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Therapeutic Drug Monitoring (TDM) of Voriconazole and Correlation With CYP2C19 Genotype in Korean Populations

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ClinicalTrials.gov Identifier: NCT00673348
Recruitment Status : Unknown
Verified June 2008 by The Catholic University of Korea.
Recruitment status was:  Recruiting
First Posted : May 7, 2008
Last Update Posted : July 24, 2008
Sponsor:
Information provided by:
The Catholic University of Korea

Brief Summary:
Voriconazole (VCZ), the antifungal drug active against Candida and Aspergillus is a substrate of CYP2C19, whose proportion of poor metabolizers is about ~20% in Asian population. The AUC's of VCZ differs over 4 folds by CYP2C19 genotypes of homozygotic wild type, heterozygote, and homozygotic poor metabolizers. The Asian population enrolled in the metabolism of VCZ were mainly Japanese and Chinese, without Korean subjects. The proportion of poor metabolizers in Korean population is known to be around 12% (Pharmacogenetics. 1996 Dec;6(6):547-51). The importance of CYP2C19 genotypes on the pharmacokinetics (PK) of voriconazole is well established, Hence, it is desirable to individualize the dosage regimen of VCZ according to the genotypes of patients. Fungal infection in immunocompromised patients is a life threatening condition which needs critical care. Although the PK change by genotypes are well known, its clinical implication or need for different dosage regimen by genotypes is not established, yet.

Condition or disease
Mycoses Neutropenia Bone Marrow Transplantation

Detailed Description:
The investigators are trying to set up voriconazole (VCZ) therapeutic drug monitoring (TDM) & establish relationship with efficacy and safety in Korea. The investigators also want to propose the optimal dosage regimen for VCZ over different genotypes of CYP2C19 in the immunocompromised patients in Korea.

Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Prospective Observational Study of Plasma Voriconazole Concentration Measurement and Its Correlation With CYP2C19 Genotype in Korean Patients
Study Start Date : May 2008
Estimated Primary Completion Date : April 2009
Estimated Study Completion Date : April 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Group/Cohort
1
Patients suspected of invasive fungal infection (proven or probable cases) with immunocompromised state (for example, during neutropenia, receiving HSCT) in Catholic Hematopoietic Stem Cell Transplantation [HSCT] Center in Seoul, Korea.



Primary Outcome Measures :
  1. To regular setting of voriconazole TDM & establish relationship with efficacy and safety [ Time Frame: Prospective ]

Secondary Outcome Measures :
  1. To apply population pharmacokinetic-pharmacodynamic modeling and simulation technique on the clinical research of antifungal drugs. [ Time Frame: Prospective ]

Biospecimen Retention:   Samples With DNA
  • Two times of venous blood sampling will be carried out at steady state. Three ml of venous blood is sampled right before the morning dose (trough sampling). The second sampling is carried out at any time point within 2-4 hours after the morning dose (peak sampling). To obtain the exact dose and sampling history, at least three dosing times around the trough and peak sampling will be recorded to the minute. Sampling time will also be recorded as clock time.
  • Genotyping of CYP2C19 will also be performed using 3 ml of peripheral blood sampled into EDTA tubes.


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Ages Eligible for Study:   15 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients suspected of invasive fungal infection (proven or probable cases) with immunocompromised state (for example, during neutropenia, receiving HSCT) in Catholic Hematopoietic Stem Cell Transplantation [HSCT] Center in Seoul, Korea.
Criteria

Inclusion Criteria:

  • Immunocompromised adults who are treated with voriconazole due to proven or probable invasive fungal infections

Exclusion Criteria:

  • Patients who have been treated with other investigational drugs
  • Patients with liver dysfunction (aminotransferase level ≥ 5 times the upper limit of normal, bilirubin or alkaline phosphatase level > 3 times the upper limit of normal)
  • Patients with renal dysfunction (Cr level > 2.5 times the upper limit of normal)
  • Pregnant women
  • Patients younger than 15 years of age

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): NCT00673348


Contacts
Contact: Dong-Gun Lee, M.D., Ph.D. 82-2-3779-1114 ext 1099 symonlee@catholic.ac.kr
Contact: Dong-Seok Yim, M.D., Ph.D. 82-2-590-1114 ext 1201 yimds@catholic.ac.kr

Locations
Korea, Republic of
St. Mary's Hospital Not yet recruiting
Seoul, Korea, Republic of, 150-713
Contact: Dong-Gun Lee, M.D., Ph.D.    82-2-3779-1114 ext 1099    symonlee@catholic.ac.kr   
Principal Investigator: Dong-Gun Lee, M.D., Ph.D.         
St. Mary's Hospital Recruiting
Seoul, Korea, Republic of, 150-713
Contact: Hae-Young Youn, Pharm D    82-2-3779-1114 ext 1216    baram@catholic.ac.kr   
Sponsors and Collaborators
The Catholic University of Korea
Investigators
Principal Investigator: Dong-Gun Lee, M.D., Ph.D. St. Mary's Hospital, The Catholic Univ. of Korea

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dong-Gun Lee / Assistant Professor, Division of Infectious Diseases, Department of Internal Medicine
ClinicalTrials.gov Identifier: NCT00673348     History of Changes
Other Study ID Numbers: VCZ_TDM_Korea
First Posted: May 7, 2008    Key Record Dates
Last Update Posted: July 24, 2008
Last Verified: June 2008

Keywords provided by The Catholic University of Korea:
Mycoses
Voriconazole

Additional relevant MeSH terms:
Mycoses
Neutropenia
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Voriconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors