Trial Outcomes & Findings for Pradaxa Tablet Proton Pump Inhibitor (PPI) Bioavailability (BA) Study in Japan (NCT NCT03143166)
NCT ID: NCT03143166
Last Updated: 2019-01-16
Results Overview
This endpoint calculates area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 to the time of last quantifiable time point.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.
Results posted on
2019-01-16
Participant Flow
This was open label, 2 period, fixed sequence (RT), single arm study in 36 healthy male Japanese subjects. All subjects were orally treated with single dose of 110 milligram (mg) dabigatran etexilate (DE) tablet formulation alone in period 1 and with 20 mg rabeprazole tablet in period 2 with 4 days of rabeprazole pre-medication.
After it had been determined that the subject met all eligibility criteria, a unique subject number was assigned. The number was recorded on electronic Case Report Forms and correspondence regarding the subject. Once a subject number had been assigned, it could not be reassigned to any other subject. Randomisation was not planned in this study.
Participant milestones
| Measure |
Dabigatran Etexilate 110 mg With and Without Rabeprazole 20 mg
Subjects were treated orally with dabigatran etexilate 110 mg tablet alone (Reference) after an overnight fast of at least 10 hours (h) without pretreatment with rabeprazole 20 mg tablet in period 1 followed by single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets (Test) once daily with 4 days of rabeprazole pre-treatment in period 2. The treatments of dabigatran etexilate were separated by a wash-out phase of at least 4 days.
|
|---|---|
|
Period 1
STARTED
|
36
|
|
Period 1
COMPLETED
|
36
|
|
Period 1
NOT COMPLETED
|
0
|
|
Period 2 (Washout of at Least 4 Days)
STARTED
|
36
|
|
Period 2 (Washout of at Least 4 Days)
COMPLETED
|
35
|
|
Period 2 (Washout of at Least 4 Days)
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Dabigatran Etexilate 110 mg With and Without Rabeprazole 20 mg
Subjects were treated orally with dabigatran etexilate 110 mg tablet alone (Reference) after an overnight fast of at least 10 hours (h) without pretreatment with rabeprazole 20 mg tablet in period 1 followed by single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets (Test) once daily with 4 days of rabeprazole pre-treatment in period 2. The treatments of dabigatran etexilate were separated by a wash-out phase of at least 4 days.
|
|---|---|
|
Period 2 (Washout of at Least 4 Days)
Withdrawal by Subject
|
1
|
Baseline Characteristics
TS
Baseline characteristics by cohort
| Measure |
Total Subjects
n=36 Participants
Subjects were treated orally with dabigatran etexilate 110 mg tablet alone (Reference) after an overnight fast of at least 10 hours (h) without pretreatment with rabeprazole 20 mg tablet in period 1 followed by single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets (Test) once daily with 4 days of rabeprazole pre-treatment in period 2. The treatments of dabigatran etexilate were separated by a wash-out phase of at least 4 days.
|
|---|---|
|
Age, Continuous
|
26.3 Years
STANDARD_DEVIATION 4.7 • n=5 Participants • TS
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants • TS
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants • TS
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants • TS
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
36 Participants
n=5 Participants • TS
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
Asian
|
36 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants • TS
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants • TS
|
PRIMARY outcome
Timeframe: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.Population: Pharmacokinetic set (PKS): All treated subjects who provided at least 1 observation for at least 1 primary endpoint without important protocol violations with respect to the statistical evaluation of Pharmacokinetic (PK) endpoints were included in PKS.
This endpoint calculates area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 to the time of last quantifiable time point.
Outcome measures
| Measure |
Dabigatran Etexilate 110 mg (Reference)
n=36 Participants
Subjects were treated orally with dabigatran etexilate 110 mg tablet alone after an overnight fast of at least 10 hours (h) without pre-treatment with rabeprazole 20 mg tablet.
|
Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
n=35 Participants
Subjects were treated orally with single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets once daily with 4 days of rabeprazole pre-treatment.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Total Dabigatran (AUC0-tz).
|
667 Nanogram*Hour/ millilitre (ng*h/mL)
Geometric Coefficient of Variation 123
|
192 Nanogram*Hour/ millilitre (ng*h/mL)
Geometric Coefficient of Variation 109
|
PRIMARY outcome
Timeframe: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.Population: PKS
This outcome is maximum measured concentration of the total dabigatran in plasma
Outcome measures
| Measure |
Dabigatran Etexilate 110 mg (Reference)
n=36 Participants
Subjects were treated orally with dabigatran etexilate 110 mg tablet alone after an overnight fast of at least 10 hours (h) without pre-treatment with rabeprazole 20 mg tablet.
