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Trial record 90 of 333 for:    DABIGATRAN

Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BI 655075 (Idarucizumab) Administered Alone or With Dabigatran Etexilate in Japanese Healthy Subjects

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ClinicalTrials.gov Identifier: NCT02028780
Recruitment Status : Completed
First Posted : January 7, 2014
Results First Posted : February 11, 2016
Last Update Posted : February 11, 2016
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: Placebo to dose
Drug: Idarucizumab
Drug: Placebo to Idarucizumab
Drug: dabigatran
Enrollment 80
Recruitment Details  
Pre-assignment Details Randomised, double-blind within dose groups, placebo controlled, sequential rising order, single centre trial. This study has two phases ie., Observation phase (Single administration of placebo or BI study drug and 6-14 days follow up) and Follow up phase (End of observation phase to 92-98 days after administration of Placebo or BI study drug).
Arm/Group Title Placebo_5m (Part I) Placebo_1h (Part I) BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) BI8000mg_1h (Dose group4 - Part I) DE+Placebo_5m (Part II) DE+Placebo+Placebo (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Hide Arm/Group Description Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1. Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1. Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1. Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1. Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1. Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1. Subject received a multiple oral doses of dabigatran etexilate 220 mg twice daily(b.i.d.) from Days 1 to 3 and once daily(q.d)on Day 4 and from Days 8 to 10 and once daily(q.d)on Day 11,followed with a single intravenous infusion of matching placebo to idarucizumab for 5min, approximately 2h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d. from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of two doses of matching placebo to Idarucizumab for 5 min + 5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Period Title: Observation Phase
Started 6 2 6 6 6 6 9 3 9 9 9 9
Completed 6 2 6 6 6 6 9 3 9 9 9 9
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Follow up Phase
Started 6 2 6 6 6 6 9 3 9 9 9 9
Completed 6 2 6 6 6 6 9 3 9 9 9 9
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0
Arm/Group Title Placebo_5m (Part I) Placebo_1h (Part I) BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) BI8000mg_1h (Dose group4 - Part I) DE+Placebo_5m (Part II) DE+Placebo+Placebo (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II) Total
Hide Arm/Group Description Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1. Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1. Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1. Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1. Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1. Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1. Subject received a multiple oral doses of dabigatran etexilate 220 mg twice daily(b.i.d.) from Days 1 to 3 and once daily(q.d)on Day 4 and from Days 8 to 10 and once daily(q.d)on Day 11,followed with a single intravenous infusion of matching placebo to idarucizumab for 5min, approximately 2h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d. from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of two doses of matching placebo to Idarucizumab for 5 min + 5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Total of all reporting groups
Overall Number of Baseline Participants 6 2 6 6 6 6 9 3 9 9 9 9 80
Hide Baseline Analysis Population Description
Treated Set (TS): : This subject set included all subjects who received the idarucizumab or placebo.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 2 participants 6 participants 6 participants 6 participants 6 participants 9 participants 3 participants 9 participants 9 participants 9 participants 9 participants 80 participants
28.7  (10.5) 32.5  (4.9) 31.5  (10.9) 27.8  (7.7) 31.5  (8.3) 32.2  (8.1) 24.7  (3.3) 29.7  (5.0) 23.8  (3.1) 25.7  (3.1) 25.4  (2.7) 24.4  (1.4) 27.3  (6.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 2 participants 6 participants 6 participants 6 participants 6 participants 9 participants 3 participants 9 participants 9 participants 9 participants 9 participants 80 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
6
 100.0%
2
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
9
 100.0%
3
 100.0%
9
 100.0%
9
 100.0%
9
 100.0%
9
 100.0%
80
 100.0%
1.Primary Outcome
Title Percentage of Subjects With Drug-related Adverse Events in Part 1 and Part 2
Hide Description Percentage of subjects with drug-related adverse events in Part 1 and Part 2.
Time Frame From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
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Treated set (TS)
Arm/Group Title Placebo_5m (Part I) Placebo_1h (Part I) BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) BI8000mg_1h (Dose group4 - Part I) DE+Placebo_5m (Part II) DE+Placebo+Placebo (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Hide Arm/Group Description:
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
Subject received a multiple oral doses of dabigatran etexilate 220 mg twice daily(b.i.d.) from Days 1 to 3 and once daily(q.d)on Day 4 and from Days 8 to 10 and once daily(q.d)on Day 11,followed with a single intravenous infusion of matching placebo to idarucizumab for 5min, approximately 2h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d. from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of two doses of matching placebo to Idarucizumab for 5 min + 5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Overall Number of Participants Analyzed 6 2 6 6 6 6 9 3 9 9 9 9
Measure Type: Number
Unit of Measure: Percentage of participants
16.7 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0
2.Secondary Outcome
Title Ae0−74,ss on Days 4 and 11 for Sum Dabigatran (Part II)
Hide Description Amount of analyte eliminated in urine at steady state from the time point 0 hours to time point 74 hours.
Time Frame 0–2 h, 2–6 h, 6–10 h, 10–12 h,12–14h, 14-26 h, 26-50 h, 50-74 h after drug administration of dabigatran etexilate on Day 4 and Day 11.
Hide Outcome Measure Data
Hide Analysis Population Description
PKS set: This subject set included all subjects who received the idarucizumab and who had at least one pharmacokinetic parameter. For the Part 2, subjects who had the emesis with onset at or before twice the median tmax of dabigatran were not included in this set.
Arm/Group Title DE+Placebo_5m (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Hide Arm/Group Description:
Subject received a multiple oral doses of dabigatran etexilate 220 mg twice daily(b.i.d.) from Days 1 to 3 and once daily(q.d)on Day 4 and from Days 8 to 10 and once daily(q.d)on Day 11,followed with a single intravenous infusion of matching placebo to idarucizumab for 5min, approximately 2h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Overall Number of Participants Analyzed 12 9 9 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg
Day 4
9250
(42.0%)
12800
(21.6%)
11700
(45.7%)
8810
(33.8%)
11000
(32.9%)
Day 11
9690
(27.7%)
12500
(32.0%)
13100
(30.1%)
9310
(41.0%)
10600
(28.1%)
3.Secondary Outcome
Title AUC2-12,ss on Days 4 and 11 for Unbound Sum Dabigatran (Part II).
Hide Description

