Influence of Drug-drug Interactions on the Pharmacokinetics (PK) of Voriconazole

Clinical Trials to Evaluate the Influence of CYP2C19 Genotype and Drug-drug Interactions on the Pharmacokinetics of Voriconazole in Healthy Korean Male Volunteers (Part B)

To evaluate the drug-drug interaction between rifampicin and voriconazole according to CYP2C19 genotype quantitatively following a single oral administration of 200 mg voriconazole

Study Overview

• Status: Completed
• Conditions: Invasive Aspergillosis
• Intervention / Treatment: Drug: Voriconazole

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital Clinical Trial Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 1.Healthy male subjects aged 20 - 50 years.
• 2.A body mass index (BMI) in the range 17-28 kg/m2.
• 3.Sufficient ability to understand the nature of the study and any hazards of participating in it. Provide written informed consent after being fully informed about the study procedures.

Exclusion Criteria:

• 1.Presence or history of severe adverse reaction to any drug or a history of severe allergic disease.
• 2.Clinically relevant abnormal medical history that could interfere with the objectives of the study.
• 3.Presence or history of eye disease or eye field defect.
• 4.A subject with history of gastrointestinal disease or surgery (except simple appendectomy or repair of hernia), which can influence the absorption of the study drug.
• 5.A subject whose liver function test (AST, ALT, GGT, ALP, LDH) result is over 1.25 times of upper limit of normal range.
• 6.A subject whose SBP is over 140 mmHg or below 90 mmHg and DBP is over 100 mmHg or below 50 mmHg.
• 7.Presence or history of drug abuse.
• 8.Participation in other clinical trial within 2 months.
• 9.Use of a prescription medicine, herbal medicine within 2 weeks or over-the-counter medication within 1 week before first dose.
• 10.Blood donation during 2 months or apheresis during 1 month before the study.
• 11.Presence or history of alcohol abuse.
• 12.Smoking of more than 10 cigarettes/day.
• 13.Use of grapefruit juice, xanthine containing beverage, alcohol or smoking during restriction period.
• 14.Subject judged not eligible for study participation by investigator.

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CYP2C19 extensive metabolizer	Drug: Voriconazole; Day1: voriconazole 200 mg x 2, oral administration, Day2-7: rifampin 600 mg, once a day oral administration, Day8: voriconazole 200 mg x 2 + rifampin 600 mg, oral co-administration
Active Comparator: CYP2C19 poor metabolizer	Drug: Voriconazole; Day1: voriconazole 200 mg x 2, oral administration, Day2-7: rifampin 600 mg, once a day oral administration, Day8: voriconazole 200 mg x 2 + rifampin 600 mg, oral co-administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of voriconazole	Sample for concentration measurement conducted before and after rifampicin treatment as same manner	pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h post-dose

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: In-Jin Jang, M.D., Ph.D., Professor

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: March 2, 2010
• First Submitted That Met QC Criteria: March 2, 2010
• First Posted (Estimate): March 4, 2010

Study Record Updates

• Last Update Posted (Estimate): August 19, 2011
• Last Update Submitted That Met QC Criteria: August 17, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Aspergillosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Voriconazole
• Other Study ID Numbers: SNUCPT09_Vori2C19_B