|
Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
n=35 Participants
Subjects were treated orally with single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets once daily with 4 days of rabeprazole pre-treatment.
|
|---|---|---|
|
Maximum Concentration of Total Dabigatran in Plasma (Cmax).
|
83.1 Nano gram per milliliter (ng/mL)
Geometric Coefficient of Variation 118
|
21.8 Nano gram per milliliter (ng/mL)
Geometric Coefficient of Variation 105
|
SECONDARY outcome
Timeframe: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.Population: PKS
This endpoint calculates area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 to the time of last quantifiable time point.
Outcome measures
| Measure |
Dabigatran Etexilate 110 mg (Reference)
n=36 Participants
Subjects were treated orally with dabigatran etexilate 110 mg tablet alone after an overnight fast of at least 10 hours (h) without pre-treatment with rabeprazole 20 mg tablet.
|
Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
n=35 Participants
Subjects were treated orally with single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets once daily with 4 days of rabeprazole pre-treatment.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 to Time of Last Quantifiable Time Point (tz) of Free Dabigatran (AUC0-tz).
|
588 Nanogram*Hour/ millilitre (ng*h/mL)
Geometric Coefficient of Variation 119
|
164 Nanogram*Hour/ millilitre (ng*h/mL)
Geometric Coefficient of Variation 110
|
SECONDARY outcome
Timeframe: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.Population: PKS
This outcome is maximum measured concentration of the free dabigatran in plasma
Outcome measures
| Measure |
Dabigatran Etexilate 110 mg (Reference)
n=36 Participants
Subjects were treated orally with dabigatran etexilate 110 mg tablet alone after an overnight fast of at least 10 hours (h) without pre-treatment with rabeprazole 20 mg tablet.
|
Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
n=35 Participants
Subjects were treated orally with single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets once daily with 4 days of rabeprazole pre-treatment.
|
|---|---|---|
|
Maximum Concentration of Free Dabigatran in Plasma (Cmax).
|
72.9 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 114
|
20.0 Nanogram per milliliter (ng/mL)
Geometric Coefficient of Variation 103
|
SECONDARY outcome
Timeframe: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.Population: PKS
This endpoint calculates area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity
Outcome measures
| Measure |
Dabigatran Etexilate 110 mg (Reference)
n=36 Participants
Subjects were treated orally with dabigatran etexilate 110 mg tablet alone after an overnight fast of at least 10 hours (h) without pre-treatment with rabeprazole 20 mg tablet.
|
Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
n=35 Participants
Subjects were treated orally with single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets once daily with 4 days of rabeprazole pre-treatment.
|
|---|---|---|
|
Area Under the Concentration-time Curve of Total Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).
|
702 Nanogram*Hour/ millilitre (ng*h/mL)
Geometric Coefficient of Variation 110
|
214 Nanogram*Hour/ millilitre (ng*h/mL)
Geometric Coefficient of Variation 96.6
|
SECONDARY outcome
Timeframe: Samples were collected 1 hour Pre-dose and at 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00 36:00 and 48:00 hours post dose.Population: PKS
This endpoint calculates area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity.
Outcome measures
| Measure |
Dabigatran Etexilate 110 mg (Reference)
n=36 Participants
Subjects were treated orally with dabigatran etexilate 110 mg tablet alone after an overnight fast of at least 10 hours (h) without pre-treatment with rabeprazole 20 mg tablet.
|
Dabigatran Etexilate 110 mg + Rabeprazole 20 mg Tablet (Test)
n=35 Participants
Subjects were treated orally with single dose of dabigatran etexilate 110 mg tablet and rabeprazole 20 mg tablets once daily with 4 days of rabeprazole pre-treatment.
|
|---|---|---|
|
Area Under the Concentration-time Curve of Free Dabigatran in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).
|
618 Nanogram*Hour/ millilitre (ng*h/mL)
Geometric Coefficient of Variation 107
|
188 Nanogram*Hour/ millilitre (ng*h/mL)
Geometric Coefficient of Variation 93.4
|
Adverse Events
Dabigatran Etexilate 110 mg (Reference)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Dabigatran Etexilate 110 mg + Rabeprazole 20 mg (Test)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER