Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003611-66 | EudraCT Number | EudraCT |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The primary objective is to investigate the safety, tolerability and pharmacokinetics of BI 655075 following intravenous administration of single rising doses of BI 655075 when administered alone and after administration of dabigatran.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BI 655075 | Experimental |
| |
| Placebo | Placebo Comparator |
| |
| BI 655075 with dabigatran | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dabigatran | Drug |
| ||
| BI 655075 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Drug Related Adverse Events (AE) | Frequency of subjects with related adverse events (AE) by treatment | AEs occurring until end of follow-up (Up to 3 months after last drug administration) |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax (Maximum Measured Concentration) for Idarucizumab | Cmax (maximum measured concentration) for idarucizumab | -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h |
| Tmax (Time From Dosing to Maximum Measured Concentration) for Idarucizumab |
Not provided
Inclusion criteria:
1. Healthy male subjects
Exclusion criteria:
1. Any relevant deviation from healthy conditions
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1321.1.1 Boehringer Ingelheim Investigational Site | Antwerp | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28230262 | Derived | Norris S, Ramael S, Ikushima I, Haazen W, Harada A, Moschetti V, Imazu S, Reilly PA, Lang B, Stangier J, Glund S. Evaluation of the immunogenicity of the dabigatran reversal agent idarucizumab during Phase I studies. Br J Clin Pharmacol. 2017 Aug;83(8):1815-1825. doi: 10.1111/bcp.13269. Epub 2017 Apr 6. | |
| 26088268 | Derived |
Not provided
Not provided
Not provided
The study is conducted in two parts:
Parts 1 and 2 had a single rising dose design; subjects in Part 3 received 2 single doses 1 h apart.
Part 1: 8 subjects per dose group Part 2: 12 subjects per dose group Part 3: 12 subjects per dose group
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo 1 h | One single intravenous long infusion (1 h) of Idarucizumab Placebo This is administered during Part 1 of the study |
| FG001 | 20 mg Idarucizumab 1h | Dose group 1: One single intravenous long infusion (1 h) of 20 mg Idarucizumab verum This is administered during Part 1 of the study |
| FG002 | 60 mg Idarucizumab 1h | Dose group 2: One single intravenous long infusion (1 h) of 60 mg Idarucizumab verum This is administered during Part 1 of the study |
| FG003 | 200 mg Idarucizumab 1h | Dose group 3: One single intravenous long infusion (1 h) of 200 mg Idarucizumab verum This is administered during Part 1 of the study |
| FG004 | 600 mg Idarucizumab 1h | Dose group 4: One single intravenous long infusion (1 h) of 600 mg Idarucizumab verum This is administered during Part 1 of the study |
| FG005 | 1.2 g Idarucizumab 1h | Dose group 5: One single intravenous long infusion (1 h) of 1.2 g Idarucizumab verum This is administered during Part 1 of the study |
| FG006 | 2 g Idarucizumab 1h | Dose group 6: One single intravenous long infusion (1 h) of 2 g Idarucizumab verum This is administered during Part 1 of the study |
| FG007 | 3 g Idarucizumab 1h | Dose group 7: One single intravenous long infusion (1 h) of 3 g Idarucizumab verum This is administered during Part 1 of the study |
| FG008 | 4 g Idarucizumab 1h | Dose group 8: One single intravenous long infusion (1 h) of 4 g Idarucizumab verum This is administered during Part 1 of the study |
| FG009 | 6 g Idarucizumab 1h | Dose group 9: One single intravenous long infusion (1 h) of 6 g Idarucizumab verum This is administered during Part 1 of the study |
| FG010 | 8 g Idarucizumab 1h | Dose group 10: One single intravenous long infusion (1 h) of 8 g Idarucizumab verum This is administered during Part 1 of the study |
| FG011 | Placebo 5min | One single intravenous short infusion (5 min) of Idarucizumab Placebo This is administered during Part 1 of the study |
