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
- Conditions
- Hemorrhage
- Interventions
- Drug: BI 655075Drug: Placebo
- Registration Number
- NCT01955720
- Lead Sponsor
- Boehringer Ingelheim
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description mild renal impairment aged 45-80 years Placebo Sequential Crossover to Placebo or BI 655075 healthy elderly subjects aged 65-80 year Placebo Sequential Crossover to Placebo or BI 655075 healthy elderly subjects aged 65-80 year BI 655075 Sequential Crossover to Placebo or BI 655075 healthy subjects aged 45-64 Placebo Sequential Crossover to Placebo or BI 655075 mild renal impairment aged 45-80 years BI 655075 Sequential Crossover to Placebo or BI 655075 healthy subjects aged 45-64 BI 655075 Sequential Crossover to Placebo or BI 655075 mod renal impairment aged 45-80 years Placebo Sequential Crossover to Placebo or BI 655075 mod renal impairment aged 45-80 years BI 655075 Sequential Crossover to Placebo or BI 655075
- Primary Outcome Measures
Name Time Method The Percentage of Subjects With Drug-related Adverse Events 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.
Reversal of Dabigatran-induced Prolongation of Blood Coagulation Time 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.
- Secondary Outcome Measures
Name Time Method 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) 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.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) 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.Cmax (Maximum Measured Concentration of the Ida in Plasma) From Ida administration to 4 days post dose (details in description) 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.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) 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) 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.
Trial Locations
- Locations (1)
1321.2.1 Boehringer Ingelheim Investigational Site
🇧🇪Antwerpen, Belgium