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

NCT03086356 | Completed Phase 1 Results

• 1 other identifier: 1321.6
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (4)

• 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

Secondary Outcomes (2)

• 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

  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

  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

Study Arms (1)

All Subjects

EXPERIMENTAL

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

Drug: Dabigatran etexilate; Drug: Idarucizumab

Interventions

Dabigatran etexilate DRUG

Days 1-4 and Day 8-11

Also known as: PRADAXA, PRAZAXA

All Subjects

Idarucizumab DRUG

Day 11

Also known as: PRAXBIND, Praxbind, Prizbind

All Subjects

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Peking University First Hospital

Beijing, 100034, China

Location

Related Publications (1)

• 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.

  PMID: 32691242 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

Dabigatran; idarucizumab

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2017
• First Posted: March 22, 2017
• Study Start: May 10, 2017
• Primary Completion: September 12, 2017
• Study Completion: September 12, 2017
• Last Updated: March 8, 2019
• Results First Posted: March 8, 2019

Record last verified: 2019-03

Locations

CN (1)