| FG012 | 1 g Idarucizumab 5min | Dose group 11: One single intravenous short infusion (5 min) of 1 g Idarucizumab verum This is administered during Part 1 of the study |
| FG013 | 2 g Idarucizumab 5min | Dose group 12: One single intravenous short infusion (5 min) of 2 g Idarucizumab verum This is administered during Part 1 of the study |
| FG014 | 4 g Idarucizumab 5min | Dose group 13: One single intravenous short infusion (5 min) of 4 g Idarucizumab verum This is administered during Part 1 of the study |
| FG015 | DE+ Placebo 5min | One single intravenous short infusion (5 min) of Idarucizumab Placebo administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| FG016 | DE+ 1 g Idarucizumab 5min | Dose group 14: One single intravenous short infusion (5 min) of 1 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| FG017 | DE+ 2 g Idarucizumab 5min | Dose group 15: One single intravenous short infusion (5 min) of 2 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| FG018 | DE+ 4 g Idarucizumab 5min | Dose group 16: One single intravenous short infusion (5 min) of 4 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| FG019 | DE+ Placebo+ Placebo | Two short intravenous infusions (5 min each) of Idarucizumab Placebo administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 3 of the study DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| FG020 | DE+ 5 g + 2.5 g Idarucizumab | Dose group 17: Two short intravenous infusions (5 min each) of 7.5 g Idarucizumab verum administered (5 g + 2.5 g 1 h later) at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 3 of the study DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated Set (TS): All randomised subjects who received 1 dose of trial medication were included in the treated set
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo 1 h | One single intravenous long infusion (1 h) of Idarucizumab Placebo This is administered during Part 1 of the study |
| BG001 | 20 mg Idarucizumab 1h | Dose group 1: One single intravenous long infusion (1 h) of 20 mg Idarucizumab verum This is administered during Part 1 of the study |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Secondary | Cmax (Maximum Measured Concentration) for Idarucizumab | Cmax (maximum measured concentration) for idarucizumab | Pharmacokinetic set (PKS) comprises of all subjects (with evaluable observations) in the TS who provided at least 1 PK endpoint and had no important protocol violations relevant to the evaluation of PK and additionally for Part 2 and 3 had no emesis with onset at or before twice the median tmax of dabigatran. | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h |
|
AEs occurring until end of follow-up (Up to 3 months after last drug administration)
AEs occurring between first administration of BI 655075 (5g) and second administration of BI 655075 2.5g are presented separately (shown under "DE + 5g"), and AEs occurring between second administration of BI 655075 2.5g and date of day after trial completion at 0:00h from this group of subjects are presented separately shown under DE+5g+2.5g.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo 1 h | One single intravenous long infusion (1 h) of Idarucizumab Placebo |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
There is only one group of subjects in study part 3 receiving active treatment. However, AE table displays the AEs occurring in different phases separately.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
Not provided
| ID | Term |
|---|---|
| D000069604 | Dabigatran |
| C000594745 | idarucizumab |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug |
|
tmax (time from dosing to maximum measured concentration) for idarucizumab |
| -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h |
| AUC0-inf (Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity) for Idarucizumab | AUC0-inf (area under the concentration-time curve from time 0 extrapolated to infinity) for idarucizumab | -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h |
