CClinicalTrials.gg
CompletedNCT03086356Updated Mar 8, 2019Results posted

Study to Investigate the Pharmacokinetics (PK) and Pharmacodynamics (PD) of Idarucizumab in Chinese Healthy Male and Female Volunteers Who Had Taken Dabigatran Etexilate and Whose Plasma Concentrations of Dabigatran Were at or Close to Steady State

A Phase 1 interventional study of Dabigatran etexilate and Idarucizumab in Healthy Volunteers, sponsored by Boehringer Ingelheim. Completed at 1 site in China. Open to participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2019-03-08.

Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
12
Allocation
Not applicable
Ages
18 Years to 45 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Healthy Volunteers
03

In context

Lead sponsor

Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.

Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age >= 18 and Age \<= 45 years at screening
  • Healthy male and female based upon a complete medical history, including vital signs (Blood Pressure, Pulse Rate, and Body Temperature), 12-lead Electrocardiogram and clinical laboratory tests. Women of childbearing potential must be ready and able to use highly effective methods of birth control per International Committee on Harmonisation M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
  • Body weight >=50 kg with body mass index range >=19.0 and \<24.0 kg/m2 at Visit 1.
  • Signed and dated written informed consent in accordance with Good Clinical Practice and local legislation prior to admission to the trial.

Exclusion criteria

Exclusion criteria:

  • Any finding of the medical examination (including Blood Pressure, Pulse Rate, Body Temperature and Electrocardiogram) is deviating from normal and judged as clinically relevant by the investigator
  • Any evidence of a clinically relevant concomitant disease according to investigator's clinical judgement
  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
  • Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication (except appendectomy)
  • Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
  • History of relevant orthostatic hypotension, fainting spells or blackouts.
  • Chronic or relevant acute infections
  • History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) or immune system disease
  • Intake of drugs with a long half-life (> 24 hours) within at least 30 days or less than 10 half-lives of the respective drug prior to first trial drug administration
  • Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/corrected QT (QTc) interval.
  • Participation in another trial with investigational drug administration within 60 days prior to first trial drug administration
  • Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
  • Inability to refrain from smoking during hospitalization
  • Alcohol abuse (consumption of more than 20 g per day: e.g., 1 middle-sized bottles of beer, 1 gou [equivalent to 180 mL] of sake))
  • Drug abuse or positive drug screening
  • Blood donation (400 mL whole blood donation within 12 weeks, 200 mL whole blood donation or blood component donation within 4 weeks) prior to first trial drug administration
  • Intention to perform excessive physical activities within one week prior to first trial drug administration or during the trial
  • Any laboratory values outside the reference range that are of clinical relevance according to investigator's clinical judgement
  • Inability to comply with dietary regimen of trial site
  • A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF interval >450 ms)
  • A history of additional risk factors for torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
  • Positive HIV (human immunodeficiency virus) test result at screening examination
  • Positive testing for Hepatitis B Antigen and/or a positive Hepatitis C antibody test result at screening examination
  • Subjects considered unsuitable for inclusion by the investigator, e.g. are unable to understand and comply with trial requirements, or have any condition which in the opinion of the investigator would not allow safe participation in the trial.
  • Subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until 12 weeks after the trial completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female (intra-uterine device with spermicide. hormonal contraceptive since at least 8 weeks)
  • History or evidence of blood dyscrasia, haemorrhagic diathesis, severe thrombocytopenia, cerebrovascular haemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with haemorrhagic tendencies (e.g. cerebral aneurysm, dissecting aorta, central nervous system (CNS) trauma, retinopathy, nephrolithiasis)
  • Abnormal values for prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombocytes considered by the investigator or one of the co-investigators to be clinically relevant
  • Creatinine and estimated glomerular filtration rate (GFR) outside the normal range
  • Evidence of proteinuria
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
12 participants (actual)

Study arms

  • Experimental
    All Subjects

    Dabigatran etexilate alone (days 1-4) and (days 8-10) and with Idarucizumab (day 11)

    Drug: Dabigatran etexilate · Drug: Idarucizumab

Interventions

  • DrugDabigatran etexilate

    Days 1-4 and Day 8-11

    Also known as: PRADAXA, PRAZAXA

  • DrugIdarucizumab

    Day 11

    Also known as: PRAXBIND, Praxbind, Prizbind

06

What researchers measure

Primary outcomes

  1. Maximum Measured Concentration of Idarucizumab in Plasma (Cmax)

    Cmax, maximum measured concentration of idarucizumab in plasma

    Time frame: -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)

  2. 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 %)

    Time frame: Day 4 and day 11

  3. 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

    Time frame: -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)

  4. 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"

    Time frame: 0-2 h, 2-6 h, 6-10 h, 10-12 h,12-14h, 14-26 h, 26-50 h, 50-74 h after drug administration of dabigatran etexilate on Day 4

Secondary outcomes

  1. 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"

    Time frame: 0-2 h, 2-6 h, 6-10 h, 10-12 h,12-14h, 14-26 h, 26-50 h, 50-74 h after drug administration of dabigatran etexilate on Day 4 and Day 11.

