To investigate and compare safety, pharmacokinetics and pharmacodynamics of BIBR 1048 MS following oral administration of single rising doses from 50 mg to 350 mg in healthy male subjects of Japanese and Caucasian origin. This was the first administration of this substance to subjects of Japanese origin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
Change from baseline in blood pressure (BP)
Time frame: At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration)
Change from baseline in pulse rate (PR)
Time frame: At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration)
Change from baseline in respiratory rate
Time frame: At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration)
Change from baseline in tympanic body temperature
Time frame: At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration)
Change from baseline in 12-Lead electrocardiogram (ECG)
Time frame: At screening (day -14 to -3), at day -1, pre-dose, 2, 48 h after administration and on visit 5 (day 10 to day 14 after administration)
Change from baseline in haematology
Time frame: At screening (day -14 to -3), at day -1 (pre-dose), 48 h after administration and on visit 5 (day 10 to day 14 after administration)
Change from baseline in blood chemistry
Time frame: At screening (day -14 to -3), at day -1 (pre-dose), 48 h after administration and on visit 5 (day 10 to day 14 after administration)
Change from baseline in urinalysis
Time frame: At screening (day -14 to -3), at day -1 (pre-dose), 4, 8, 12, 24, 36, 48 h after administration and on visit 5 (day 10 to day 14 after administration)
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Occurence of adverse events
Time frame: Up to visit 5 (day 10 - 14)
Cmax (maximum concentration of the analyte in plasma)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
tmax (time from dosing to maximum concentration)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable point)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
λz (terminal rate constant in plasma)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
t1/2 (terminal half-life of the analyte in plasma)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
MRTpo (mean residence time of the analyte in the body after po administration)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
(Pharmacokinetic parameters)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to time point t2)
Time frame: pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36 and 36-48 h after administration
fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2)
Time frame: pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36 and 36-48 h after administration
CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)
Time frame: pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36 and 36-48 h after administration
Change from baseline for activated Partial Thromboplastin Time (aPTT)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
Change from baseline for Ecarin clotting time (ECT)
(Pharmacodynamic parameters)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
Change from baseline for thrombin time (TT)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration
Change from baseline for international normalised ratio (INR)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration