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Trial record 17 of 333 for:    DABIGATRAN

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

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ClinicalTrials.gov Identifier: NCT03086356
Recruitment Status : Completed
First Posted : March 22, 2017
Results First Posted : March 8, 2019
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief 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.


Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Dabigatran etexilate Drug: Idarucizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Phase I Trial in Healthy Chinese Male and Female Volunteers to Investigate Pharmacokinetics and Pharmacodynamics of Idarucizumab to Reverse Dabigatran Anticoagulant Activity
Actual Study Start Date : May 10, 2017
Actual Primary Completion Date : September 12, 2017
Actual Study Completion Date : September 12, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: All Subjects
Dabigatran etexilate alone (days 1-4) and (days 8-10) and with Idarucizumab (day 11)
Drug: Dabigatran etexilate
Days 1-4 and Day 8-11
Other Name: PRADAXA, PRAZAXA

Drug: Idarucizumab
Day 11
Other Name: PRAXBIND, Praxbind, Prizbind




Primary Outcome Measures :
  1. 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

  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 [ 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 %)


  3. 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

  4. 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"



Secondary Outcome Measures :
  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 [ 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"


  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 [ 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".




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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03086356


Locations
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China
Peking University First Hospital
Beijing, China, 100034
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  Study Documents (Full-Text)

Documents provided by Boehringer Ingelheim:
Study Protocol  [PDF] March 17, 2017
Statistical Analysis Plan  [PDF] September 14, 2017


Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03086356     History of Changes
Other Study ID Numbers: 1321.6
First Posted: March 22, 2017    Key Record Dates
Results First Posted: March 8, 2019
Last Update Posted: March 8, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Dabigatran
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants