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

• Sponsor: Chong Kun Dang Pharmaceutical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02631954
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 12

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Aspergillus Infections; Candida Infections; Fungal Infections	Drug: Vorico Injection 200mg(Voriconazole); Drug: Vfend®(Voriconazole) IV 200mg	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Cmax of Voriconazole [0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs]

   The blood sampleing coleected from the subjects was analyzed and result was obtained.

2. AUCt of Voriconazole [0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs]

   The blood sampleing coleected from the subjects was analyzed and result was obtained.

Secondary Outcome Measures

1. Tmax of Voriconazole [0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs]

   The blood sampleing coleected from the subjects was analyzed and result was obtained.

2. AUCinf of Voriconazole [0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs]

   The blood sampleing coleected from the subjects was analyzed and result was obtained.

3. AUCt/AUCinf [0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs]

   The blood sampleing coleected from the subjects was analyzed and result was obtained.

4. Kel (Elemination Rate Constant) [0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs]

   The blood sampleing coleected from the subjects was analyzed and result was obtained.

5. t1/2 [0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs]

   The blood sampleing coleected from the subjects was analyzed and result was obtained.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

7. AST, ALT are exceeded over 1.5x the upper limit of the normal range

8. Total bilirubin is exceeded over 1.5x the upper limit of the normal range

9. 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

10. Who has history of drug abuses or shows a positive result in the urinary drug screen

11. 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)

12. Who took other investigational drugs or bioequivalence drugs within 3 months before the first day of dosing

13. 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

14. Who constantly drinks alcohol (over 21 units/week, 1 unit = 10 g of pure alcohol) or cannot stop drinking alcohol during the clinical test.

15. Who smokes more than 10 cigarettes per day, or who cannot quit smoking when hospitalized

16. 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

17. 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

18. 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

19. A woman who is pregnant, shows positive result in serum/urine test, or who is breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Inha University Hospital	Incheon		Korea, Republic of	22332

Sponsors and Collaborators

• Chong Kun Dang Pharmaceutical

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chong Kun Dang Pharmaceutical
• ClinicalTrials.gov Identifier: NCT02631954
• Other Study ID Numbers: 151HPS14014
• First Posted: Dec 16, 2015
• Last Update Posted: Mar 18, 2020
• Last Verified: Jan 1, 2016

• Additional relevant MeSH terms: Infections; Communicable Diseases; Mycoses; Candidiasis; Aspergillosis; Voriconazole

Study Results

Participant Flow

Pre-assignment Detail	Subjects who passed the screening were randomized using IWRS before conducting the clinical trail.

Arm/Group Title	TR Group	RT Group
Arm/Group Description	Test drug: Vorico Injection 200mg(Voriconazole) Wash out: 7 days Reference drug: Vfend® IV 200mg Vorico Injection 200mg(Voriconazole): Vorico Injection 200mg(Voriconazole) to administered intravenously once Vfend®(Voriconazole) IV 200mg: Vfend®(Voriconazole) IV 200mg to administered intravenously once	Reference drug: Vfend® IV 200mg Wash out: 7 days Test drug: Vorico Injection 200mg(Voriconazole) Vorico Injection 200mg(Voriconazole): Vorico Injection 200mg(Voriconazole) to administered intravenously once Vfend®(Voriconazole) IV 200mg: Vfend®(Voriconazole) IV 200mg to administered intravenously once
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	TR Group	RT Group	Total
Arm/Group Description	Test drug: Vorico Injection 200mg(Voriconazole) Wash out: 7 days Reference drug: Vfend® IV 200mg Vorico Injection 200mg(Voriconazole): Vorico Injection 200mg(Voriconazole) to administered intravenously once Vfend®(Voriconazole) IV 200mg: Vfend®(Voriconazole) IV 200mg to administered intravenously once	Reference drug: Vfend® IV 200mg Wash out: 7 days Test drug: Vorico Injection 200mg(Voriconazole) Vorico Injection 200mg(Voriconazole): Vorico Injection 200mg(Voriconazole) to administered intravenously once Vfend®(Voriconazole) IV 200mg: Vfend®(Voriconazole) IV 200mg to administered intravenously once	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	12 100%	24 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reference	Test
Arm/Group Description	Reference: Vfend® IV 200mg drug RT group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period I TR group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period II	Test: Vorico Injection 200mg(Voriconazole) drug RT group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period II TR group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period I
Measure Participants	23	23
Mean (Standard Deviation) [ng/mL]	2433.7 (2456.9)	1997.0 (406.2)

