A Study to Evaluate the Appropriateness of the Voriconazole Dosing Regimen

A Pilot Study to Evaluate the Appropriateness of the Voriconazole Dosing Regimen Based on the Population Pharmacokinetic Model and the Influence of Sex on the Pharmacokinetics of Voriconazole

A pilot study was performed to evaluate the appropriateness of the voriconazole dosing regimen based on the population pharmacokinetic model and the influence of sex on the pharmacokinetics of voriconazole

Study Overview

• Status: Completed
• Conditions: Fungal Infection
• Intervention / Treatment: Drug: Voriconazole Oral Product (Vfend®)

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital Clinical Trial Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Those who have been informed of the nature of the trial and have voluntarily agreed to participate in this study and have signed an IRB approved consent before all screening tests
• Healthy Korean male and female volunteers aged 20 to 45
• Those with a body weight of 50 kg or more and less than 90 kg and a body mass index (BMI) of 18 or more and less than 27 (BMI(kg/m2) = body weight (kg)/{height(m)}2
• CYP2C19 EM or PM

Exclusion Criteria:

• Subjects with clinical evidence of significant respiratory, circulatory, renal, hepatic, endocrine, blood, neuropsychiatric, skeletal or other chronic diseases, alcohol or drug addiction
• Subjects with a history of gastrointestinal disorders (Crohn's disease, ulcers, acute or chronic pancreatitis, etc.) or gastrointestinal surgery (excluding simple cecal surgery or hernia surgery) that may affect the absorption of the test drug
• Those with a history of substance abuse within the last 2 months
• Those who have taken any prescribed medicines or herbal medicines within 2 weeks prior to the date of the first medicines, or those taking any general medicines (OTC) or vitamin preparations (eligible if the other conditions are reasonable according to the judgment of the investigator)
• Those who donate blood within 30 days before the date of the first dose or who have participated in the clinical study of other clinical trial drugs or marketed drugs within 3 months
• Those who have had significant adverse reactions such as hypersensitivity reactions to azole drugs including drugs for clinical research
• Those who are not planning on or planning to have a pregnancy during the trial and are not able to use a recognized method of contraception (eg, sterilization surgery of the person and partner, intrauterine contraceptive device, or diaphragm contraception (such as diaphragm or condom use)
• Persons who are continuously drinking (21 units / week, 1 unit = 10 g of pure alcohol) or who can not abstain from 3 days before the first dose to the end of the clinical trial
• Those who smoked more than 10 cigarettes per day for the last 3 months or who can not quit smoking 3 days before the first dose
• Those who consume grapefruit / caffeine-containing food within 3 days of the first dose or who cannot be prohibited during the clinical study period
• Screening tests for urine pregnancy (β-hCG) positive or lactating women
• Those with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
• A person who is found to be unsuitable for participation in clinical research due to safety laboratory results or other reasons

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Voriconazole TBD mg tablet orally, every 12 hours for 7 days	Drug: Voriconazole Oral Product (Vfend®); To be determined mg of Voriconazole (Vfend®, anti-fungal agent)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration (Cmax)	Pharmacokinetic sampling after administration of drugs from day 1 to day 7	Day 1 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours, Day 5 12 hours, Day 6 0, 12 hours, Day 7 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours
Area under the plasma concentration versus time curve from the time of dosing to the last measurable concentration (AUClast)	Pharmacokinetic sampling after administration of drugs from day 1 to day 7	Day 1 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours, Day 5 12 hours, Day 6 0, 12 hours, Day 7 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic polymorphisms of CYP2C9 and CYP3A4	Exploratory evaluation	Day 1 0 hour
Hepatic safety marker of miRNA-122	Exploratory safety evaluation	Day 1 0 hour, Day 5 12 hour, Day 7 12 hour
Safety and tolerability evaluation by monitoring adverse events (number of subjects and cases)	Safety and tolerability evaluation	Day 1 to Day 12
Physical examination (list of current medications)	Safety and tolerability evaluation	Day 1 to Day 12
Physical examination (list of any symptoms or pain)	Safety and tolerability evaluation	Day 1 to Day 12
Physical examination (Medical and surgical history)	Safety and tolerability evaluation	Day 1 to Day 12
Evaluation of Vital signs (body temperature °C)	Safety and tolerability evaluation	Day 1 to Day 12
Evaluation of Vital signs (blood pressure mmHg)	Safety and tolerability evaluation	Day 1 to Day 12
Evaluation of Vital signs (pulse (heart rate, beats per minute))	Safety and tolerability evaluation	Day 1 to Day 12
Evaluation of Vital signs (breathing rate (respiratory rate, beats per minute))	Safety and tolerability evaluation	Day 1 to Day 12
Safety and tolerability evaluation by 12-lead ECG (P wave, PR interval, QRS complex, J-point, ST segment, T wave, Corrected QT interval, U wave)	Safety and tolerability evaluation	Day 1 to Day 12
number of participants with abnormal laboratory values (hematologic, chemical, urine)	Safety and tolerability evaluation	Day 1 to Day 12

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2018
• Primary Completion (Actual): October 28, 2018
• Study Completion (Actual): October 28, 2018

Study Registration Dates

• First Submitted: November 23, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Actual): November 30, 2018
• Last Update Submitted That Met QC Criteria: November 29, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; 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: Voriconazole_CYP2C19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No