Trial Outcomes & Findings for Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BI 655075 (Idarucizumab) Administered Alone or With Dabigatran Etexilate in Japanese Healthy Subjects (NCT NCT02028780)
NCT ID: NCT02028780
Last Updated: 2016-02-11
Results Overview
Percentage of subjects with drug-related adverse events in Part 1 and Part 2.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
80 participants
Primary outcome timeframe
From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
Results posted on
2016-02-11
Participant Flow
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).
Participant milestones
| Measure |
Placebo_5m (Part I)
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
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.
|
DE+Placebo+Placebo (Part II)
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.
|
DE+1000mg_5m (Dose group5 - Part II)
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.
|
DE+2000mg_5m (Dose group6 - Part II)
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.
|
DE+4000mg_5m (Dose group7 - Part II)
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Observation Phase
STARTED
|
6
|
2
|
6
|
6
|
6
|
6
|
9
|
3
|
9
|
9
|
9
|
9
|
|
Observation Phase
COMPLETED
|
6
|
2
|
6
|
6
|
6
|
6
|
9
|
3
|
9
|
9
|
9
|
9
|
|
Observation Phase
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Follow up Phase
STARTED
|
6
|
2
|
6
|
6
|
6
|
6
|
9
|
3
|
9
|
9
|
9
|
9
|
|
Follow up Phase
COMPLETED
|
6
|
2
|
6
|
6
|
6
|
6
|
9
|
3
|
9
|
9
|
9
|
9
|
|
Follow up Phase
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BI 655075 (Idarucizumab) Administered Alone or With Dabigatran Etexilate in Japanese Healthy Subjects
Baseline characteristics by cohort
| Measure |
Placebo_5m (Part I)
n=6 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
n=2 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
n=9 Participants
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.
|
DE+Placebo+Placebo (Part II)
n=3 Participants
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.
|
DE+1000mg_5m (Dose group5 - Part II)
n=9 Participants
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.
|
DE+2000mg_5m (Dose group6 - Part II)
n=9 Participants
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.
|
DE+4000mg_5m (Dose group7 - Part II)
n=9 Participants
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
n=9 Participants
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
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
28.7 Years
STANDARD_DEVIATION 10.5 • n=5 Participants
|
32.5 Years
STANDARD_DEVIATION 4.9 • n=7 Participants
|
31.5 Years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
27.8 Years
STANDARD_DEVIATION 7.7 • n=4 Participants
|
31.5 Years
STANDARD_DEVIATION 8.3 • n=21 Participants
|
32.2 Years
STANDARD_DEVIATION 8.1 • n=10 Participants
|
24.7 Years
STANDARD_DEVIATION 3.3 • n=115 Participants
|
29.7 Years
STANDARD_DEVIATION 5.0 • n=24 Participants
|
23.8 Years
STANDARD_DEVIATION 3.1 • n=42 Participants
|
25.7 Years
STANDARD_DEVIATION 3.1 • n=42 Participants
|
25.4 Years
STANDARD_DEVIATION 2.7 • n=42 Participants
|
24.4 Years
STANDARD_DEVIATION 1.4 • n=42 Participants
|
27.3 Years
STANDARD_DEVIATION 6.4 • n=36 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
3 Participants
n=24 Participants
|
9 Participants
n=42 Participants
|
9 Participants
n=42 Participants
|
9 Participants
n=42 Participants
|
9 Participants
n=42 Participants
|
80 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)Population: Treated set (TS)
Percentage of subjects with drug-related adverse events in Part 1 and Part 2.
Outcome measures
| Measure |
Placebo_5m (Part I)
n=6 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
n=2 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
n=9 Participants
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.
|
DE+Placebo+Placebo (Part II)
n=3 Participants
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.
|
DE+1000mg_5m (Dose group5 - Part II)
n=9 Participants
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.
|
DE+2000mg_5m (Dose group6 - Part II)
n=9 Participants
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.
|
DE+4000mg_5m (Dose group7 - Part II)
n=9 Participants
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
n=9 Participants
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Subjects With Drug-related Adverse Events in Part 1 and Part 2
|
16.7 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Amount of analyte eliminated in urine at steady state from the time point 0 hours to time point 74 hours.
Outcome measures
| Measure |
Placebo_5m (Part I)
n=12 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
n=9 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
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.
|
DE+Placebo+Placebo (Part II)
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.
|
DE+1000mg_5m (Dose group5 - Part II)
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.
|
DE+2000mg_5m (Dose group6 - Part II)
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.
|
DE+4000mg_5m (Dose group7 - Part II)
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ae0-74,ss on Days 4 and 11 for Sum Dabigatran (Part II)
Day 4
|
9250 μg
Geometric Coefficient of Variation 42.0
|
12800 μg
Geometric Coefficient of Variation 21.6
|
11700 μg
Geometric Coefficient of Variation 45.7
|
8810 μg
Geometric Coefficient of Variation 33.8
|
11000 μg
Geometric Coefficient of Variation 32.9
|
—
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—
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—
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—
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—
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—
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—
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Ae0-74,ss on Days 4 and 11 for Sum Dabigatran (Part II)
Day 11
|
9690 μg
Geometric Coefficient of Variation 27.7
|
12500 μg
Geometric Coefficient of Variation 32.0
|
13100 μg
Geometric Coefficient of Variation 30.1
|
9310 μg
Geometric Coefficient of Variation 41.0
|
10600 μg
Geometric Coefficient of Variation 28.1
|
—
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—
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—
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SECONDARY outcome
Timeframe: Day 4 (Part I) and Day 11 (Part II). Time frame are provided in detail in the Description sectionPopulation: PKS set
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.
