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Relative Bioavailability of Dabigatran and Diclofenac After Dabigatran Etexilate and Diclofenac Single Dose Alone or Following Concomitant Multiple Oral Administrations in Healthy Male and Female Volunteers

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT02171507
Lead Sponsor
Boehringer Ingelheim
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Dabigatran etexilateDabigatran etexilate-
DiclofenacDiclofenac-
Dabigatran etexilate + diclofenacDabigatran etexilate-
Dabigatran etexilate + diclofenacDiclofenac-
Primary Outcome Measures
NameTimeMethod
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 diclofenacfrom 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
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
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
Secondary Outcome Measures
NameTimeMethod
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
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
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
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
tz,ss (time of last measurable concentration of dabigatran in plasma within the dosing interval τ at steady state)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´- hydroxydiclofenacfrom 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´- hydroxydiclofenacfrom 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´- hydroxydiclofenacfrom pre-dose up to 72 hours post-dose
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