- ICH GCP
- US Clinical Trials Registry
- 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
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 Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Antwerpen, Belgium
- 1321.2.1 Boehringer Ingelheim Investigational Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: healthy subjects aged 45-64
Sequential Crossover to Placebo or BI 655075
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Experimental: healthy elderly subjects aged 65-80 year
Sequential Crossover to Placebo or BI 655075
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Experimental: mild renal impairment aged 45-80 years
Sequential Crossover to Placebo or BI 655075
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Experimental: mod renal impairment aged 45-80 years
Sequential Crossover to Placebo or BI 655075
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Reversal of Dabigatran-induced Prolongation of Blood Coagulation Time
Time Frame: End of last infusion and 10 minutes after completion of last infusion of BI 655075
|
Percentage of subjects with at least one assay value from diluted thrombin time (dTT) or ecarin clotting time (ECT) reversed within 10min after completion of infusion.
Reversal was defined as return to baseline, where the threshold for reversal to baseline was determined using PK/PD correlation between unbound sum dabigatran and the clotting parameters ECT and dTT.
Measured at the end of the infusion and 10 min later.
|
End of last infusion and 10 minutes after completion of last infusion of BI 655075
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The Percentage of Subjects With Drug-related Adverse Events
Time Frame: From baseline up to the start of follow-up period (from Day 1 to Day 35)
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The percentage of subjects with possibly drug-related AEs (as defined by the investigator) during the treatment period.
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From baseline up to the start of follow-up period (from Day 1 to Day 35)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
AUC0-infinity (Area Under the Concentration-time Curve of Idarucizumab (Ida) in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
Time Frame: From Day 4 to Day 9 (details in description)
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AUC0-infinity. PK/PD sampling time: (p=predose, D=day)
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From Day 4 to Day 9 (details in description)
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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)
Time Frame: from 2h to12h of post DE dose at steady state (details in description)
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PK/PD sampling time:(d=dose,D=Day,p=predose)
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from 2h to12h of post DE dose at steady state (details in description)
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Aet1-t2, ss (Amount of DE Eliminated in Urine From the Time Point t1 to Time Point t2)
Time Frame: From 0 to 74h post of last DE dose (details in description)
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Urinary excretion of sum dabigatran from the time point t1 to t2 at steady state. PK Urine sampling time: Urine sampling relative to first DE administration: Planned times 72:00 - 73:55h, 73:55 - 80:00h, 80:00 - 86:00h, 86:00 - 98:00h, 98:00 - 122:00h, 122:00 - 146:00h; additional sampling for renal impaired: 146:00 - 170:00; 170:00 - 194:00h. Ae0-26,ss was not measured in Period 3 (re-exposure period). Ae0-74,ss was not measured in healthy subjects aged 45 to 64 years. |
From 0 to 74h post of last DE dose (details in description)
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Cmax (Maximum Measured Concentration of the Ida in Plasma)
Time Frame: From Ida administration to 4 days post dose (details in description)
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Cmax. PK/PD sampling time: (p=predose, D=day)
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From Ida administration to 4 days post dose (details in description)
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Ae0-6 (Amount of Ida Eliminated in Urine From the Time Point 0 to Time Point 6 h)
Time Frame: from 0 to 6 hours of post Ida dose (details in description)
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Ae0-6 (Amount of Ida Eliminated in Urine From the Time Point 0 to Time point 6 h). PK Urine sampling time: Urine sampling relative to DE administration: Planned times 72:00 - 73:55h, 73:55 - 80:00h, 80:00 - 86:00h, 86:00 - 98:00h, 98:00 - 122:00h, 122:00 - 146:00h; additional sampling for renal impaired: 146:00 - 170:00; 170:00 - 194:00h. |
from 0 to 6 hours of post Ida dose (details in description)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1321.2
- 2013-003616-52 (EudraCT Number: EudraCT)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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