Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BI 655075 (Idarucizumab) Administered Alone or With Dabigatran Etexilate in Japanese Healthy Subjects

Healthy Clinical Trial

Official title:

Randomised, Double-blind Within Dose Groups, Placebo-controlled Phase I Trial in Healthy Japanese Male Volunteers to Investigate Safety, Tolerability and Pharmacokinetics of Different Doses of BI 655075 (Part 1) and to Explore the Effective Dose of BI 655075 to Reverse Dabigatran Anticoagulant Activity (Part 2).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02028780
• Other study ID #: 1321.5
• Status: Completed
• Phase: Phase 1
• First received: January 6, 2014
• Last updated: January 13, 2016
• Start date: January 2014
• Est. completion date: August 2014

Study information

• Verified date: January 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• 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: 80
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

Inclusion criteria:

1. Healthy Japanese 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:
• Placebo to dose
placebo
• Idarucizumab
short infusion
• Placebo to Idarucizumab
Placebo to Idarucizumab
• dabigatran
2 capsules dabigatran
• Idarucizumab
short infusion

Locations

Country	Name	City	State
Japan	1321.5.00001 Boehringer Ingelheim Investigational Site	Sumida-ku, Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Drug-related Adverse Events in Part 1 and Part 2	Percentage of subjects with drug-related adverse events in Part 1 and Part 2.	From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)	No
Secondary	Ae0-74,ss on Days 4 and 11 for Sum Dabigatran (Part II)	Amount of analyte eliminated in urine at steady state from the time point 0 hours to time point 74 hours.	0-2 h, 2-6 h, 6-10 h, 10-12 h,12-14h, 14-26 h, 26-50 h, 50-74 h after drug administration of dabigatran etexilate on Day 4 and Day 11.	No
Secondary	AUC2-12,ss on Days 4 and 11 for Unbound Sum Dabigatran (Part II).	Area under the concentration-time curve of the dabigatran in plasma at steady state over the time interval 2 hours-12 hours.; Time Frame: For dose group 5 to 7 (Day 1 to 3-Part-I):74hours (h), 74.5h, 75h, 76h, 78h, 80h, 82h, 84h, For dose group 8 (Day 1 to 3-Part-I): 74h, 74.5h, 75h, 76h, 78h, 80h, 82h, 84h and For dose group 5-7 (Day11 to Day13-Part II):242h, 242.167h, 242.5h, 243h, 244h,246h, 248h, 250h, 252h. For dose group 8 (Day11 to Day13-Part II):242h, 242.083h, 242.25h, 242.333h, 243.333h, 244h, 246h, 248h, 252h.	Day 4 (Part I) and Day 11 (Part II). Time frame are provided in detail in the Description section	No
Secondary	Cmax for Idarucizumab in the Part I & Part II.	Maximum measured concentration of the analyte in plasma for idarucizumab Time frame: For dose group 1 to 3 (Day 1 to 3-Part-I): predose, 0 (end of infusion), 0.033h, 0.083h, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h. For dose group 4 (Day 1 to 3-Part-I): predose, -0.5h, 0 (end of infusion), 0.033h, 0.083h, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 48h. For dose group 5-7 (Day11 to Day13-Part II): predose, 242h (end of infusion), 242.033h, 242.083h, 242.167h, 242.25h, 242.5h, 242.75h, 243h, 243.5h, 244h, 244.5h, 245h, 246h, 248h, 250h, 252h, 254h, 258h, 266h, 290h.For dose group 8 (day11 to Day13-Part II): predose, 242h (end of infusion), 242.083h, 242.25h, 242.333h, 242.367h, 242.5h, 242.833h, 243.333h, 244h, 245h, 246h, 248h, 252h, 254h, 266h, 290h, 314h.	Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description section	No
Secondary	AUC0-inf for Idarucizumab in the Part I & Part II.	Area under the concentration-time curve of the analyte in plasma for idarucizumab over the time interval from 0 extrapolated to infinity.; Time frame: For dose group 1 to 3 (Day 1 to 3-Part-I): predose, 0 (end of infusion), 0.033h, 0.083, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h. For dose group 4 (Day 1 to 3-Part-I): predose, -0.5h, 0 (end of infusion), 0.033h, 0.083h, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 48h. For dose group 5-7 (Day11 to Day13-Part II): predose, 242h (end of infusion), 242.033h, 242.083h, 242.167h, 242.25h, 242.5h, 242.75h, 243h, 243.5h, 244h, 244.5h, 245h, 246h, 248h, 250h, 252h, 254h, 258h, 266h, 290h.For dose group 8 (day11 to Day13-Part II): predose, 242h (end of infusion), 242.083h, 242.25h, 242.333h, 242.367h, 242.5h, 242.833h, 243.333h, 244h, 245h, 246h, 248h, 252h, 254h, 266h, 290h, 314h.	Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description section	No
Secondary	Ae0-72 for Idarucizumab in the Part I & Part II.	Amount of idarucizumab eliminated in urine over the time interval 0-72. Time frame: For dose groups 1 to 3 (day1 to day4-Part-1):0-4 h, 4-8 h, 8-12 h, 12-24 h, 24-48 h, 48-72 h. For dose groups 5 to 7 (day 11 to day14-Part-II): 0-4 h, 4-8 h, 8-10 h, 10-12 h,12-24 h, 24-48 h, and 48-72 h. For dose groups 8 (day11 to day14-Part-II): 0-4h, 4-8 h, 8-10 h, 10-24 h, 24-48 h, 48-72 h.	Day 1 to 4 (Part I) and Day 11 to 14 (Part II); Time frame are provided in detail in the Description section	No
Secondary	Ae0-73 for the Dose Group 4 in the Part I	Amount of the analyte excreted in urine over the time interval 0-73	For dose group 4 (day1 to day4-Part-1): 0-7h, 7-13h, 13-25h, 25-49h, 49-73h	No
Secondary	AUEC2-12	Area under the effect curve over the time interval from 2 to 12h, AUEC2-12 on Days 4 and 11 for diluted thrombin time (dTT).; For dose groups 5 to 7(day4-Part-II): 74h, 74.5h, 75h, 76h, 78h, 80h, 82h, 84h on day 4. For dose groups 5 to 7(day11-Part-II): 242h, 242.083h, 242.167h, 242.5h, 243h, 244h, 246h, 248h, 250h, 252h. For dose groups 8(day4-Part-II): 74.5 h, 78 h, 84 h on day 4. For dose groups 8(day11-Part-II): 242h, 242.083h,242.25h, 242.333h, 243.333h, 244h, 246h, 248h, 252h on day 11.; AUEC is calculated by multiplying the ratio (Value at each time point/Ebase, unit of Vaue is [s] and Ebase is value [s] at baseline) by time. Therefore, Unit for AUEC2-12 is [h].	Day 4 and Day 11 (Part II); Time frame are provided in detail in the Description section	No

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