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Completed

NCT Number: 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

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

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Key information

Conditions

Hemorrhage Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

45 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

1321.2.1 Boehringer Ingelheim Investigational Site

Antwerp, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

BI 655075

Drug

Placebo

Drug

Primary outcomes

  1. 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.

  2. 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)

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

Secondary outcomes

  1. 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)

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

    • 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.
    • 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.
    • 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.

  2. 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)

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

    • 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.
    • 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.
    • 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.

  3. 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)

    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.

  4. Cmax (Maximum Measured Concentration of the Ida in Plasma)

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

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

    • 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.
    • 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.
    • 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.

  5. 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)

    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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Oct 7, 2013
Registry last updated
Feb 11, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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