Study Of The Pharmacokinetics And Safety Of Voriconazole... | NCT01383993

Label	Type	Description	Intervention Names
1.0	Experimental	Immunocompromised children aged 2 to <15 and 12 to <15 years weighing <50 kg who are at high risk for systemic fungal infection.	Drug: Voriconazole
2.0	Experimental	Immunocompromised children aged 12 to <15 years weighing more than 50 kg who are at high risk for systemic fungal infection.	Drug: Voriconazole

Name	Type	Description	Arm Group Labels	Other Names
Voriconazole	Drug	Study Days 1: IV voriconazole 9 mg/kg q12h. Study Days 2 to 7: IV voriconazole 8 mg/kg q12h. Study Days 8 to 14: Oral voriconazole (POS) 9 mg/kg q12h with a maximum of 350 mg q12 h. Notes: If unable to switch to oral medication on Day 8, subjects can continue with IV treatment up to Day 20 before switching to oral dose. Only morning oral dose will be given on Day 14 (or the seventh day of oral dosing if IV regimen is extended). However, if clinically indicated, voriconazole treatment may be continued up to Day 30. (IV = Intravenous; POS = Powder for oral suspension)

Measure	Description	Time Frame
Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following IV Administration	AUC12,ss was obtained by the Linear/Log trapezoidal method.	Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following IV Administration		Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following IV Administration		Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion
Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following Oral Administration	AUC12,ss was obtained by the Linear/Log trapezoidal method.	Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following Oral Administration		Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Oral Administration		Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing

Measure	Description	Time Frame
Ratio of AUC12,ss Following IV Administration Relative to AUC12,ss Following Oral Administration	Ratio was calculated from the following formula; AUC12,ss Following Oral Administration over AUC12,ss Following IV Administration	AUC12, ss for IV:Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion. AUC12,ss for oral: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing.

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Japanese Red Cross Nagoya Daiichi Hospital		Nagoya	Aichi-ken		Japan
National hospital Organization Nagoya Medical Center

PubMed Identifier	Type	Citation	Retractions
25451051	Derived	Mori M, Kobayashi R, Kato K, Maeda N, Fukushima K, Goto H, Inoue M, Muto C, Okayama A, Watanabe K, Liu P. Pharmacokinetics and safety of voriconazole intravenous-to-oral switch regimens in immunocompromised Japanese pediatric patients. Antimicrob Agents Chemother. 2015 Feb;59(2):1004-13. doi: 10.1128/AAC.04093-14. Epub 2014 Dec 1.

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

ID	Title	Description
BG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
BG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
BG002	Participants Aged 12 to<15 Years and Weighed ≥50 kg	Immunocompromised children aged 12 to <15 years and weighed greater than or equal to 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (6 mg/kg on Day 1 and 4 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00015 BG0014 BG0022 BG00321

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following IV Administration

AUC12,ss was obtained by the Linear/Log trapezoidal method.

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg*h/mL

Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG002	Participants Aged 12 to<15 Years and Weighed ≥50 kg	Immunocompromised children aged 12 to <15 years and weighed greater than or equal to 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (6 mg/kg on Day 1 and 4 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Units	Counts
Participants	OG00014 OG0014 OG0022

Title

Denominators

Categories

Title	Measurements
	OG00051.92± 51 OG00183.39± 56 OG00217.27± 28

Primary

Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following IV Administration

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Primary

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following IV Administration

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Median

Full Range

hrs

Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Primary

Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following Oral Administration

AUC12,ss was obtained by the Linear/Log trapezoidal method.

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg*h/mL

Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Primary

Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following Oral Administration

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Primary

Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Oral Administration

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Median

Full Range

hrs

Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Primary

Number of Participants Assessed Near Distance Visual Acuity Test

The safety analysis was performed on all subjects who received at least 1 dose of study medication.

