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To investigate the relative bioavailability of dabigatran with and without concomitant administration of diclofenac and the relative bioavailability of diclofenac with and without concomitant administration of dabigatran etexilate
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dabigatran etexilate | Active Comparator |
| |
| Diclofenac | Active Comparator |
| |
| Dabigatran etexilate + diclofenac | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dabigatran etexilate | Drug |
| ||
| Diclofenac |
| Measure | Description | Time Frame |
|---|---|---|
| AUCτ,ss on Day 4 (area under the concentration-time curve of dabigatran in plasma at steady state over one dosing interval) | from pre-dose up to 72 hours post-dose | |
| Cmax,ss (maximum concentration of dabigatran in plasma at steady state) | from pre-dose up to 72 hours post-dose | |
| Cmax (maximal concentration of diclofenac in plasma) | from pre-dose up to 72 hours post-dose | |
| AUC0-infinity (area under the concentration-time curve of diclofenac in plasma extrapolated to infinity) | from pre-dose up to 72 hours post-dose | |
| aPTT (activated partial thromboplastin time) and ECT (Ecarin clotting time) with and without diclofenac | from pre-dose up to 72 hours post-dose | |
| AUERτ,ss (area under the effect ratio-time curve of dabigatran in plasma at steady state over a uniform dosing interval τ) | from pre-dose up to 72 hours post-dose | |
| ERmax,ss (maximal effect ratio of dabigatran in plasma at steady state) | from pre-dose up to 72 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-tz,ss (area under the concentration-time curve of dabigatran in plasma from the time point 0 after the last dose at steady state to the last quantifiable dabigatran plasma concentration within the uniform dosing interval τ) | from pre-dose up to 72 hours post-dose | |
| tz,ss (time of last measurable concentration of dabigatran in plasma within the dosing interval τ at steady state) |
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Inclusion criteria:
Exclusion criteria:
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| Drug |
|
| from pre-dose up to 72 hours post-dose |
| tmax,ss (time from last dosing to the maximum concentration of dabigatran in plasma at steady state on Day 4) | from pre-dose up to 72 hours post-dose |
| CL/Fss (apparent clearance of dabigatran in the plasma at steady state after extravascular multiple dose administration) | from pre-dose up to 72 hours post-dose |
| CLR,ss (renal clearance of dabigatran at steady state determined over the dosing interval τ) | from pre-dose up to 72 hours post-dose |
| C min,ss (minimum measured concentration of dabigatran in plasma at steady state over a uniform dosing interval τ) | from pre-dose up to 72 hours post-dose |
| tmin,ss (time from last dosing to the minimum concentration of dabigatran in plasma at steady state over a uniform dosing interval τ) | from pre-dose up to 72 hours post-dose |
| Cpre,ss (pre-dose concentration of dabigatran in plasma at steady state immediately before administration of the next dose) | from pre-dose up to 72 hours post-dose |
| MRTp.o.,ss (mean residence time of dabigatran in the body at steady state after oral administration) | from pre-dose up to 72 hours post-dose |
| Vz/Fss (apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration) | from pre-dose up to 72 hours post-dose |
| Aeτ,ss (amount of dabigatran that is eliminated in urine at steady state over a uniform dosing interval τ) | 0 to 12 h and 12 to 24 h after administration on day 4 |
| feτ,ss (fraction of parent drug eliminated in urine at steady state over a uniform dosing interval τ) | 0 to 12 h and 12 to 24 h after administration on day 4 |
| AUC0-tz (area under the concentration-time curve of diclofenac and 4´- hydroxydiclofenac in plasma over the time interval 0 to the last quantifiable analyte plasma concentration after single dose administration) | from pre-dose up to 72 hours post-dose |
| tz (time of last measurable concentration of diclofenac and 4´- hydroxydiclofenac in plasma following a single dose) | from pre-dose up to 72 hours post-dose |
| %AUCtz-infinity (percentage of the AUC0-infinity that is obtained by extrapolation) for diclofenac and 4´- hydroxydiclofenac | from pre-dose up to 72 hours post-dose |
| tmax (time from dosing to the maximum concentration of diclofenac and 4´- hydroxydiclofenac in plasma following a single dose) | from pre-dose up to 72 hours post-dose |
| λz (terminal rate constant in plasma after a single dose) for diclofenac and 4´- hydroxydiclofenac | from pre-dose up to 72 hours post-dose |
| t1/2 (terminal half-life of diclofenac and 4´- hydroxydiclofenac in plasma after a single dose) | from pre-dose up to 72 hours post-dose |
| MRTp.o. (mean residence time of diclofenac and 4´- hydroxydiclofenac in the body after single dose oral administration) | from pre-dose up to 72 hours post-dose |
| CL/F (apparent clearance of diclofenac and 4´- hydroxydiclofenac in the plasma after extravascular single dose administration) | from pre-dose up to 72 hours post-dose |
| Vz/F (apparent volume of distribution during the terminal phase λz following extravascular dose) for diclofenac and 4´- hydroxydiclofenac | from pre-dose up to 72 hours post-dose |
| ID | Term |
|---|---|
| D000069604 | Dabigatran |
| D004008 | Diclofenac |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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