Healthy
Conditions
Brief summary
Evaluation of potential ticagrelor effects on dabigatran exposure and evaluation of two new pharmacodynamic methods
Interventions
DRUGdabigatran etexilate
medium dose dabigatran
DRUGTicagrelor
high dose ticagrelor
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male subjects
Exclusion criteria
2. Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Dabigatran (Dabi): Area Under the Curve 0 to Infinity (AUC0-∞) | -1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours | Area under the concentration-time curve of the analyte in plasma, over the time interval from 0 extrapolated to infinity, of dabigatran. |
| Total Dabigatran: Maximum Measured Concentration (Cmax) | -1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours | Maximum measured concentration of total dabigatran in plasma, per period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Drug Related Adverse Events | From screening until the end-of-study examination | The number of participants with drug related adverse events |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran Etexilate 220 mg - Part 1 A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a washed blood test. | 8 |
| Ticagrelor 180 mg - Part 1 A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a washed blood test. | 4 |
| Dabigatran Etexilate 220 mg - Part 2 A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a shed blood test. | 8 |
| Ticagrelor 180 mg - Part 2 A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a shed blood test | 4 |
| Dabigatran Etexilate / Multiple Dose Ticagrelor - Part 3 A randomised two-period cross-over trial, the two treatments administered were
* A single dose of dabigatran etexilate 75 mg
* Ticagrelor coated tablets dosed for four days; 180 mg loading dose on day 1, 90 mg twice daily on day 2 and 3, 90 mg on day 4. Co-administered with a single dose of 75 mg Dabigatran etexilate on days 1 and 4.
Between treatment periods there was a washout period of at least 4 days. | 12 |
| Total | 36 |
Baseline characteristics
| Characteristic | Dabigatran Etexilate 220 mg - Part 1 | Ticagrelor 180 mg - Part 1 | Dabigatran Etexilate 220 mg - Part 2 | Ticagrelor 180 mg - Part 2 | Dabigatran Etexilate / Multiple Dose Ticagrelor - Part 3 | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 30.6 years STANDARD_DEVIATION 7.7 | 29.8 years STANDARD_DEVIATION 11.4 | 33.6 years STANDARD_DEVIATION 9.1 | 33.3 years STANDARD_DEVIATION 6.3 | 30.2 years STANDARD_DEVIATION 7.2 | 31.3 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 8 Participants | 4 Participants | 12 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 8 | 0 / 4 | 0 / 8 | 0 / 4 | 2 / 12 | 3 / 12 |
| serious Total, serious adverse events | 0 / 8 | 0 / 4 | 0 / 8 | 0 / 4 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Total Dabigatran (Dabi): Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of the analyte in plasma, over the time interval from 0 extrapolated to infinity, of dabigatran.
Time frame: -1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours
Population: Pharmacokinetic (PK) set defined as all subjects of Part 3 who received at least 1 dose of trial medication and provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabi 75 mg | Total Dabigatran (Dabi): Area Under the Curve 0 to Infinity (AUC0-∞) | 281.05 ng*h/mL | Geometric Coefficient of Variation 104 |
| Dabi + Ticagrelor LD | Total Dabigatran (Dabi): Area Under the Curve 0 to Infinity (AUC0-∞) | 485.48 ng*h/mL | Geometric Coefficient of Variation 40.5 |
| Dabi + Ticagrelor MD | Total Dabigatran (Dabi): Area Under the Curve 0 to Infinity (AUC0-∞) | 410.46 ng*h/mL | Geometric Coefficient of Variation 53.1 |
Primary
Total Dabigatran: Maximum Measured Concentration (Cmax)
Maximum measured concentration of total dabigatran in plasma, per period.
Time frame: -1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours
Population: Pharmacokinetic (PK) set defined as all subjects of Part 3 who received at least 1 dose of trial medication and provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabi 75 mg | Total Dabigatran: Maximum Measured Concentration (Cmax) | 31.47 ng/mL | Geometric Coefficient of Variation 130 |
| Dabi + Ticagrelor LD | Total Dabigatran: Maximum Measured Concentration (Cmax) | 61.30 ng/mL | Geometric Coefficient of Variation 42.9 |
| Dabi + Ticagrelor MD | Total Dabigatran: Maximum Measured Concentration (Cmax) | 49.11 ng/mL | Geometric Coefficient of Variation 64.8 |
Secondary
Number of Participants With Drug Related Adverse Events
The number of participants with drug related adverse events
Time frame: From screening until the end-of-study examination
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dabi 75 mg | Number of Participants With Drug Related Adverse Events | 0 participants |
| Dabi + Ticagrelor LD | Number of Participants With Drug Related Adverse Events | 0 participants |
| Dabi + Ticagrelor MD | Number of Participants With Drug Related Adverse Events | 0 participants |
| Ticagrelor 180 mg - Part 2 | Number of Participants With Drug Related Adverse Events | 0 participants |
| Dabigatran 75 mg - Part 3 | Number of Participants With Drug Related Adverse Events | 0 participants |
| Dabigatran + Ticagrelor - Part 3 | Number of Participants With Drug Related Adverse Events | 1 participants |