Clinical trial NCT01955720: Safety, Tolerability, PK and PD of BI 655075 and Establishment of BI 655075 Dose(s) Effective to Reverse Prolongation of Blood Coagulation Time by Dabigatran
Official title: Randomised, Double-blind, Placebo-controlled, Two-way Cross-over Phase Ib Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 655075 and to Establish the Efficacy of BI 655075 in Reversal of Dabigatran Anticoagulant Activity in Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hemorrhage
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2013-10-07
Enrollment: 46
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To investigate safety, tolerability, PK and PD of BI 655075 and to establish the BI 655075 dose(s) effective to reverse prolongation of blood coagulation time by dabigatran


Eligibility criteria: Inclusion criteria:

* Healthy midage male and female volunteers, age =45 and =64 years, BMI range: =18.5 and =29.9 kg/m2
* Healthy elderly male and female volunteers, age =65 and =80 years, BMI range: =18.5 and = 32 kg/m2
* Male and female volunteers with mild renal impairment (CLcrd 60-90 (mL/min)) in relatively good health, age =45 and =80 years, BMI range: =18.5 and =32 kg/m2 Moderate renal impaired (CLcrd =30 to \<60 mL/min according Cockcroft\&Gault formula in relatively good health, age =45 and =80 years, BMI range: =18.5 and =32 kg/m2

Exclusion criteria:

* Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
* Any evidence of a clinically relevant concomitant disease (other than mild renal impairment in the respective group) A significant disease is defined as a disease which in the opinion of the investigator
* put the volunteer at risk because of participation in the study
* may influence the results of the study
* may influence the volunteer¿s ability to participate in the study
* is not in a stable condition Diabetic, hypercholesterolemia or hypertensive subjects can be entered in this trial if the disease is not significant according to these criteria
* Surgery of the gastrointestinal tract (except appendectomy)
* Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
* History of relevant orthostatic hypotension, fainting spells or blackouts.
* Chronic or relevant acute infections
* History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)

Primary outcomes:
measure: Reversal of Dabigatran-induced Prolongation of Blood Coagulation Time
timeFrame: End of last infusion and 10 minutes after completion of last infusion of BI 655075
measure: The Percentage of Subjects With Drug-related Adverse Events
timeFrame: From baseline up to the start of follow-up period (from Day 1 to Day 35)
Secondary outcomes:
measure: AUC0-infinity (Area Under the Concentration-time Curve of Idarucizumab (Ida) in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
timeFrame: From Day 4 to Day 9 (details in description)
measure: AUC2-12, ss (Area Under the Concentration-time Curve of Unbound Sum Dabigatran (DE) in Plasma at Steady State Over the Time Interval From 2 to 12h)
timeFrame: from 2h to12h of post DE dose at steady state (details in description)
measure: Aet1-t2, ss (Amount of DE Eliminated in Urine From the Time Point t1 to Time Point t2)
timeFrame: From 0 to 74h post of last DE dose (details in description)
measure: Cmax (Maximum Measured Concentration of the Ida in Plasma)
timeFrame: From Ida administration to 4 days post dose (details in description)
measure: Ae0-6 (Amount of Ida Eliminated in Urine From the Time Point 0 to Time Point 6 h)
timeFrame: from 0 to 6 hours of post Ida dose (details in description)
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: 1321.2.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Norris S, Ramael S, Ikushima I, Haazen W, Harada A, Moschetti V, Imazu S, Reilly PA, Lang B, Stangier J, Glund S. Evaluation of the immunogenicity of the dabigatran reversal agent idarucizumab during Phase I studies. Br J Clin Pharmacol. 2017 Aug;83(8):1815-1825. doi: 10.1111/bcp.13269. Epub 2017 Apr 6.
citation: Glund S, Stangier J, van Ryn J, Schmohl M, Moschetti V, Haazen W, De Smet M, Gansser D, Norris S, Lang B, Reilly P, Kreuzer J. Effect of Age and Renal Function on Idarucizumab Pharmacokinetics and Idarucizumab-Mediated Reversal of Dabigatran Anticoagulant Activity in a Randomized, Double-Blind, Crossover Phase Ib Study. Clin Pharmacokinet. 2017 Jan;56(1):41-54. doi: 10.1007/s40262-016-0417-0.
citation: Glund S, Stangier J, van Ryn J, Schmohl M, Moschetti V, Haazen W, De Smet M, Gansser D, Norris S, Lang B, Reilly P, Kreuzer J. Restarting Dabigatran Etexilate 24 h After Reversal With Idarucizumab and Redosing Idarucizumab in Healthy Volunteers. J Am Coll Cardiol. 2016 Apr 5;67(13):1654-1656. doi: 10.1016/j.jacc.2016.01.043. No abstract available.