| Aet1-t2 (Amount of Idarucizumab Eliminated in Urine From Time Point t1 to Time Point t2) | Aet1-t2 (amount of idarucizumab eliminated in urine from time point t1 to time point t2) Ae(0-7h) is presented for dose groups with 1 h infusion and Ae(0-4h) is presented for dose groups with 5 min infusion. | Up to 7 hours |
| Aet1-t2,ss (Amount of Dabigatran Etexilate Eliminated in Urine From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4 for Sum Dabigatran | Aet1-t2,ss (amount of dabigatran etexilate eliminated in urine from time point t1 to time point t2, at steady state) on Day 3 and Day 4 Ae(0-12h,ss) of sum dabigatran | Intervals 0-2, 2-6, 6-10, 10-12 hours on Day 3 post dabigatran treatment and -2 to -0:05, -0:05 to 4, 4-8, 8-10, 10-12, 12-24, 24-48, 48-72 on Day 4 post Idarucizumab treatment |
| C1.92,ss, C2,ss, C2.5,ss, C6,ss, and C12,ss (Concentration of the Unbound Sum Dabigatran in Plasma at Steady State) | Concentrations of unbound sum dabigatran in plasma after 1.92 to 12 h, at steady state of dabigatran, on Day 4 are presented. The endpoint refers to unbound sum dabigatran at several time points. The intended pharmacodynamic effect of idarucizumab is to reduce the concentration of this measure to levels below the lower limit of quantification (BLQ). "BLQ" values are not considered in the calculation of descriptive statistics; and therefore bias the result. This is the reason for applying the 2/3 rule to obtain reliable results. 2/3 rule states that, Statistics of PK parameters are only estimated when at least 2/3 of the data are evaluable. | 1.92 hours (h), 2 h, 2.5 h, 6 h and 12 h on Day 4 |
| AUCt1-t2,ss (Area Under the Concentration-time Curve for the Unbound Sum Dabigatran in Plasma From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4 | AUC(2-12),ss ((area under the concentration-time curve for the idarucizumab in plasma from time point 2 to 12 h )) on Day 3 and Day 4 | 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h |
| AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 2 of the Study | AUECt1-t2 (area under the effect curve from time point t1=2 hours to time point t2=12 hours) on Day 3 and Day 4 (determined under consideration of the baseline value). Ratio of above baseline AUEC(2-12) on Day 4 to above baseline AUEC(2-12) on Day 3 is presented. This endpoint was determined for Activated Partial Thromboplastin time (aPTT), Dithiothreitol (dTT), Thrombin time (TT) and Ecarin clotting time (ECT) | 2hours-12 hours |
| AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 3 of the Study | AUECt1-t2 (area under the effect curve from time point t1=2 hours to time point t2=12 hours) on Day 3 and Day 4 (determined under consideration of the baseline value). Ratio of above baseline AUEC(2-12) on Day 4 to above baseline AUEC(2-12) on Day 3 is presented. This endpoint was determined for Activated Partial Thromboplastin time (aPTT) and Dithiothreitol (dTT) | 2hours-12 hours |
| Glund S, Stangier J, Schmohl M, Gansser D, Norris S, van Ryn J, Lang B, Ramael S, Moschetti V, Gruenenfelder F, Reilly P, Kreuzer J. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015 Aug 15;386(9994):680-90. doi: 10.1016/S0140-6736(15)60732-2. Epub 2015 Jun 15. |
| BG002 | 60 mg Idarucizumab 1h | Dose group 2: One single intravenous long infusion (1 h) of 60 mg Idarucizumab verum This is administered during Part 1 of the study |
| BG003 | 200 mg Idarucizumab 1h | Dose group 3: One single intravenous long infusion (1 h) of 200 mg Idarucizumab verum This is administered during Part 1 of the study |
| BG004 | 600 mg Idarucizumab 1h | Dose group 4: One single intravenous long infusion (1 h) of 600 mg Idarucizumab verum This is administered during Part 1 of the study |
| BG005 | 1.2 g Idarucizumab 1h | Dose group 5: One single intravenous long infusion (1 h) of 1.2 g Idarucizumab verum This is administered during Part 1 of the study |
| BG006 | 2 g Idarucizumab 1h | Dose group 6: One single intravenous long infusion (1 h) of 2 g Idarucizumab verum This is administered during Part 1 of the study |
