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Trial record 2 of 4 for:    BI 655075

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01955720
First received: September 30, 2013
Last updated: January 13, 2016
Last verified: January 2016
  Purpose
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

Condition Intervention Phase
Hemorrhage
Drug: BI 655075
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    The percentage of subjects with possibly drug-related AEs (as defined by the investigator) during the treatment period.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    AUC0-infinity. PK/PD sampling time: (p=predose, D=day)

    1. single medium or high dose, healthy subjects(HS) mid-age (45-64 yrs): D4: 8:55p, 9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00; D5: 9:00p, 21:00. D6: 9:00.
    2. single low or high dose, HS elderly or mild renal impaired: D4: 8:55p, 9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00; D5: 9:00; D6: 9:00; D7: 9:00; additional sampling for renal impaired: D8: 9:00;D9: 9:00.
    3. high 2 doses, moderate renal impaired: D4: 8:55p, 9:00, 9:10,9:30,9:55p, 10:00,10:10,10:30,11:00, 13:00, 15:00, 19:00, 21:00, 01:00; D5: 9:00; D6: 9:00; D7: 9:00; additional sampling for renal impaired: D8:9:00; D9:9:00.

  • 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) ] [ Designated as safety issue: No ]

    PK/PD sampling time:(d=dose,D=Day,p=predose)

    1. single medium or high dose,healthy, mid-age (45-64 yrs): D4: 7:00p,8:55p,9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00, 01:00; D5:9:00p,11:00,21:00p; D6:9:00p, 21:00p; D7:9:00p, 11:00.
    2. single low or high dose,healthy elder or mild renal impaired: D4:7:00p,8:55p,9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00;D5:9:00;D6:9:00;D7:9:00; additional sampling for renal impaired: D8:9:00;D9:9:00.
    3. high 2 doses, moderate renal impaired: D4:7:00p,8:55p,9:00,9:10,9:30,9:55p,10:00,10:10,10:30,11:00,13:00,15:00,19:00,21:00,01:00;D5:9:00;D6:9:00; D7:9:00; additional sampling for renal impaired: D8:9:00;D9:9:00.

  • 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) ] [ Designated as safety issue: No ]

    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.


  • Cmax (Maximum Measured Concentration of the Ida in Plasma) [ Time Frame: From Ida administration to 4 days post dose (details in description) ] [ Designated as safety issue: No ]

    Cmax. PK/PD sampling time: (p=predose, D=day)

    1. single medium or high dose, HS mid-age (45-64 yrs): D4: 8:55p, 9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00; D5: 9:00p, 21:00. D6: 9:00.
    2. single low or high dose, healthy elderly or mild RI: D4: 8:55p, 9:00,9:10,9:30,10:00,11:00,13:00,15:00,19:00,21:00,01:00; D5: 9:00; D6: 9:00; D7: 9:00; additional sampling for RI: D8: 9:00;D9: 9:00.
    3. high 2 doses, moderate RI: D4: 8:55p, 9:00, 9:10,9:30,9:55p, 10:00,10:10,10:30,11:00, 13:00, 15:00, 19:00, 21:00, 01:00; D5: 9:00; D6: 9:00; D7: 9:00; additional sampling for RI: D8:9:00; D9:9:00.

  • 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) ] [ Designated as safety issue: No ]

    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.



Enrollment: 46
Study Start Date: September 2013
Study Completion Date: August 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: healthy subjects aged 45-64
Sequential Crossover to Placebo or BI 655075
Drug: BI 655075 Drug: Placebo
Experimental: healthy elderly subjects aged 65-80 year
Sequential Crossover to Placebo or BI 655075
Drug: BI 655075 Drug: Placebo
Experimental: mild renal impairment aged 45-80 years
Sequential Crossover to Placebo or BI 655075
Drug: BI 655075 Drug: Placebo
Experimental: mod renal impairment aged 45-80 years
Sequential Crossover to Placebo or BI 655075
Drug: Placebo Drug: BI 655075

  Eligibility

Ages Eligible for Study:   45 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01955720

Locations
Belgium
1321.2.1 Boehringer Ingelheim Investigational Site
Antwerpen, Belgium
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01955720     History of Changes
Other Study ID Numbers: 1321.2  2013-003616-52 
Study First Received: September 30, 2013
Results First Received: November 13, 2015
Last Updated: January 13, 2016
Health Authority: Belgium: Federal Agency for Medicinal and Health Products

Additional relevant MeSH terms:
Hemorrhage
Pathologic Processes
Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants

ClinicalTrials.gov processed this record on December 02, 2016