Relative Bioavailability of Single Oral Doses of Dabigatran Etexilate With or Without Oral Administration of Verapamil in Two Different Dosages in Healthy Male and Female Volunteers
- Registration Number
- NCT02171533
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
To investigate whether and to what extent the P-glycoprotein inhibitor (P-gp) verapamil affects the pharmacokinetic parameters of dabigatran with verapamil given at different dosages, in different formulations (immediate release (IR) and extended release (ER)), and in different intervals in relation to the dabigatran dose.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Fixed sequence Verapamil Treatments will be given in a fixed sequence Crossover Verapamil ER Treatments will be given in randomized sequences Fixed sequence dabigatran Treatments will be given in a fixed sequence Crossover Verapamil Treatments will be given in randomized sequences Crossover dabigatran Treatments will be given in randomized sequences
- Primary Outcome Measures
Name Time Method AUC0-infinity (area under the concentration-time curve of total dabigatran over the time interval from 0 extrapolated to infinity) up to 107 hours Cmax (maximum measured concentration of total dabigatran) up to 107 hours
- Secondary Outcome Measures
Name Time Method Occurence of Adverse Events within 5 days after last drug administration Cmax (maximum measured concentration of free dabigatran) up to 107 hours AUC0-infinity (area under the concentration-time curve of free dabigatran over the time interval from 0 extrapolated to infinity) up to 107 hours t1/2 (terminal half-life of the analyte in plasma) up to 107 hours Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) up to 107 hours tmin,ss (time from last dosing to the minimum concentration of verapamil at steady state over a uniform dosing interval τ) up to 107 hours Cpre,ss (predose concentration of verapamil at steady state immediately before administration of the next dose) up to 107 hours Cavg (Average concentration of verapamil at steady state) up to 107 hours MRTpo,ss (mean residence time of verapamil in the body at steady state after oral administration) up to 107 hours Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration) up to 107 hours Ae0-24 (amount of dabigatran that is eliminated in urine from the time interval 0-24h) up to 107 hours fe0-24 (fraction of administered drug excreted unchanged in urine from time point 0- 24h) up to 107 hours CLR0-24 (renal clearance of dabigatran from the time point 0 until the time point 24h ) up to 107 hours AUEC0-24 (area under the effect curve) up to 107 hours for ecarin clotting time and thrombin time
ERmax (maximum effect ratio) up to 107 hours for ecarin clotting time and thrombin time
AUC0-infinity (area under the concentration-time curve of verapamil over the time interval from 0 extrapolated to infinity) up to 107 hours Cmax (maximum measured concentration of verapamil) up to 107 hours tmax (time from dosing to the maximum concentration of the analyte in plasma) up to 107 hours λz (terminal rate constant in plasma) up to 107 hours AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 h after the administration) up to 107 hours AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) up to 107 hours MRTpo (mean residence time of the analyte in the body after oral administration) up to 107 hours CL/F (apparent clearance of the analyte in the plasma after extravascular administration) up to 107 hours AUC0-tz,ss (area under the concentration-time curve of verapamil from the time point 0 after the last dose at steady state to the last quantifiable analyte plasma concentration within the uniform dosing interval τ) up to 107 hours Cmax,ss (maximum concentration of verapamil at steady state) up to 107 hours tz,ss (time of last measureable concentration of verapamil within the dosing interval τ at steady state) up to 107 hours tmax,ss (time from last dosing to the maximum concentration of verapamil at steady state on day 4) up to 107 hours CL/F,ss (apparent clearance of verapamil at steady state after extravascular multiple dose administration) up to 107 hours Cmin,ss (minimum measured concentration of verapamil at steady state over a uniform dosing interval τ) up to 107 hours AUCτ,ss (area under the concentration-time curve of verapamil within the uniform dosing interval τ) up to 107 hours Assessment of Tolerability by investigator within 5 days after last drug administration