| BG007 | 3 g Idarucizumab 1h | Dose group 7: One single intravenous long infusion (1 h) of 3 g Idarucizumab verum This is administered during Part 1 of the study |
| BG008 | 4 g Idarucizumab 1h | Dose group 8: One single intravenous long infusion (1 h) of 4 g Idarucizumab verum This is administered during Part 1 of the study |
| BG009 | 6 g Idarucizumab 1h | Dose group 9: One single intravenous long infusion (1 h) of 6 g Idarucizumab verum This is administered during Part 1 of the study |
| BG010 | 8 g Idarucizumab 1h | Dose group 10: One single intravenous long infusion (1 h) of 8 g Idarucizumab verum This is administered during Part 1 of the study |
| BG011 | Placebo 5min | One single intravenous short infusion (5 min) of Idarucizumab Placebo This is administered during Part 1 of the study |
| BG012 | 1 g Idarucizumab 5min | Dose group 11: One single intravenous short infusion (5 min) of 1 g Idarucizumab verum This is administered during Part 1 of the study |
| BG013 | 2 g Idarucizumab 5min | Dose group 12: One single intravenous short infusion (5 min) of 2 g Idarucizumab verum This is administered during Part 1 of the study |
| BG014 | 4 g Idarucizumab 5min | Dose group 13: One single intravenous short infusion (5 min) of 4 g Idarucizumab verum This is administered during Part 1 of the study |
| BG015 | DE+ Placebo 5min | One single intravenous short infusion (5 min) of Idarucizumab Placebo administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| BG016 | DE+ 1 g Idarucizumab 5min | Dose group 14: One single intravenous short infusion (5 min) of 1 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| BG017 | DE+ 2 g Idarucizumab 5min | Dose group 15: One single intravenous short infusion (5 min) of 2 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| BG018 | DE+ 4 g Idarucizumab 5min | Dose group 16: One single intravenous short infusion (5 min) of 4 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| BG019 | DE+ Placebo+ Placebo | Two short intravenous infusions (5 min each) of Idarucizumab Placebo administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 3 of the study DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| BG020 | DE+ 5 g + 2.5 g Idarucizumab | Dose group 17: Two short intravenous infusions (5 min each) of 7.5 g Idarucizumab verum administered (5 g + 2.5 g 1 h later) at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 3 of the study DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| BG021 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 |
| 60 mg Idarucizumab 1h |
Dose group 2: One single intravenous long infusion (1 h) of 60 mg Idarucizumab verum This is administered during Part 1 of the study |
| OG002 | 200 mg Idarucizumab 1h | Dose group 3: One single intravenous long infusion (1 h) of 200 mg Idarucizumab verum This is administered during Part 1 of the study |
| OG003 | 600 mg Idarucizumab 1h | Dose group 4: One single intravenous long infusion (1 h) of 600 mg Idarucizumab verum This is administered during Part 1 of the study |
| OG004 | 1.2 g Idarucizumab 1h | Dose group 5: One single intravenous long infusion (1 h) of 1.2 g Idarucizumab verum This is administered during Part 1 of the study |
| OG005 | 2 g Idarucizumab 1h | Dose group 6: One single intravenous long infusion (1 h) of 2 g Idarucizumab verum This is administered during Part 1 of the study |
| OG006 | 3 g Idarucizumab 1h | Dose group 7: One single intravenous long infusion (1 h) of 3 g Idarucizumab verum This is administered during Part 1 of the study |
| OG007 | 4 g Idarucizumab 1h | Dose group 8: One single intravenous long infusion (1 h) of 4 g Idarucizumab verum This is administered during Part 1 of the study |
| OG008 | 6 g Idarucizumab 1h | Dose group 9: One single intravenous long infusion (1 h) of 6 g Idarucizumab verum This is administered during Part 1 of the study |
| OG009 | 8 g Idarucizumab 1h | Dose group 10: One single intravenous long infusion (1 h) of 8 g Idarucizumab verum This is administered during Part 1 of the study |
