Healthy
Conditions
Brief summary
To investigate the pharmacokinetic and pharmacodynamic interaction of dabigatran and ticagrelor under steady state conditions; to investigate the effect of staggered administration of ticagrelor loading dose on dabigatran exposure (in Part II)
Interventions
DRUGdabigatran etexilate
multiple doses of dabigatran
DRUGticagrelor
loading dose of ticagrelor
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_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
1\. Any relevant deviation from healthy conditions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss) | 47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours | Area under the concentration-time curve of dabigatran etexilate in plasma at steady state over the uniform dosing interval τ (AUCτ,ss). |
| Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss) | 47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours | Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss). |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 In part 1, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, ticagrelor treatment was added starting with the concomitant administration of a 180 mg ticagrelor loading dose followed by 90 mg ticagrelor twice daily. Dabigatran PK profiles were taken on day 1 of the test treatment and day 4 of the test treatment. | 24 |
| Part 2 In part 2, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, 180 mg ticagrelor were given 2 hours after the morning dose of 110 mg dabigatran etexilate and dabigatran PK profile were taken on this day 1 of the test treatment. | 24 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1 | Part 2 | Total |
|---|---|---|---|
| Age, Continuous | 28.0 years STANDARD_DEVIATION 7.2 | 28.6 years STANDARD_DEVIATION 7.1 | 28.3 years STANDARD_DEVIATION 7.15 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 24 Participants | 24 Participants | 48 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 23 | 0 / 23 | 2 / 24 | 0 / 21 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 | 0 / 23 | 0 / 24 | 0 / 21 |
Outcome results
Primary
Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss)
Area under the concentration-time curve of dabigatran etexilate in plasma at steady state over the uniform dosing interval τ (AUCτ,ss).
Time frame: 47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours
Population: Pharmacokinetic set: This subject set included all subjects in the TS who provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability and who had not vomiting at or before 2 times the median tmax,ss of the trial medications on PK study days of both trial parts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigratan Etexilate 110mg Bid Alone - Part 1 | Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss) | 551 ng*h/mL | Geometric Coefficient of Variation 59 |
| Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 1 | Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss) | 817 ng*h/mL | Geometric Coefficient of Variation 43.3 |
| Dabigatran Etexilate 110mg Bid + Ticagrelor 90mg Bid - Part 1 | Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss) | 689 ng*h/mL | Geometric Coefficient of Variation 55.1 |
| Dabigratan Etexilate 110mg Bid Alone - Part 2 | Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss) | 660 ng*h/mL | Geometric Coefficient of Variation 39.6 |
| Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 2 | Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss) | 844 ng*h/mL | Geometric Coefficient of Variation 43.4 |
p-value: 0.945690% CI: [124.388, 179.383]ANOVA
p-value: 0.548190% CI: [107.363, 148.967]ANOVA
p-value: 0.566590% CI: [108.047, 149.295]ANOVA
Primary
Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss)
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss).
Time frame: 47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours
Population: Pharmacokinetic set: This subject set included all subjects in the TS who provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability and who had not vomiting at or before 2 times the median tmax,ss of the trial medications on PK study days of both trial parts.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dabigratan Etexilate 110mg Bid Alone - Part 1 | Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss) | 83.6 ng/mL | Geometric Coefficient of Variation 69.3 |
| Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 1 | Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss) | 136 ng/mL | Geometric Coefficient of Variation 45.4 |
| Dabigatran Etexilate 110mg Bid + Ticagrelor 90mg Bid - Part 1 | Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss) | 106 ng/mL | Geometric Coefficient of Variation 65.1 |
| Dabigratan Etexilate 110mg Bid Alone - Part 2 | Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss) | 97.6 ng/mL | Geometric Coefficient of Variation 46.5 |
| Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 2 | Total Dabigatran: Maximum Measured Concentration at Steady State (Cmax,ss) | 121 ng/mL | Geometric Coefficient of Variation 45.2 |
p-value: 0.984190% CI: [133.945, 202.619]ANOVA
p-value: 0.600390% CI: [106.37, 155.495]ANOVA
p-value: 0.465690% CI: [102.695, 149.288]ANOVA