Area under the concentration-time curve of the dabigatran in plasma at steady state over the time interval 2 hours-12 hours.

Time Frame: For dose group 5 to 7 (Day 1 to 3-Part-I):74hours (h), 74.5h, 75h, 76h, 78h, 80h, 82h, 84h, For dose group 8 (Day 1 to 3-Part-I): 74h, 74.5h, 75h, 76h, 78h, 80h, 82h, 84h and For dose group 5-7 (Day11 to Day13-Part II):242h, 242.167h, 242.5h, 243h, 244h,246h, 248h, 250h, 252h. For dose group 8 (Day11 to Day13-Part II):242h, 242.083h, 242.25h, 242.333h, 243.333h, 244h, 246h, 248h, 252h.

Time Frame Day 4 (Part I) and Day 11 (Part II). Time frame are provided in detail in the Description section
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PKS set
Arm/Group Title DE+Placebo_5m (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Hide Arm/Group Description:
Subject received a multiple oral doses of dabigatran etexilate 220 mg twice daily(b.i.d.) from Days 1 to 3 and once daily(q.d)on Day 4 and from Days 8 to 10 and once daily(q.d)on Day 11,followed with a single intravenous infusion of matching placebo to idarucizumab for 5min, approximately 2h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Overall Number of Participants Analyzed 12 9 9 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Day 4
909
(56.2%)
1260
(25.0%)
1010
(54.1%)
802
(46.8%)
1100
(25.6%)
Day 11
909
(34.8%)
330
(109%)
82.2
(149%)
10.1
(1.86%)
10.0
(0.0213%)
4.Secondary Outcome
Title Cmax for Idarucizumab in the Part I & Part II.
Hide Description Maximum measured concentration of the analyte in plasma for idarucizumab Time frame: For dose group 1 to 3 (Day 1 to 3-Part-I): predose, 0 (end of infusion), 0.033h, 0.083h, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h. For dose group 4 (Day 1 to 3-Part-I): predose, −0.5h, 0 (end of infusion), 0.033h, 0.083h, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 48h. For dose group 5-7 (Day11 to Day13-Part II): predose, 242h (end of infusion), 242.033h, 242.083h, 242.167h, 242.25h, 242.5h, 242.75h, 243h, 243.5h, 244h, 244.5h, 245h, 246h, 248h, 250h, 252h, 254h, 258h, 266h, 290h.For dose group 8 (day11 to Day13-Part II): predose, 242h (end of infusion), 242.083h, 242.25h, 242.333h, 242.367h, 242.5h, 242.833h, 243.333h, 244h, 245h, 246h, 248h, 252h, 254h, 266h, 290h, 314h.
Time Frame Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description section
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PKS set
Arm/Group Title BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) BI8000mg_1h (Dose group4 - Part I) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Hide Arm/Group Description:
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Overall Number of Participants Analyzed 6 6 6 6 9 9 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
6810
(10.1%)
15700
(10.9%)
28100
(14.3%)
37600
(6.88%)
9510
(33.8%)
17600
(16.8%)
30200
(17.7%)
30100
(11.5%)
5.Secondary Outcome
Title AUC0-inf for Idarucizumab in the Part I & Part II.
Hide Description

Area under the concentration-time curve of the analyte in plasma for idarucizumab over the time interval from 0 extrapolated to infinity.