  2. 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".

    Time frame: 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

07

Results

Posted Mar 8, 2019

Participant flow

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.

Participant flow — Overall Study
MilestoneDabigatran Etexilate+Idarucizumab
Started12
Completed12
Not completed0

Outcome measures

PrimaryMaximum Measured Concentration of Idarucizumab in Plasma (Cmax)

Cmax, maximum measured concentration of idarucizumab in plasma

Time frame:
-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)
Reported as:
Geometric mean · nanomoles (nmol) per litre (L)
Maximum Measured Concentration of Idarucizumab in Plasma (Cmax)
nanomoles (nmol) per litre (L)Dabigatran Etexilate+Idarucizumab
Maximum Measured Concentration of Idarucizumab in Plasma (Cmax)30900 ± 9.86
PrimaryFor 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 %)

Time frame:
Day 4 and day 11
Reported as:
Mean · hours
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
hoursDabigatran Etexilate+Idarucizumab
Day 48.23 ± 32.0
Day 110.118 ± 140
SecondaryFor 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"

Time frame:
0-2 h, 2-6 h, 6-10 h, 10-12 h,12-14h, 14-26 h, 26-50 h, 50-74 h after drug administration of dabigatran etexilate on Day 4 and Day 11.
Reported as:
Geometric mean · μg (microgram)
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
μg (microgram)Dabigatran Etexilate+Idarucizumab
Day 411700 ± 30.0
Day 1111000 ± 41.8
SecondaryFor 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".

Time frame:
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
Reported as:
Geometric mean · nanograms*hours/ milliliter
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
nanograms*hours/ milliliterDabigatran Etexilate+Idarucizumab
Day 41270 ± 37.0
Day 1111.6 ± 44.3
PrimaryArea 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

Time frame:
-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)
Reported as:
Geometric mean · nanomoles (nmol)*hours (h) per litre (L)
Area Under the Concentration-time Curve of Idarucizumab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
nanomoles (nmol)*hours (h) per litre (L)Dabigatran Etexilate+Idarucizumab
Area Under the Concentration-time Curve of Idarucizumab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)44200 ± 10.1
PrimaryAmount 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"

Time frame:
0-2 h, 2-6 h, 6-10 h, 10-12 h,12-14h, 14-26 h, 26-50 h, 50-74 h after drug administration of dabigatran etexilate on Day 4
Reported as:
Geometric mean · micromole (μmol)
Amount of Idarucizumab Eliminated in Urine Over the Time Interval From 0 to 72 Hours (h) (Ae0-72)
micromole (μmol)Dabigatran Etexilate+Idarucizumab
Amount of Idarucizumab Eliminated in Urine Over the Time Interval From 0 to 72 Hours (h) (Ae0-72)35.3 ± 57.1

Adverse events

Collected over Adverse events from the first intake of treatment until the end of treatment visit; up to 23 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dabigatran Etexilate+Idarucizumab0/12 (0%)0/12 (0%)12/12 (100%)
Most frequent other events
Most frequent other events
EventDabigatran Etexilate+Idarucizumab
Albumin urine presentInvestigations12/12
Alpha 1 microglobulin increasedInvestigations12/12
Protein urine presentInvestigations11/12
Activated partial thromboplastin time prolongedInvestigations10/12
Urine electrophoresis abnormalInvestigations10/12
Prothrombin level decreasedInvestigations4/12
HaematomaVascular disorders1/12
DiarrhoeaGastrointestinal disorders1/12
Blood triglycerides increasedInvestigations1/12

Baseline characteristics

Treated set (TS): The TS included all subjects who received at least 1 infusion of idarucizumab.

Age, Continuous
Age, Continuous(years)Dabigatran Etexilate+Idarucizumab
Mean35.6 ± 5.8
Sex: Female, Male
Sex: Female, Male(Participants)Dabigatran Etexilate+Idarucizumab
Female6
Male6
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Dabigatran Etexilate+Idarucizumab
American Indian or Alaska Native0
Asian12
Native Hawaiian or Other Pacific Islander0
Black or African American0
White0
More than one race0
Unknown or Not Reported0
08

Study locations

1 site
  • Peking University First Hospital
    Beijing, 100034, China
09

References and documents

Publications

  • 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. PubMed 32691242 ↗

Related links

Study documents

  • Study protocol · Mar 17, 2017
  • Statistical analysis plan · Sep 14, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 8, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03086356
Lead sponsor
Boehringer Ingelheim
Responsible party
Sponsor
First posted
Mar 22, 2017
Start date
May 10, 2017
Primary completion
Sep 12, 2017
Completion
Sep 12, 2017
Results posted
Mar 8, 2019
Last update
Mar 8, 2019

Study contacts

Boehringer Ingelheim
study chair · Boehringer Ingelheim

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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