Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BI 655075 Administered Alone or With Dabigatran Etexilate
- Registration Number
- NCT01688830
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 157
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BI 655075 with dabigatran Dabigatran - BI 655075 with dabigatran BI 655075 - Placebo Placebo - BI 655075 BI 655075 -
- Primary Outcome Measures
Name Time Method Number of Subjects With Drug Related Adverse Events (AE) AEs occurring until end of follow-up (Up to 3 months after last drug administration) Frequency of subjects with related adverse events (AE) by treatment
- Secondary Outcome Measures
Name Time Method Tmax (Time From Dosing to Maximum Measured Concentration) for Idarucizumab -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
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 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 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 dabigatranAUCt1-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 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h 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
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 2hours-12 hours 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)Cmax (Maximum Measured Concentration) for Idarucizumab -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 Cmax (maximum measured concentration) for idarucizumab
Aet1-t2 (Amount of Idarucizumab Eliminated in Urine From Time Point t1 to Time Point t2) Up to 7 hours 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.C1.92,ss, C2,ss, C2.5,ss, C6,ss, and C12,ss (Concentration of the Unbound Sum Dabigatran in Plasma at Steady State) 1.92 hours (h), 2 h, 2.5 h, 6 h and 12 h on Day 4 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.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 2hours-12 hours 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)AUC0-inf (Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity) for Idarucizumab -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
Trial Locations
- Locations (1)
1321.1.1 Boehringer Ingelheim Investigational Site
🇧🇪Antwerpen, Belgium