Time frame: For dose group 1 to 3 (Day 1 to 3-Part-I): predose, 0 (end of infusion), 0.033h, 0.083, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h. For dose group 4 (Day 1 to 3-Part-I): predose, −0.5h, 0 (end of infusion), 0.033h, 0.083h, 0.167h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 16h, 24h, 48h. For dose group 5-7 (Day11 to Day13-Part II): predose, 242h (end of infusion), 242.033h, 242.083h, 242.167h, 242.25h, 242.5h, 242.75h, 243h, 243.5h, 244h, 244.5h, 245h, 246h, 248h, 250h, 252h, 254h, 258h, 266h, 290h.For dose group 8 (day11 to Day13-Part II): predose, 242h (end of infusion), 242.083h, 242.25h, 242.333h, 242.367h, 242.5h, 242.833h, 243.333h, 244h, 245h, 246h, 248h, 252h, 254h, 266h, 290h, 314h.

Time Frame Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description section
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PKS set
Arm/Group Title BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) BI8000mg_1h (Dose group4 - Part I) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Hide Arm/Group Description:
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Overall Number of Participants Analyzed 6 6 6 6 9 9 8 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
9150
(15.0%)
19500
(17.8%)
37600
(14.4%)
76800
(14.8%)
8590
(14.2%)
19200
(18.5%)
34500
(16.6%)
43300
(8.25%)
6.Secondary Outcome
Title Ae0-72 for Idarucizumab in the Part I & Part II.
Hide Description Amount of idarucizumab eliminated in urine over the time interval 0-72. Time frame: For dose groups 1 to 3 (day1 to day4-Part-1):0–4 h, 4–8 h, 8–12 h, 12–24 h, 24–48 h, 48–72 h. For dose groups 5 to 7 (day 11 to day14-Part-II): 0-4 h, 4–8 h, 8–10 h, 10–12 h,12–24 h, 24–48 h, and 48–72 h. For dose groups 8 (day11 to day14-Part-II): 0-4h, 4–8 h, 8–10 h, 10–24 h, 24–48 h, 48–72 h.
Time Frame Day 1 to 4 (Part I) and Day 11 to 14 (Part II); Time frame are provided in detail in the Description section
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PKS set. Ae 0-72 data is not available for BI8000mg_1h (Dose group 4 - Part I) due to longer infusion time resulting different urine collection interval. Instead, Ae 0-73 is presented for BI8000mg_1h as separate endpoint.
Arm/Group Title BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
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Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Overall Number of Participants Analyzed 6 6 6 9 9 9 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μmol
1.54
(54.9%)
6.10
(165%)
20.5
(52.4%)
4.21
(35.1%)
13.8
(12.5%)
42.6
(16.4%)
51.5
(18.1%)
7.Secondary Outcome
Title Ae0-73 for the Dose Group 4 in the Part I
Hide Description Amount of the analyte excreted in urine over the time interval 0-73
Time Frame For dose group 4 (day1 to day4-Part-1): 0-7h, 7-13h, 13-25h, 25-49h, 49-73h
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PKS set. The results from dose group 4 has been disclosed, because only dose group 4 had 1hr infusion, Ae 0-73 was reported, instead of Ae0-72.
Arm/Group Title BI8000mg_1h (Dose group4 - Part I)
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Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
Overall Number of Participants Analyzed 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μmol
69.1
(25.0%)
8.Secondary Outcome
Title AUEC2-12
Hide Description

Area under the effect curve over the time interval from 2 to 12h, AUEC2-12 on Days 4 and 11 for diluted thrombin time (dTT).

For dose groups 5 to 7(day4-Part-II): 74h, 74.5h, 75h, 76h, 78h, 80h, 82h, 84h on day 4. For dose groups 5 to 7(day11-Part-II): 242h, 242.083h, 242.167h, 242.5h, 243h, 244h, 246h, 248h, 250h, 252h. For dose groups 8(day4-Part-II): 74.5 h, 78 h, 84 h on day 4. For dose groups 8(day11-Part-II): 242h, 242.083h,242.25h, 242.333h, 243.333h, 244h, 246h, 248h, 252h on day 11.

