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

NCT01955720 | Completed Phase 1 Results

• 2 other identifiers: 1321.22013-003616-52
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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

Conditions

Hemorrhage

Outcome Measures

Primary Outcomes (2)

• Reversal of Dabigatran-induced Prolongation of Blood Coagulation Time

  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

• The Percentage of Subjects With Drug-related Adverse Events

  The percentage of subjects with possibly drug-related AEs (as defined by the investigator) during the treatment period.

  From baseline up to the start of follow-up period (from Day 1 to Day 35)

Secondary Outcomes (5)

• AUC0-infinity (Area Under the Concentration-time Curve of Idarucizumab (Ida) in Plasma Over the Time Interval From 0 Extrapolated to Infinity)

  From Day 4 to Day 9 (details in description)

• 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)

  from 2h to12h of post DE dose at steady state (details in description)

• Aet1-t2, ss (Amount of DE Eliminated in Urine From the Time Point t1 to Time Point t2)

  From 0 to 74h post of last DE dose (details in description)

• Cmax (Maximum Measured Concentration of the Ida in Plasma)

  From Ida administration to 4 days post dose (details in description)

• Ae0-6 (Amount of Ida Eliminated in Urine From the Time Point 0 to Time Point 6 h)

  from 0 to 6 hours of post Ida dose (details in description)

Study Arms (4)

healthy subjects aged 45-64

EXPERIMENTAL

Sequential Crossover to Placebo or BI 655075

Drug: BI 655075; Drug: Placebo

healthy elderly subjects aged 65-80 year

EXPERIMENTAL

Sequential Crossover to Placebo or BI 655075

Drug: BI 655075; Drug: Placebo

mild renal impairment aged 45-80 years

EXPERIMENTAL

Sequential Crossover to Placebo or BI 655075

Drug: BI 655075; Drug: Placebo

mod renal impairment aged 45-80 years

EXPERIMENTAL

Sequential Crossover to Placebo or BI 655075

Drug: Placebo; Drug: BI 655075

Interventions

BI 655075 DRUG

mild renal impairment aged 45-80 years

Placebo DRUG

mod renal impairment aged 45-80 years

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

1321.2.1 Boehringer Ingelheim Investigational Site

Antwerp, Belgium

Location

Related Publications (3)

• 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.

  PMID: 28230262 DERIVED

• 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.

  PMID: 27317414 DERIVED

• 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.

  PMID: 27150693 DERIVED

MeSH Terms

Conditions

Hemorrhage

Interventions

idarucizumab

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2013
• First Posted: October 7, 2013
• Study Start: September 1, 2013
• Primary Completion: May 1, 2014
• Study Completion: August 1, 2014
• Last Updated: February 11, 2016
• Results First Posted: February 11, 2016

Record last verified: 2016-01

Locations

BE (1)