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The primary objective of the trial is to investigate the pharmacokinetics and pharmacodynamics of idarucizumab in Chinese healthy male and female subjects following intravenous administration of idarucizumab followed by idarucizumab with 15 minutes interval when administered at or close to the steady state of dabigatran.
Another objective of this trial is to explore the effect idarucizumab on the PK (pharmacokinetic(s)) and PD (pharmacodynamic) parameters of dabigatran.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All Subjects | Experimental | Dabigatran etexilate alone (days 1-4) and (days 8-10) and with Idarucizumab (day 11) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dabigatran etexilate | Drug | Days 1-4 and Day 8-11 |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Measured Concentration of Idarucizumab in Plasma (Cmax) | Cmax, maximum measured concentration of idarucizumab in plasma | -0.017, 0.083, 0.167, 0.317, 0.417, 0.45, 0.583, 0.917, 1.417, 2.083, 3.083, 4.083, 6.083, 10.083, 12.083, 24.083, 48.083, 72.083 hours (h) |
| For Diluted Thrombin Time: Area After Subtraction of Baseline Area From Area Under the Effect Curve Over the Time Interval From 2 - 12 Hours (AUEC Above,2-12) on Day 4 and Day 11 | For diluted thrombin time: AUEC above,2-12 (area after subtraction of baseline area from area under the effect curve over the time interval from 2 - 12) on day 4 and day 11. The standard deviation (SD) presented is actually the percentage coefficient of variation (CV %) | Day 4 and day 11 |
| Area Under the Concentration-time Curve of Idarucizumab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞, area under the concentration-time curve of idarucizumab in plasma over the time interval from 0 extrapolated to infinity | -0.017, 0.083, 0.167, 0.317, 0.417, 0.45, 0.583, 0.917, 1.417, 2.083, 3.083, 4.083, 6.083, 10.083, 12.083, 24.083, 48.083, 72.083 hours (h) |
| Amount of Idarucizumab Eliminated in Urine Over the Time Interval From 0 to 72 Hours (h) (Ae0-72) | Ae0-72, amount of idarucizumab eliminated in urine over the time interval from 0 to 72 h. As per the protocol, day is counted as "Day 1 = 0:00" | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| For Sum Dabigatran: Amount of the Analyte Excreted in Urine at Steady State Over the Time Interval 0-74 Hours (Ae0-74,ss ) on Day 4 and Day 11 | For sum dabigatran: Ae0-74,ss (amount of the analyte excreted in urine at steady state over the time interval 0-74) on day 4 and day 11 if feasible. As per the protocol, day is counted as "Day 1 = 0:00" | 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. |
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Inclusion criteria:
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University First Hospital | Beijing | 100034 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32691242 | Derived | Wang Z, Zhao X, He P, Chen S, Jiang J, Harada A, Brooks S, Cui Y. Idarucizumab Reverses Dabigatran Anticoagulant Activity in Healthy Chinese Volunteers: A Pharmacokinetics, Pharmacodynamics, and Safety Study. Adv Ther. 2020 Sep;37(9):3916-3928. doi: 10.1007/s12325-020-01439-2. Epub 2020 Jul 20. |
| Label | URL |
|---|---|
| Related Info | View source |
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Healthy male and female volunteers, aged ≥18 and ≤45 years, body weight
≥50 kilograms (kg) with a Body Mass Index (BMI) in the range from ≥19 to <24 kilogram per square meter (kg/m2) were included in the trial.
This was a single-centre, open-label trial in 1 group of healthy volunteers. The trial included a 2-week treatment period during which the subjects were hospitalised at the trial site and a follow-up period of approximately 3 months.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dabigatran Etexilate+Idarucizumab | During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 17, 2017 | Sep 12, 2018 |
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| Idarucizumab | Drug | Day 11 |
|
|
| For Unbound Sum Dabigatran: Area Under the Concentration-time Curve of the Dabigatran in Plasma at Steady State Over the Time Interval 2 Hours-12 Hours | For unbound sum dabigatran: AUC 2-12,ss (Area under the concentration-time curve of the dabigatran in plasma at steady state over the time interval 2 hours-12 hours). As per the protocol, day is counted as "Day 1 = 0:00". | Day 4: 74h, 74.5h, 75h, 76h, 78h, 80h, 84h; Day 11: 242h, 242.083h, 242.25h, 242.333h 243.333h, 244h, 246h, 248h, 252h |
| COMPLETED |
|
| NOT COMPLETED |
|
Treated set (TS): The TS included all subjects who received at least 1 infusion of idarucizumab.