| OG010 | 1 g Idarucizumab 5min | Dose group 11: One single intravenous short infusion (5 min) of 1 g Idarucizumab verum This is administered during Part 1 of the study |
| OG011 | 2 g Idarucizumab 5min | Dose group 12: One single intravenous short infusion (5 min) of 2 g Idarucizumab verum This is administered during Part 1 of the study |
| OG012 | 4 g Idarucizumab 5min | Dose group 13: One single intravenous short infusion (5 min) of 4 g Idarucizumab verum This is administered during Part 1 of the study |
| OG013 | DE+ 1 g Idarucizumab 5min | Dose group 14: One single intravenous short infusion (5 min) of 1 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| OG014 | DE+ 2 g Idarucizumab 5min | Dose group 15: One single intravenous short infusion (5 min) of 2 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| OG015 | DE+ 4 g Idarucizumab 5min | Dose group 16: One single intravenous short infusion (5 min) of 4 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 2 of the study. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
| OG016 | DE+ 5 g + 2.5 g Idarucizumab | Dose group 17: Two short intravenous infusions (5 min each) of 7.5 g Idarucizumab verum administered (5 g + 2.5 g 1 h later) at or close to the steady state of Dabigatran etexilate (DE) 220 mg. This is administered during Part 3 of the study DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily |
|
|
| Secondary | Tmax (Time From Dosing to Maximum Measured Concentration) for Idarucizumab | tmax (time from dosing to maximum measured concentration) for idarucizumab | PKS (presented values are those subjects from the PKS with evaluable observations for this endpoint) | Posted | Median | Full Range | hours | -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h |
|
|
|
| Secondary | AUC0-inf (Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity) for Idarucizumab | AUC0-inf (area under the concentration-time curve from time 0 extrapolated to infinity) for idarucizumab | PKS (presented values are those subjects from the PKS with evaluable observations for this endpoint) | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | -2 hours(h), -0.5h, 0h, 2min(m), 5m, 10m, 15m,30m, 45m, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 48h, 72h |
|
|
|
| Secondary | Aet1-t2 (Amount of Idarucizumab Eliminated in Urine From Time Point t1 to Time Point t2) | Aet1-t2 (amount of idarucizumab eliminated in urine from time point t1 to time point t2) Ae(0-7h) is presented for dose groups with 1 h infusion and Ae(0-4h) is presented for dose groups with 5 min infusion. | PKS (presented values are those subjects from the PKS with evaluable observations for this endpoint) | Posted | Geometric Mean | Geometric Coefficient of Variation | μmol | Up to 7 hours |
|
|
|
| Primary | Number of Subjects With Drug Related Adverse Events (AE) | Frequency of subjects with related adverse events (AE) by treatment | Treated set | Posted | Number | participants | AEs occurring until end of follow-up (Up to 3 months after last drug administration) |
|
|
|
| Secondary | Aet1-t2,ss (Amount of Dabigatran Etexilate Eliminated in Urine From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4 for Sum Dabigatran | Aet1-t2,ss (amount of dabigatran etexilate eliminated in urine from time point t1 to time point t2, at steady state) on Day 3 and Day 4 Ae(0-12h,ss) of sum dabigatran | PKS (presented values are those subjects from the PKS with evaluable observations for this endpoint) | Posted | Geometric Mean | Geometric Coefficient of Variation | μg | Intervals 0-2, 2-6, 6-10, 10-12 hours on Day 3 post dabigatran treatment and -2 to -0:05, -0:05 to 4, 4-8, 8-10, 10-12, 12-24, 24-48, 48-72 on Day 4 post Idarucizumab treatment |
|
|
|