Outcome measures
| Measure |
Placebo_5m (Part I)
n=12 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
n=9 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
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.
|
DE+Placebo+Placebo (Part II)
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.
|
DE+1000mg_5m (Dose group5 - Part II)
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.
|
DE+2000mg_5m (Dose group6 - Part II)
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.
|
DE+4000mg_5m (Dose group7 - Part II)
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC2-12,ss on Days 4 and 11 for Unbound Sum Dabigatran (Part II).
Day 4
|
909 ng*h/mL
Geometric Coefficient of Variation 56.2
|
1260 ng*h/mL
Geometric Coefficient of Variation 25.0
|
1010 ng*h/mL
Geometric Coefficient of Variation 54.1
|
802 ng*h/mL
Geometric Coefficient of Variation 46.8
|
1100 ng*h/mL
Geometric Coefficient of Variation 25.6
|
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—
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AUC2-12,ss on Days 4 and 11 for Unbound Sum Dabigatran (Part II).
Day 11
|
909 ng*h/mL
Geometric Coefficient of Variation 34.8
|
330 ng*h/mL
Geometric Coefficient of Variation 109
|
82.2 ng*h/mL
Geometric Coefficient of Variation 149
|
10.1 ng*h/mL
Geometric Coefficient of Variation 1.86
|
10.0 ng*h/mL
Geometric Coefficient of Variation 0.0213
|
—
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—
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—
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description sectionPopulation: PKS set
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.
Outcome measures
| Measure |
Placebo_5m (Part I)
n=6 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
n=6 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
n=9 Participants
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.
|
DE+Placebo+Placebo (Part II)
n=9 Participants
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.
|
DE+1000mg_5m (Dose group5 - Part II)
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.
|
DE+2000mg_5m (Dose group6 - Part II)
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.
|
DE+4000mg_5m (Dose group7 - Part II)
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Cmax for Idarucizumab in the Part I & Part II.
|
6810 nmol/L
Geometric Coefficient of Variation 10.1
|
15700 nmol/L
Geometric Coefficient of Variation 10.9
|
28100 nmol/L
Geometric Coefficient of Variation 14.3
|
37600 nmol/L
Geometric Coefficient of Variation 6.88
|
9510 nmol/L
Geometric Coefficient of Variation 33.8
|
17600 nmol/L
Geometric Coefficient of Variation 16.8
|
30200 nmol/L
Geometric Coefficient of Variation 17.7
|
30100 nmol/L
Geometric Coefficient of Variation 11.5
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to 3 (Part I) and Day 11 to 13 (Part II); Time frame are provided in detail in the Description sectionPopulation: PKS set
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.
Outcome measures
| Measure |
Placebo_5m (Part I)
n=6 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
n=6 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
n=8 Participants
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.
|
DE+Placebo+Placebo (Part II)
n=9 Participants
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.
|
DE+1000mg_5m (Dose group5 - Part II)
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.
|
DE+2000mg_5m (Dose group6 - Part II)
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.
|
DE+4000mg_5m (Dose group7 - Part II)
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUC0-inf for Idarucizumab in the Part I & Part II.
|
9150 nmol*h/L
Geometric Coefficient of Variation 15.0
|
19500 nmol*h/L
Geometric Coefficient of Variation 17.8
|
37600 nmol*h/L
Geometric Coefficient of Variation 14.4
|
76800 nmol*h/L
Geometric Coefficient of Variation 14.8
|
8590 nmol*h/L
Geometric Coefficient of Variation 14.2
|
19200 nmol*h/L
Geometric Coefficient of Variation 18.5
|
34500 nmol*h/L
Geometric Coefficient of Variation 16.6
|
43300 nmol*h/L
Geometric Coefficient of Variation 8.25
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to 4 (Part I) and Day 11 to 14 (Part II); Time frame are provided in detail in the Description sectionPopulation: 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.
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.
