistical evaluation of PK endpoints.
Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t for total dabigatran.
Outcome measures
| Measure |
T1 (Treatment A)
n=54 Participants
multiple dose of dabigatran (Pellets)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T2 (Treatment B)
n=54 Participants
multiple dose of dabigatran (Granules resolved in reconstitution solution)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
R (Reference)
n=53 Participants
multiple dose of dabigatran (Hard capsule)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran.
|
1220 ng∙h/mL
Geometric Coefficient of Variation 34.1
|
1160 ng∙h/mL
Geometric Coefficient of Variation 27.0
|
893 ng∙h/mL
Geometric Coefficient of Variation 46.8
|
PRIMARY outcome
Timeframe: 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administrationPopulation: Pharmacokinetic analysis set (PKS) included all treated subjects that provided at least 1 observation for at least 1 primary or secondary PK endpoint without relevant protocol deviations with respect to the statistical evaluation of PK endpoints.
Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t for total dabigatran.
Outcome measures
| Measure |
T1 (Treatment A)
n=54 Participants
multiple dose of dabigatran (Pellets)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T2 (Treatment B)
n=54 Participants
multiple dose of dabigatran (Granules resolved in reconstitution solution)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
R (Reference)
n=53 Participants
multiple dose of dabigatran (Hard capsule)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
|---|---|---|---|
|
Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Total Dabigatran.
|
191 ng/mL
Geometric Coefficient of Variation 37.4
|
184 ng/mL
Geometric Coefficient of Variation 27.3
|
131 ng/mL
Geometric Coefficient of Variation 50.8
|
SECONDARY outcome
Timeframe: 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administrationPopulation: Pharmacokinetic analysis set (PKS) included all treated subjects that provided at least 1 observation for at least 1 primary or secondary PK endpoint without relevant protocol deviations with respect to the statistical evaluation of PK endpoints.
Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t for free dabigatran.
Outcome measures
| Measure |
T1 (Treatment A)
n=54 Participants
multiple dose of dabigatran (Pellets)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T2 (Treatment B)
n=54 Participants
multiple dose of dabigatran (Granules resolved in reconstitution solution)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
R (Reference)
n=53 Participants
multiple dose of dabigatran (Hard capsule)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran.
|
1000 ng*h/mL
Geometric Coefficient of Variation 35.8
|
958 ng*h/mL
Geometric Coefficient of Variation 27.6
|
727 ng*h/mL
Geometric Coefficient of Variation 50.8
|
SECONDARY outcome
Timeframe: 47:55, 48:30, 49:00, 49:30, 50:00, 50:30, 51:00, 51:30, 52:00, 54:00, 56:00, 58:00, 60:00 relative to first drug administrationPopulation: Pharmacokinetic analysis set (PKS) included all treated subjects that provided at least 1 observation for at least 1 primary or secondary PK endpoint without relevant protocol deviations with respect to the statistical evaluation of PK endpoints.
Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t for free dabigatran.
Outcome measures
| Measure |
T1 (Treatment A)
n=54 Participants
multiple dose of dabigatran (Pellets)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T2 (Treatment B)
n=54 Participants
multiple dose of dabigatran (Granules resolved in reconstitution solution)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
R (Reference)
n=53 Participants
multiple dose of dabigatran (Hard capsule)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
|---|---|---|---|
|
Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval t for Free Dabigatran.
|
157 ng/mL
Geometric Coefficient of Variation 37.9
|
154 ng/mL
Geometric Coefficient of Variation 27.6
|
106 ng/mL
Geometric Coefficient of Variation 55.1
|
SECONDARY outcome
Timeframe: once on day 3 (48 hours after first dose)Population: Treated set including all subjects that provided at least 1 observation for at least 1 of the questions for at least 1 of the test products.
Acceptability question: "Would you accept to take this medication for chronic use?" with 3 possible answers: Yes - No - I am not sure.
Outcome measures
| Measure |
T1 (Treatment A)
n=53 Participants
multiple dose of dabigatran (Pellets)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T2 (Treatment B)
n=53 Participants
multiple dose of dabigatran (Granules resolved in reconstitution solution)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
R (Reference)
multiple dose of dabigatran (Hard capsule)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
|---|---|---|---|
|
Acceptability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
Yes
|
37 participants
|
29 participants
|
—
|
|
Acceptability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
No
|
9 participants
|
17 participants
|
—
|
|
Acceptability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
I am not sure
|
7 participants
|
7 participants
|
—
|
SECONDARY outcome
Timeframe: once on day 3 (48 hours after first dose)Population: Treated set including all subjects that provided at least 1 observation for at least 1 of the questions for at least 1 of the test products.
Palatability question: "How do you rank the taste?" with 5 possible answers: Very good - Good - Fair - Acceptable - Not acceptable.
Outcome measures
| Measure |
T1 (Treatment A)
n=53 Participants
multiple dose of dabigatran (Pellets)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T2 (Treatment B)
n=53 Participants
multiple dose of dabigatran (Granules resolved in reconstitution solution)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
R (Reference)
multiple dose of dabigatran (Hard capsule)
The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
|---|---|---|---|
|
Palatability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
Very good
|
2 participants
|
0 participants
|
—
|
|
Palatability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
Good
|
20 participants
|
15 participants
|
—
|
|
Palatability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
Fair
|
18 participants
|
17 participants
|
—
|
|
Palatability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
Acceptable
|
11 participants
|
14 participants
|
—
|
|
Palatability Rating for Pellets (on Food) and Oral Solution Will be Assessed by Asking the Subjects 1 Multiple Choice Verbal Question.
Not acceptable
|
2 participants
|
7 participants
|
—
|
Adverse Events
T1 (Treatment A)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
T2 (Treatment B)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
R (Reference)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
T1 (Treatment A)
n=54 participants at risk
multiple dose of dabigatran (Pellets). The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
T2 (Treatment B)
n=54 participants at risk
multiple dose of dabigatran (Granules resolved in reconstitution solution) The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
R (Reference)
n=54 participants at risk
multiple dose of dabigatran (Hard capsule) The treatments were 150 mg dabigatran etexilate twice daily on Days 1 and 2 and once after an overnight fast of at least 10 hours on Day 3 for all treatments T1, T2 and R. All treatments were administered orally with 240 mL of water.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
3.7%
2/54 • First dose of study drug date/time until the end-of-trial examination (last per protocol visit)
|
5.6%
3/54 • First dose of study drug date/time until the end-of-trial examination (last per protocol visit)
|
1.9%
1/54 • First dose of study drug date/time until the end-of-trial examination (last per protocol visit)
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place