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| ID | Title | Description |
|---|---|---|
| BG000 | Dabigatran Etexilate+Idarucizumab | During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min) interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age at the time of informed consent | TS | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | TS | Count of Participants | Participants |
| |||||||||||||||||
| Race (NIH/OMB) | Ethnicity is not reported in this trial | TS | Count of Participants | Participants |
|
| 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 | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Measured Concentration of Idarucizumab in Plasma (Cmax) | Cmax, maximum measured concentration of idarucizumab in plasma | Pharmacokinetic set (PKS): The PKS included all subjects of the Treated set (TS) who had at least one Pharmacokinetic (PK) parameter analysed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomoles (nmol) per litre (L) | -0.017, 0.083, 0.167, 0.317, 0.417, 0.45, 0.583, 0.917, 1.417, 2.083, 3.083, 4.083, 6.083, 10.083, 12.083, 24.083, 48.083, 72.083 hours (h) |
|
|
| |||||||||||||||||||||||||
| Primary | For Diluted Thrombin Time: Area After Subtraction of Baseline Area From Area Under the Effect Curve Over the Time Interval From 2 - 12 Hours (AUEC Above,2-12) on Day 4 and Day 11 | For diluted thrombin time: AUEC above,2-12 (area after subtraction of baseline area from area under the effect curve over the time interval from 2 - 12) on day 4 and day 11. The standard deviation (SD) presented is actually the percentage coefficient of variation (CV %) | Pharmacodynamic set (PDS): The PDS included all subjects in the TS who provided at least one evaluable pre-dose and one on-treatment PD observation after the start of dabigatran administration. | Posted | Mean | Standard Deviation | hours | Day 4 and day 11 |
|
| ||||||||||||||||||||||||||
| Secondary | For Sum Dabigatran: Amount of the Analyte Excreted in Urine at Steady State Over the Time Interval 0-74 Hours (Ae0-74,ss ) on Day 4 and Day 11 | For sum dabigatran: Ae0-74,ss (amount of the analyte excreted in urine at steady state over the time interval 0-74) on day 4 and day 11 if feasible. As per the protocol, day is counted as "Day 1 = 0:00" | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | μg (microgram) | 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. |
|
| ||||||||||||||||||||||||||
| Secondary | For Unbound Sum Dabigatran: Area Under the Concentration-time Curve of the Dabigatran in Plasma at Steady State Over the Time Interval 2 Hours-12 Hours | For unbound sum dabigatran: AUC 2-12,ss (Area under the concentration-time curve of the dabigatran in plasma at steady state over the time interval 2 hours-12 hours). As per the protocol, day is counted as "Day 1 = 0:00". | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours/ milliliter | Day 4: 74h, 74.5h, 75h, 76h, 78h, 80h, 84h; Day 11: 242h, 242.083h, 242.25h, 242.333h 243.333h, 244h, 246h, 248h, 252h |
|
| ||||||||||||||||||||||||||
| Primary | Area Under the Concentration-time Curve of Idarucizumab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | AUC0-∞, area under the concentration-time curve of idarucizumab in plasma over the time interval from 0 extrapolated to infinity | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomoles (nmol)*hours (h) per litre (L) | -0.017, 0.083, 0.167, 0.317, 0.417, 0.45, 0.583, 0.917, 1.417, 2.083, 3.083, 4.083, 6.083, 10.083, 12.083, 24.083, 48.083, 72.083 hours (h) |
|
| ||||||||||||||||||||||||||
| Primary | Amount of Idarucizumab Eliminated in Urine Over the Time Interval From 0 to 72 Hours (h) (Ae0-72) | Ae0-72, amount of idarucizumab eliminated in urine over the time interval from 0 to 72 h. As per the protocol, day is counted as "Day 1 = 0:00" | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | micromole (μmol) | 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 |
|
|
Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dabigatran Etexilate+Idarucizumab | During the first part of the treatment period, dabigatran etexilate was administered alone. All subjects received 220 milligram (mg) dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 1 to 3) and a single 220 mg dose on Day 4. During the second part of the treatment period, after a washout period of 3 days, subjects again received dabigatran etexilate (capsule) orally twice daily for 3 days (from Days 8 to 10) and a single 220 mg dose on Day 11. Idarucizumab (solution for infusion) 2 short infusions of 2.5 grams (g) each, with a 15 minute (min)interval was administered intravenously approximately 2 hours (h) after the last dabigatran etexilate administration. | 0 | 12 | 0 | 12 | 12 | 12 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haematoma | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Albumin urine present | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Alpha 1 microglobulin increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Protein urine present | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Urine electrophoresis abnormal | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Prothrombin level decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA 20.0 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 14, 2017 | Sep 12, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000069604 | Dabigatran |
| C000594745 | idarucizumab |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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