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

Phase 1CompletedNCT01955720

Boehringer Ingelheim46 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Hemorrhage

Interventions

BI 655075DRUG

PlaceboDRUG

BI 655075DRUG

Eligibility

Sex: ALLMin age: 45 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (1)

1321.2.1 Boehringer Ingelheim Investigational Site

Antwerp, Belgium

Outcomes

Primary Outcomes

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.

Time frame: 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.

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

Secondary Outcomes

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

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.

Time frame: 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)

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.

Data from ClinicalTrials.gov

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