Phase I Clinical Trial for Comparison of Pharmacokinetic Characteristics of Vorico Injection 200mg(Voriconazole) and Vfend® IV 200mg for Single Dose Crossover Intravenous Infusion in Healthy Volunteers

Phase I Clinical Trial for Comparison of Pharmacokinetic Characteristics of Vorico Injection 200mg(Voriconazole) and Vfend® IV 200mg for Single Dose Crossover Intravenous Infusion in Healthy Volunteers

Study Overview

• Status: Completed
• Conditions: Fungal Infections; Candida Infections; Aspergillus Infections
• Intervention / Treatment: Drug: Vorico Injection 200mg(Voriconazole); Drug: Vfend®(Voriconazole) IV 200mg

Detailed Description

To healthy volunteers subjects of twenty four(24), following treatments are administered dosing in each period injected wash-out period is a minimum of 7days. Treatment A(Test Drug): Vorico Injection 200mg(Voriconazole) for Single Dose Treatment B(Reference Drug): Vfend® IV 200mg for Single Dose Pharmacokinetic blood samples are collected up to 24hrs.

Safety and pharmacokinetic are assessed.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A healthy person whose age is in between 19 to 55 during the screening tests
2. Whose weight is more than 55 kg, BMI is over 18.5 and under 30.0 during the screening test. (BMI (kg/m2) = weight (kg) / {height (m)}2)
3. Who is completely informed and understand about this clinical trial, voluntarily participating it, and signed to follow the given instructions
4. Who is proven to fit into the clinical trial following by physical examination, ECG (electrocardiogram), clinical laboratory test, medical examination

5. Who agreed to do birth control during testing

   • A male who did not have vasectomy has to follow the clinically proven contraceptive methods* listed under, and who agreed not to donate sperm during the test

     * Clinically proven contraceptive method: intrauterine device (ex. Lippes Loop, Minera), chemical contraceptive (spermicides) for use with physical contraceptive method (males or females), contraceptive implants (ex. Implanon), tubal ligation or laparoscopy (common methods of tubal ligation)

   • A woman of childbearing age who agreed on constant use of a medically disproven Dual Protection method** and spermicides except hormonal contraceptive, and who also agreed not to breastfeed.

     • A Dual Protection method: use of condoms, the Intrauterine Contraceptive Device, the diaphragm, the cervical cap, in the case where a sexual partner had vasectomy over 3 months ago (from the date of initial screening) or a sexual partner had been medically diagnosed sterile.

Exclusion Criteria:

1. A person who has a history of clinically significant cardiovascular, respiratory, liver, kidney, endocrine system, immune system, urinary system diseases, blood-tumor diseases, mental illness.
2. Who has a history of hypersensitivity reactions to antifungal drugs including voriconazole or similar series or other excipient ingredients (aspirin, antibiotics, etc.)
3. Who has genetics issues on galactose intolerance, Lapp lactose deficiency, or glucose-galactose malabsorption
4. Who has a history of gastrointestinal disease (Crohn's disease, ulcer, acute or chronic pancreatitis, etc.) or gastrointestinal surgery (other than simple appendectomy and herniotomy)
5. A person whose electrocardiogram value includes QTc > 440 msec, PR < 110 msec or PR > 200 msec, QRS < 60 msec or QRS > 110 msec after screening, or who show clinically significant opinion.

6. Who falls under the following results

   1. AST, ALT are exceeded over 1.5x the upper limit of the normal range
   2. Total bilirubin is exceeded over 1.5x the upper limit of the normal range
7. Who shows the vital sign values of more than 140 mmHg or less than 90 mmHg in systolic pressure or more than 100 mmHg or less than 60 mmHg in diastolic blood pressure
8. Who has history of drug abuses or shows a positive result in the urinary drug screen
9. Who took any prescribed drugs, medicinal plants within the 2 weeks before the first day of dosing or takes any over-the-counter drugs or vitamin supplements within 1 week (but, if other conditions are met, they can still participate in the clinical test through the researcher's judgment)
10. Who took other investigational drugs or bioequivalence drugs within 3 months before the first day of dosing
11. Who participated in whole blood donation within 2 months before the first of dosing, or platelet donations within 1 months. Who received blood a month before the first day of dosing
12. Who constantly drinks alcohol (over 21 units/week, 1 unit = 10 g of pure alcohol) or cannot stop drinking alcohol during the clinical test.
13. Who smokes more than 10 cigarettes per day, or who cannot quit smoking when hospitalized
14. Who absorb caffeinated drinks (coffee, tea (black or green tea), soda, coffee flavored milk, energy drinks, etc.) or cannot stop absorbing them 24 hours before hospitalization until discharging
15. Who takes drug metabolism drug like barbital drugs which inhibit or activate the metabolism or drugs, or who takes one of the following drugs: St. John's Wort, rifabutin, rifampicin, carbamazepine, phenobarbital, high-dose of ritonavir, terfenadine, astemizole, cisapride, pimozide, quinidine, sirolimus, ergot, alkaloid (ergotamine, dihydroergotamine), efavirenz
16. Who was having foods (especially grapefruit or products contain grapefruit) that can influence the drug absorption, distribution, metabolism, and excretion within 7 days from the first day of dosage
17. A woman who is pregnant, shows positive result in serum/urine test, or who is breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TR Group; Test drug: Vorico Injection 200mg(Voriconazole) Wash out: 7 days Reference drug: Vfend® IV 200mg	Drug: Vorico Injection 200mg(Voriconazole); Vorico Injection 200mg(Voriconazole) to administered intravenously once; Drug: Vfend®(Voriconazole) IV 200mg; Vfend®(Voriconazole) IV 200mg to administered intravenously once
Experimental: RT group; Reference drug: Vfend® IV 200mg Wash out: 7 days Test drug: Vorico Injection 200mg(Voriconazole)	Drug: Vorico Injection 200mg(Voriconazole); Vorico Injection 200mg(Voriconazole) to administered intravenously once; Drug: Vfend®(Voriconazole) IV 200mg; Vfend®(Voriconazole) IV 200mg to administered intravenously once

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Voriconazole	The blood sampleing coleected from the subjects was analyzed and result was obtained.	0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs
AUCt of Voriconazole	The blood sampleing coleected from the subjects was analyzed and result was obtained.	0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax of Voriconazole	The blood sampleing coleected from the subjects was analyzed and result was obtained.	0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs
AUCinf of Voriconazole	The blood sampleing coleected from the subjects was analyzed and result was obtained.	0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs
AUCt/AUCinf	The blood sampleing coleected from the subjects was analyzed and result was obtained.	0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs
Kel (Elemination Rate Constant)	The blood sampleing coleected from the subjects was analyzed and result was obtained.	0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs
t1/2	The blood sampleing coleected from the subjects was analyzed and result was obtained.	0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical

Publications and helpful links

General Publications

• Cho SH, Kim CW, Nam MS. Pharmacokinetics and Safety of Two Voriconazole Formulations after Intravenous Infusion in Healthy Korean Volunteers. Infect Chemother. 2020 Jun;52(2):204-211. doi: 10.3947/ic.2020.52.2.204. Epub 2020 May 29.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: December 13, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimate): December 16, 2015

Study Record Updates

• Last Update Posted (Actual): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Candidiasis; 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: 151HPS14014