The primary objective is to investigate the safety, tolerability and pharmacokinetics of BI 655075 following intravenous administration of single rising doses of BI 655075 when administered alone and after administration of dabigatran.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
157
1321.1.1 Boehringer Ingelheim Investigational Site
Antwerp, Belgium
Number of Subjects With Drug Related Adverse Events (AE)
Frequency of subjects with related adverse events (AE) by treatment
Time frame: AEs occurring until end of follow-up (Up to 3 months after last drug administration)
Cmax (Maximum Measured Concentration) for Idarucizumab
Cmax (maximum measured concentration) for idarucizumab
Time frame: -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h
Tmax (Time From Dosing to Maximum Measured Concentration) for Idarucizumab
tmax (time from dosing to maximum measured concentration) for idarucizumab
Time frame: -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h
AUC0-inf (Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity) for Idarucizumab
AUC0-inf (area under the concentration-time curve from time 0 extrapolated to infinity) for idarucizumab
Time frame: -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h
Aet1-t2 (Amount of Idarucizumab Eliminated in Urine From Time Point t1 to Time Point t2)
Aet1-t2 (amount of idarucizumab eliminated in urine from time point t1 to time point t2) Ae(0-7h) is presented for dose groups with 1 h infusion and Ae(0-4h) is presented for dose groups with 5 min infusion.
Time frame: Up to 7 hours
Aet1-t2,ss (Amount of Dabigatran Etexilate Eliminated in Urine From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4 for Sum Dabigatran
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Aet1-t2,ss (amount of dabigatran etexilate eliminated in urine from time point t1 to time point t2, at steady state) on Day 3 and Day 4 Ae(0-12h,ss) of sum dabigatran
Time frame: Intervals 0-2, 2-6, 6-10, 10-12 hours on Day 3 post dabigatran treatment and -2 to -0:05, -0:05 to 4, 4-8, 8-10, 10-12, 12-24, 24-48, 48-72 on Day 4 post Idarucizumab treatment
C1.92,ss, C2,ss, C2.5,ss, C6,ss, and C12,ss (Concentration of the Unbound Sum Dabigatran in Plasma at Steady State)
Concentrations of unbound sum dabigatran in plasma after 1.92 to 12 h, at steady state of dabigatran, on Day 4 are presented. The endpoint refers to unbound sum dabigatran at several time points. The intended pharmacodynamic effect of idarucizumab is to reduce the concentration of this measure to levels below the lower limit of quantification (BLQ). "BLQ" values are not considered in the calculation of descriptive statistics; and therefore bias the result. This is the reason for applying the 2/3 rule to obtain reliable results. 2/3 rule states that, Statistics of PK parameters are only estimated when at least 2/3 of the data are evaluable.
Time frame: 1.92 hours (h), 2 h, 2.5 h, 6 h and 12 h on Day 4
AUCt1-t2,ss (Area Under the Concentration-time Curve for the Unbound Sum Dabigatran in Plasma From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4
AUC(2-12),ss ((area under the concentration-time curve for the idarucizumab in plasma from time point 2 to 12 h )) on Day 3 and Day 4
Time frame: 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h
AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 2 of the Study
AUECt1-t2 (area under the effect curve from time point t1=2 hours to time point t2=12 hours) on Day 3 and Day 4 (determined under consideration of the baseline value). Ratio of above baseline AUEC(2-12) on Day 4 to above baseline AUEC(2-12) on Day 3 is presented. This endpoint was determined for Activated Partial Thromboplastin time (aPTT), Dithiothreitol (dTT), Thrombin time (TT) and Ecarin clotting time (ECT)
Time frame: 2hours-12 hours
AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 3 of the Study
AUECt1-t2 (area under the effect curve from time point t1=2 hours to time point t2=12 hours) on Day 3 and Day 4 (determined under consideration of the baseline value). Ratio of above baseline AUEC(2-12) on Day 4 to above baseline AUEC(2-12) on Day 3 is presented. This endpoint was determined for Activated Partial Thromboplastin time (aPTT) and Dithiothreitol (dTT)
Time frame: 2hours-12 hours