Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BI 655075 Administered Alone or With Dabigatran Etexilate

Study Overview
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Brief Summary
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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.

Official Title
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Randomised, Double-blind, Placebo-controlled Phase I Study in Healthy Male Volunteers. to Investigate Safety, Tolerability and Pharmacokinetics of Single Rising Doses of BI 655075 (Part 1) and to Explore the Dose of BI 655075 Effective to Reverse Dabigatran Anticoagulant Activity (Part 2)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dabigatran
* Drug: BI 655075
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 1. Healthy male subjects Exclusion criteria: 1. Any relevant deviation from healthy conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 655075<br> | Drug: BI 655075<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Experimental: BI 655075 with dabigatran<br> | Drug: Dabigatran<br> <br> Drug: BI 655075<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Drug Related Adverse Events (AE) | Frequency of subjects with related adverse events (AE) by treatment | AEs occurring until end of follow-up (Up to 3 months after last drug administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (Maximum Measured Concentration) for Idarucizumab | 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 | 
| Tmax (Time From Dosing to Maximum Measured Concentration) for Idarucizumab | 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 | 
| 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 | -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. | 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 | 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 | 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. | 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 | 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) | 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) | 2hours-12 hours |