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reference	Test
Arm/Group Description	Reference: Vfend® IV 200mg drug RT group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period I TR group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period II	Test: Vorico Injection 200mg(Voriconazole) drug RT group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period II TR group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period I
Measure Participants	23	23
Mean (Standard Deviation) [hr*ng/mL]	6966.17 (2856.10)	7469.78 (3125.73)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reference	Test
Arm/Group Description	Reference: Vfend® IV 200mg drug RT group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period I TR group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period II	Test: Vorico Injection 200mg(Voriconazole) drug RT group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period II TR group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period I
Measure Participants	23	23
Mean (Standard Deviation) [hr]	1.57 (0.03)	1.58 (0.04)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reference	Test
Arm/Group Description	Reference: Vfend® IV 200mg drug RT group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period I TR group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period II	Test: Vorico Injection 200mg(Voriconazole) drug RT group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period II TR group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period I
Measure Participants	23	23
Mean (Standard Deviation) [hr*ng/mL]	8159.24 (4905.05)	8631.50 (4401.54)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reference	Test
Arm/Group Description	Reference: Vfend® IV 200mg drug RT group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period I TR group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period II	Test: Vorico Injection 200mg(Voriconazole) drug RT group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period II TR group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period I
Measure Participants	23	23
Mean (Standard Deviation) [Ratio]	0.94 (0.10)	0.90 (0.09)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reference	Test
Arm/Group Description	Reference: Vfend® IV 200mg drug RT group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period I TR group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period II	Test: Vorico Injection 200mg(Voriconazole) drug RT group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period II TR group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period I
Measure Participants	23	23
Mean (Standard Deviation) [1/hr]	0.10 (0.03)	0.10 (0.04)

7. Secondary Outcome

Title	t1/2
Description	The blood sampleing coleected from the subjects was analyzed and result was obtained.
Time Frame	0 , 0.5, 1, 1.25, 1.5, 1.58, 1.67, 1.83, 2, 2.5, 3, 4, 6, 8, 12, 24 hrs

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Reference	Test
Arm/Group Description	Reference: Vfend® IV 200mg drug RT group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period I TR group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period II	Test: Vorico Injection 200mg(Voriconazole) drug RT group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period II TR group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period I
Measure Participants	23	23
Mean (Standard Deviation) [hr]	8.42 (4.61)	7.98 (2.92)

Adverse Events

Time Frame	1 months
Adverse Event Reporting Description	There was no serious AE. A total of 58 AEs out of 24 subjects who took IP more than at least one time, were observed. All of the AEs were mild and recovered.
Arm/Group Title	Reference		Test
Arm/Group Description	Reference: Vfend® IV 200mg drug RT group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period I TR group: Vfend®(Voriconazole) IV 200mg to administered intravenously once at Period II		Test: Vorico Injection 200mg(Voriconazole) drug RT group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period II TR group: Vorico Injection 200mg(Voriconazole) to administered intravenously once at Period I
All Cause Mortality
	Reference		Test
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)
Serious Adverse Events
	Reference		Test
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Reference		Test
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/23 (91.3%)		22/24 (91.7%)
Eye disorders
photophobia	18/23 (78.3%)		21/24 (87.5%)
colour blindness acquired	1/23 (4.3%)		0/24 (0%)
vision blurred	2/23 (8.7%)		0/24 (0%)
visual impariment	1/23 (4.3%)		1/24 (4.2%)
Investigations
blood glucose increased	0/23 (0%)		1/24 (4.2%)
Lymphocyte count decreased	0/23 (0%)		1/24 (4.2%)
urine oxalate increased	0/23 (0%)		1/24 (4.2%)
white blood cells urine positive	1/23 (4.3%)		0/24 (0%)
Nervous system disorders
headache	0/23 (0%)		2/24 (8.3%)
Respiratory, thoracic and mediastinal disorders
nasal congestion	1/23 (4.3%)		0/24 (0%)
Vascular disorders
dizziness	3/23 (13%)		3/24 (12.5%)
epistaxis	1/23 (4.3%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.