Posted

Number

participants

Screening, Day 7 (the 7th day of IV treatment), Day 8 (the 1st day of oral treatment), Day 14 (the 7th day of oral treatment), and the 30-day follow-up visit

ID	Title	Description
OG000	All Participants	Immunocompromised children aged 2 to <15 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg or 6 mg/kg on Day 1 and 8 mg/kg or 4 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg or 200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Units	Counts
Participants	OG000

Primary

Number of Participants Assessed Color Vision Test

The safety analysis was performed on all subjects who received at least 1 dose of study medication.

Posted

Number

participants

Screening, Day 7 (the 7th day of IV treatment), Day 8 (the 1st day of oral treatment), Day 14 (the 7th day of oral treatment), and the 30-day follow-up visit

ID	Title	Description
OG000	All Participants	Immunocompromised children aged 2 to <15 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg or 6 mg/kg on Day 1 and 8 mg/kg or 4 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg or 200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Units	Counts
Participants	OG000

Primary

Number of Participants Assessed Visual Questionnaire

The safety analysis was performed on all subjects who received at least 1 dose of study medication.

Posted

Number

participants

Screening, Day 7 (the 7th day of IV treatment), Day 8 (the 1st day of oral treatment), Day 14 (the 7th day of oral treatment), and the 30-day follow-up visit

ID	Title	Description
OG000	All Participants	Immunocompromised children aged 2 to <15 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg or 6 mg/kg on Day 1 and 8 mg/kg or 4 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg or 200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Units	Counts
Participants	OG000

Secondary

Ratio of AUC12,ss Following IV Administration Relative to AUC12,ss Following Oral Administration

Ratio was calculated from the following formula; AUC12,ss Following Oral Administration over AUC12,ss Following IV Administration

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Mean

Standard Deviation

ratio

AUC12, ss for IV:Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion. AUC12,ss for oral: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing.

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Secondary

Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration

AUC12,ss was obtained by the Linear/Log trapezoidal method.

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg*h/mL

Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Secondary

Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Median

Full Range

hrs

Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Secondary

Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration

AUC12,ss was obtained by the Linear/Log trapezoidal method.

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg*h/mL

Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Secondary

Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration

The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.

Posted

Median

Full Range

hrs

Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing

ID	Title	Description
OG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
OG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 16.0	Systematic Assessment	EG00010 affected15 at risk EG0012 affected4 at risk EG0021 affected2 at risk
Histiocytosis haematophagic	Blood and lymphatic system disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Colour blindness	Congenital, familial and genetic disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Chromatopsia	Eye disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Conjunctivitis	Eye disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Keratitis	Eye disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Photophobia	Eye disorders	MedDRA 16.0	Systematic Assessment	EG0005 affected15 at risk EG0013 affected4 at risk EG0021 affected2 at risk
Vision blurred	Eye disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Anorectal disorder	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0010 affected4 at risk EG0021 affected2 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Lip dry	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Painful defaecation	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Toothache	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Vomiting	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Catheter site pain	General disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Pyrexia	General disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Cystitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Pneumonia	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Sepsis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Alanine aminotransferase increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0012 affected4 at risk EG0020 affected2 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0012 affected4 at risk EG0020 affected2 at risk
Blood bilirubin increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Blood potassium decreased	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Blood pressure increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Blood urine present	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Liver function test abnormal	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Weight decreased	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Headache	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0002 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0001 affected15 at risk EG0010 affected4 at risk EG0020 affected2 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0003 affected15 at risk EG0010 affected4 at risk EG0021 affected2 at risk
Hyperaemia	Vascular disorders	MedDRA 16.0	Systematic Assessment	EG0000 affected15 at risk EG0011 affected4 at risk EG0020 affected2 at risk

ID	Term
D009181	Mycoses
D001423	Bacterial Infections and Mycoses
D007239	Infections

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Participants Aged 2 to <12 Years	Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).	15	13	15
EG001	Participants Aged 12 to<15 Years and Weighed <50 kg	Immunocompromised children aged 12 to <15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).	4	4	4
EG002	Participants Aged 12 to<15 Years and Weighed ≥50 kg	Immunocompromised children aged 12 to <15 years and weighed greater than or equal to 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (6 mg/kg on Day 1 and 4 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).	2	1	2