AUEC is calculated by multiplying the ratio (Value at each time point/Ebase, unit of Vaue is [s] and Ebase is value [s] at baseline) by time. Therefore, Unit for AUEC2-12 is [h].

Time Frame Day 4 and Day 11 (Part II); Time frame are provided in detail in the Description section
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Pharmacodynamic set (PDS): The PDS comprised all subjects in the TS who provided at least 1 evaluable predose and 1 on-treatment pharmacodynamic observation.
Arm/Group Title DE+Placebo_5m (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
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Subject received a multiple oral doses of dabigatran etexilate 220 mg twice daily(b.i.d.) from Days 1 to 3 and once daily(q.d)on Day 4 and from Days 8 to 10 and once daily(q.d)on Day 11,followed with a single intravenous infusion of matching placebo to idarucizumab for 5min, approximately 2h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
Overall Number of Participants Analyzed 12 9 9 9 9
Mean (Standard Deviation)
Unit of Measure: h
Day 4 16.3  (2.30) 18.0  (1.79) 17.4  (4.00) 15.5  (2.17) 17.3  (2.02)
Day 11 15.8  (1.93) 12.5  (1.74) 11.2  (2.23) 9.95  (0.206) 10.0  (0.131)
Time Frame From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo_5m (Part I) Placebo_1h (Part I) BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) BI8000mg_1h (Dose group4 - Part I) DE+Placebo_5m (Part II) DE+Placebo+Placebo (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Hide Arm/Group Description Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1. Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1. Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1. Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1. Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1. Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1. Subject received a multiple oral doses of dabigatran etexilate 220 mg twice daily(b.i.d.) from Days 1 to 3 and once daily(q.d)on Day 4 and from Days 8 to 10 and once daily(q.d)on Day 11,followed with a single intravenous infusion of matching placebo to idarucizumab for 5min, approximately 2h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d. from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of two doses of matching placebo to Idarucizumab for 5 min + 5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 1000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 2000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with a single intravenously infusion of Idarucizumab 4000 mg for 5 min, approximately 2 h after the last dose of dabigatran etexilate on Day 11. Subject received multiple oral doses of dabigatran etexilate 220 mg b.i.d.from Days 1 to 3 and q.d on Day 4 and from Days 8 to 10 and q.d on Day 11, followed with intravenously infusion of two doses of Idarucizumab 2500mg+2500mg for 5 min+5 min, with a 15 min infusion interval between two doses, approximately 2 h after the last dose of dabigatran etexilate on Day 11.
All-Cause Mortality
Placebo_5m (Part I) Placebo_1h (Part I) BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) BI8000mg_1h (Dose group4 - Part I) DE+Placebo_5m (Part II) DE+Placebo+Placebo (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo_5m (Part I) Placebo_1h (Part I) BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) BI8000mg_1h (Dose group4 - Part I) DE+Placebo_5m (Part II) DE+Placebo+Placebo (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/2 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/9 (0.00%)   0/3 (0.00%)   0/9 (0.00%)   0/9 (0.00%)   0/9 (0.00%)   0/9 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo_5m (Part I) Placebo_1h (Part I) BI1000mg_5m (Dose group1 - Part I) BI2000mg_5m (Dose group2 - Part I) BI4000mg_5m (Dose group3 - Part I) BI8000mg_1h (Dose group4 - Part I) DE+Placebo_5m (Part II) DE+Placebo+Placebo (Part II) DE+1000mg_5m (Dose group5 - Part II) DE+2000mg_5m (Dose group6 - Part II) DE+4000mg_5m (Dose group7 - Part II) DE+2500mg+2500mg (Dose group8 - Part II)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/6 (16.67%)   0/2 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/9 (0.00%)   0/3 (0.00%)   0/9 (0.00%)   0/9 (0.00%)   0/9 (0.00%)   0/9 (0.00%) 
Investigations                         
Blood creatine phosphokinase increased  1  1/6 (16.67%)  0/2 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/3 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%)  0/9 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
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Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02028780     History of Changes
Other Study ID Numbers: 1321.5
First Submitted: January 6, 2014
First Posted: January 7, 2014
Results First Submitted: November 13, 2015
Results First Posted: February 11, 2016
Last Update Posted: February 11, 2016