| Secondary | C1.92,ss, C2,ss, C2.5,ss, C6,ss, and C12,ss (Concentration of the Unbound Sum Dabigatran in Plasma at Steady State) | Concentrations of unbound sum dabigatran in plasma after 1.92 to 12 h, at steady state of dabigatran, on Day 4 are presented. The endpoint refers to unbound sum dabigatran at several time points. The intended pharmacodynamic effect of idarucizumab is to reduce the concentration of this measure to levels below the lower limit of quantification (BLQ). "BLQ" values are not considered in the calculation of descriptive statistics; and therefore bias the result. This is the reason for applying the 2/3 rule to obtain reliable results. 2/3 rule states that, Statistics of PK parameters are only estimated when at least 2/3 of the data are evaluable. | Pharmadynamic set (PDS) : The PDS was used for all PD analyses and comprised all subjects in the TS who provided at least 1 evaluable predose and 1 on-treatment observation for calculating ratio (PD endpoint) and who had no important protocol violations relevant to the evaluation of PD. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 1.92 hours (h), 2 h, 2.5 h, 6 h and 12 h on Day 4 |
|
|
|
| Secondary | AUCt1-t2,ss (Area Under the Concentration-time Curve for the Unbound Sum Dabigatran in Plasma From Time Point t1 to Time Point t2, at Steady State) on Day 3 and Day 4 | AUC(2-12),ss ((area under the concentration-time curve for the idarucizumab in plasma from time point 2 to 12 h )) on Day 3 and Day 4 | PKS (presented values are those subjects from the PKS with evaluable observations for this endpoint) | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h |
|
|
|
| Secondary | AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 2 of the Study | AUECt1-t2 (area under the effect curve from time point t1=2 hours to time point t2=12 hours) on Day 3 and Day 4 (determined under consideration of the baseline value). Ratio of above baseline AUEC(2-12) on Day 4 to above baseline AUEC(2-12) on Day 3 is presented. This endpoint was determined for Activated Partial Thromboplastin time (aPTT), Dithiothreitol (dTT), Thrombin time (TT) and Ecarin clotting time (ECT) | Pharmacodynamic set (PDS) : The PDS was used for all PD analyses and comprised all subjects in the TS who provided at least 1 evaluable predose and 1 on-treatment observation for calculating ratio (PD endpoint) and who had no important protocol violations relevant to the evaluation of PD. | Posted | Mean | Standard Deviation | ratio | 2hours-12 hours |
|
|
|
| Secondary | AUECt1-t2 (Area Under the Effect Curve From Time Point t1 to Time Point t2) on Day 3 and Day 4 (Determined Under Consideration of the Baseline Value) for Part 3 of the Study | AUECt1-t2 (area under the effect curve from time point t1=2 hours to time point t2=12 hours) on Day 3 and Day 4 (determined under consideration of the baseline value). Ratio of above baseline AUEC(2-12) on Day 4 to above baseline AUEC(2-12) on Day 3 is presented. This endpoint was determined for Activated Partial Thromboplastin time (aPTT) and Dithiothreitol (dTT) | Pharmacodynamic set (PDS) : The PDS was used for all PD analyses and comprised all subjects in the TS who provided at least 1 evaluable predose and 1 on-treatment observation for calculating ratio (PD endpoint) and who had no important protocol violations relevant to the evaluation of PD. | Posted | Mean | Standard Deviation | ratio | 2hours-12 hours |
|
|
|
| 0 |
| 21 |
| 7 |
| 21 |
| EG001 | 20 mg Idarucizumab 1h | One single intravenous long infusion (1 h) of 20 mg Idarucizumab verum | 0 | 6 | 2 | 6 |
| EG002 | 60 mg Idarucizumab 1h | One single intravenous long infusion (1 h) of 60 mg Idarucizumab verum | 0 | 6 | 2 | 6 |
| EG003 | 200 mg Idarucizumab 1h | One single intravenous long infusion (1 h) of 200 mg Idarucizumab verum | 0 | 6 | 5 | 6 |
| EG004 | 600 mg Idarucizumab 1h | One single intravenous long infusion (1 h) of 600 mg Idarucizumab verum | 0 | 5 | 2 | 5 |
| EG005 | 1.2 g Idarucizumab 1h | One single intravenous long infusion (1 h) of 1.2 g Idarucizumab verum | 0 | 6 | 1 | 6 |
| EG006 | 2 g Idarucizumab 1h | One single intravenous long infusion (1 h) of 2 g Idarucizumab verum | 0 | 12 | 4 | 12 |
| EG007 | 3 g Idarucizumab 1h | One single intravenous long infusion (1 h) of 3 g Idarucizumab verum | 0 | 6 | 3 | 6 |
