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

March 7, 2019 updated by: Boehringer Ingelheim

Open Label Phase I Trial in Healthy Chinese Male and Female Volunteers to Investigate Pharmacokinetics and Pharmacodynamics of Idarucizumab to Reverse Dabigatran Anticoagulant Activity

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.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Beijing, China, 100034
        • Peking University First Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: All Subjects
Dabigatran etexilate alone (days 1-4) and (days 8-10) and with Idarucizumab (day 11)
Days 1-4 and Day 8-11
Other Names:
  • PRADAXA, PRAZAXA
Day 11
Other Names:
  • PRAXBIND, Praxbind, Prizbind

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Measured Concentration of Idarucizumab in Plasma (Cmax)
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)
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
Time Frame: 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-∞)
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)
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)
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

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

Secondary Outcome Measures

Outcome Measure
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
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.

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.
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
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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 10, 2017

Primary Completion (Actual)

September 12, 2017

Study Completion (Actual)

September 12, 2017

Study Registration Dates

First Submitted

March 16, 2017

First Submitted That Met QC Criteria

March 20, 2017

First Posted (Actual)

March 22, 2017

Study Record Updates

Last Update Posted (Actual)

March 8, 2019

Last Update Submitted That Met QC Criteria

March 7, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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