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

Healthy Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01688830
• Other study ID #: 1321.1
• Secondary ID: 2012-003611-66
• Status: Completed
• Phase: Phase 1
• First received: September 17, 2012
• Last updated: January 15, 2016
• Start date: September 2012
• Est. completion date: November 2013

Study information

• Verified date: January 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal and Health Products
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion criteria:

1. Healthy male subjects

Exclusion criteria:

1. Any relevant deviation from healthy conditions

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Dabigatran

• BI 655075

• Placebo

Locations

Country	Name	City	State
Belgium	1321.1.1 Boehringer Ingelheim Investigational Site	Antwerpen

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

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