| EG008 | 4 g Idarucizumab 1h | One single intravenous long infusion (1 h) of 4 g Idarucizumab verum | 0 | 6 | 0 | 6 |
| EG009 | 6 g Idarucizumab 1h | One single intravenous long infusion (1 h) of 6 g Idarucizumab verum | 0 | 6 | 1 | 6 |
| EG010 | 8 g Idarucizumab 1h | One single intravenous long infusion (1 h) of 8 g Idarucizumab verum | 0 | 6 | 2 | 6 |
| EG011 | Placebo 5min | One single intravenous short infusion (5 min) of Idarucizumab Placebo | 0 | 6 | 2 | 6 |
| EG012 | 1 g Idarucizumab 5min | One single intravenous short infusion (5 min) of 1 g Idarucizumab verum | 0 | 6 | 3 | 6 |
| EG013 | 2 g Idarucizumab 5min | Dose group 12: One single intravenous short infusion (5 min) of 2 g Idarucizumab verum | 0 | 6 | 2 | 6 |
| EG014 | 4 g Idarucizumab 5min | One single intravenous short infusion (5 min) of 4 g Idarucizumab verum | 0 | 6 | 3 | 6 |
| EG015 | DE (Dose Groups 14-16) | Dabigatran etexilate (220 mg; 2 capsules, each 110 mg) was administered to subjects orally, both in the mornings and evenings of Days 1 to 3 and in the morning of Day 4 in dose groups 14-16 | 0 | 35 | 20 | 35 |
| EG016 | DE+ Placebo 5min | One single intravenous short infusion (5 min) of Idarucizumab Placebo administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily | 0 | 9 | 1 | 9 |
| EG017 | DE+ 1 g Idarucizumab 5min | One single intravenous short infusion (5 min) of 1g of Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily | 0 | 9 | 4 | 9 |
| EG018 | DE+ 4 g Idarucizumab 5min | One single intravenous short infusion (5 min) of 4 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily | 0 | 8 | 4 | 8 |
| EG019 | DE+ 2 g Idarucizumab 5min | One single intravenous short infusion (5 min) of 2 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily | 0 | 9 | 4 | 9 |
| EG020 | DE (Dose Groups 17) | Dabigatran etexilate (220 mg; 2 capsules, each 110 mg) was administered to subjects orally, both in the mornings and evenings of Days 1 to 3 and in the morning of Day 4 in dose group 17 | 0 | 12 | 2 | 12 |
| EG021 | DE+ Placebo | One single intravenous short infusion (5 min) of Idarucizumab Placebo administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily | 0 | 3 | 0 | 3 |
| EG022 | DE+ Placebo+ Placebo | Two short intravenous infusions (5 min each) of Idarucizumab Placebo administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily | 0 | 3 | 1 | 3 |
| EG023 | DE+ 5 g | One single intravenous short infusion (5 min) of 5 g Idarucizumab verum administered at or close to the steady state of Dabigatran etexilate (DE) 220 mg. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily | 0 | 9 | 1 | 9 |
| EG024 | DE+ 5 g + 2.5 g Idarucizumab | Two short intravenous infusions (5 min each) of 7.5 g Idarucizumab verum administered (5 g + 2.5 g 1 h later) at or close to the steady state of Dabigatran etexilate (DE) 220 mg. DE is administered orally : Day 1 to 3: twice daily; Day 4: once daily | 0 | 9 | 3 | 9 |
| Bronchitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Skin reaction | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Glycosuria | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Asthenia | General disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Fatigue | General disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Influenza like illness | General disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Infusion site swelling | General disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Injection site erythema | General disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Injection site haematoma | General disorders | MEDDRA 16.1 | Systematic Assessment |
|
| Application site irritation | General disorders | MEDDRA 16.1 | Systematic Assessment |
|
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
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| C2,ss (N= 9, 6, NA, NA, 2, NA) |
|
| C2.5,ss (N= 9, NA, NA, NA, 2, NA ) |
|
| C6,ss (N= 9, 9, NA, NA, 2, NA) |
|
| C12,ss (N= 9, 9, NA, NA, 2, NA) |
|
| dTT |
|
| TT |
|
| ECT |
|