Outcome measures
| Measure |
Placebo_5m (Part I)
n=6 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
n=6 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
n=6 Participants
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
n=9 Participants
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.
|
DE+Placebo+Placebo (Part II)
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.
|
DE+1000mg_5m (Dose group5 - Part II)
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.
|
DE+2000mg_5m (Dose group6 - Part II)
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.
|
DE+4000mg_5m (Dose group7 - Part II)
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ae0-72 for Idarucizumab in the Part I & Part II.
|
1.54 μmol
Geometric Coefficient of Variation 54.9
|
6.10 μmol
Geometric Coefficient of Variation 165
|
20.5 μmol
Geometric Coefficient of Variation 52.4
|
4.21 μmol
Geometric Coefficient of Variation 35.1
|
13.8 μmol
Geometric Coefficient of Variation 12.5
|
42.6 μmol
Geometric Coefficient of Variation 16.4
|
51.5 μmol
Geometric Coefficient of Variation 18.1
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: For dose group 4 (day1 to day4-Part-1): 0-7h, 7-13h, 13-25h, 25-49h, 49-73hPopulation: 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.
Amount of the analyte excreted in urine over the time interval 0-73
Outcome measures
| Measure |
Placebo_5m (Part I)
n=6 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
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.
|
DE+Placebo+Placebo (Part II)
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.
|
DE+1000mg_5m (Dose group5 - Part II)
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.
|
DE+2000mg_5m (Dose group6 - Part II)
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.
|
DE+4000mg_5m (Dose group7 - Part II)
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ae0-73 for the Dose Group 4 in the Part I
|
69.1 μmol
Geometric Coefficient of Variation 25.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 4 and Day 11 (Part II); Time frame are provided in detail in the Description sectionPopulation: Pharmacodynamic set (PDS): The PDS comprised all subjects in the TS who provided at least 1 evaluable predose and 1 on-treatment pharmacodynamic observation.
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 \[h\].
Outcome measures
| Measure |
Placebo_5m (Part I)
n=12 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
n=9 Participants
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
n=9 Participants
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
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.
|
DE+Placebo+Placebo (Part II)
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.
|
DE+1000mg_5m (Dose group5 - Part II)
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.
|
DE+2000mg_5m (Dose group6 - Part II)
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.
|
DE+4000mg_5m (Dose group7 - Part II)
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
AUEC2-12
Day 4
|
16.3 h
Standard Deviation 2.30
|
18.0 h
Standard Deviation 1.79
|
17.4 h
Standard Deviation 4.00
|
15.5 h
Standard Deviation 2.17
|
17.3 h
Standard Deviation 2.02
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
AUEC2-12
Day 11
|
15.8 h
Standard Deviation 1.93
|
12.5 h
Standard Deviation 1.74
|
11.2 h
Standard Deviation 2.23
|
9.95 h
Standard Deviation 0.206
|
10.0 h
Standard Deviation 0.131
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Placebo_5m (Part I)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo_1h (Part I)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
BI1000mg_5m (Dose group1 - Part I)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
BI2000mg_5m (Dose group2 - Part I)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
BI4000mg_5m (Dose group3 - Part I)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
BI8000mg_1h (Dose group4 - Part I)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
DE+Placebo_5m (Part II)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
DE+Placebo+Placebo (Part II)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
DE+1000mg_5m (Dose group5 - Part II)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
DE+2000mg_5m (Dose group6 - Part II)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
DE+4000mg_5m (Dose group7 - Part II)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
DE+2500mg+2500mg (Dose group8 - Part II)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo_5m (Part I)
n=6 participants at risk
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 5min on Day 1.
|
Placebo_1h (Part I)
n=2 participants at risk
Subject received a single intravenous infusion of matching placebo to idarucizumab once daily for 1h (hour) on Day 1.
|
BI1000mg_5m (Dose group1 - Part I)
n=6 participants at risk
Subject received a single intravenous infusion of idarucizumab 1000mg for 5min on Day 1.
|
BI2000mg_5m (Dose group2 - Part I)
n=6 participants at risk
Subject received a single intravenous infusion of idarucizumab 2000mg for 5min on Day 1.
|
BI4000mg_5m (Dose group3 - Part I)
n=6 participants at risk
Subject received a single intravenous infusion of idarucizumab 4000mg for 5min on Day 1.
|
BI8000mg_1h (Dose group4 - Part I)
n=6 participants at risk
Subject received a single intravenous infusion of idarucizumab 8000mg for 1h on Day 1.
|
DE+Placebo_5m (Part II)
n=9 participants at risk
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.
|
DE+Placebo+Placebo (Part II)
n=3 participants at risk
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.
|
DE+1000mg_5m (Dose group5 - Part II)
n=9 participants at risk
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.
|
DE+2000mg_5m (Dose group6 - Part II)
n=9 participants at risk
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.
|
DE+4000mg_5m (Dose group7 - Part II)
n=9 participants at risk
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.
|
DE+2500mg+2500mg (Dose group8 - Part II)
n=9 participants at risk
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.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Investigations
Blood creatine phosphokinase increased
|
16.7%
1/6 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/2 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/6 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/6 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/6 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/6 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/9 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/3 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/9 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/9 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/9 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
0.00%
0/9 • From first drug administration until 13 weeks after the last drug administration, upto 98 days (Part-I) & upto 108 days (Part-II)
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER