Study Of The Pharmacokinetics And Safety Of Voriconazole In Children 2 To Less Than 15 Years Old Who Are At High Risk For Systemic Fungal Infection

Pfizer21 enrolled

Overview

In this study we will measure the concentration of the drug called voriconazole which is used to fight infections caused by fungus in children who usually are cancer patients and have their immune system down. Since we know the dose in adults, and we think we know the matching doses in the young patients ages 2 to less than 15 years old, we will compare the amount of drug that goes into the system with what we know works in adults. We give the drug by a needle directly into the blood, then few days later we stop that and give the drug by mouth. Meanwhile, we draw a little bit of blood at certain times to measure the drug in it.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Aspergillosis, Aspergilloma

Interventions

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)

VoriconazoleDRUG

Study Days 1: IV voriconazole 6 mg/kg q12h. Study Days 2 to 7: IV voriconazole 4 mg/kg q12h. Study Days 8 to 14: Oral voriconazole (POS) 200 mg q12h. 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)

Eligibility

Sex: ALLMin age: 2 YearsMax age: 15 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female from 2 to \<15 years of age. * Require treatment for the prevention of systemic fungal infection. * Expected to develop neutropenia (ANC \<500 cells/uL) lasting more than 10 days following chemotherapy. * Anticipated to live for more than 3 months. Exclusion Criteria: * Evidence of any clinically significant liver or renal function or other abnormalities such as cardiac arrhythmia, hypokalemia, hypomagnesemia or hypocalcemia. * Documented bacterial or viral infection not responding to appropriate treatment. * Hypersensitivity to or severe intolerance of azole antifungal agents. * Receiving other azoles or drugs that is are prohibited in the voriconazole label or associated.

Locations (6)

Japanese Red Cross Nagoya Daiichi Hospital

Nagoya, Aichi-ken, Japan

National hospital Organization Nagoya Medical Center

Nagoya, Aichi-ken, Japan

Sapporo Hokuyu Hosipital

Sapporo, Hokkaido, Japan

Kanagawa Children's Medical Center

Yokohama, Kanagawa, Japan

Osaka Medical Center and Research Institute for Maternal and Child Health

Izumi, Osaka, Japan

Dokkyo Medical University Hospital

Shimotsuga-gun, Tochigi, Japan

Outcomes

Primary Outcomes

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.

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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

Time frame: 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

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

Number of Participants Assessed Near Distance Visual Acuity Test

Time frame: 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

Number of Participants Assessed Color Vision Test

Time frame: 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

Number of Participants Assessed Visual Questionnaire

Time frame: 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

Secondary Outcomes

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

Time frame: 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.

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.

Time frame: 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) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration

Time frame: 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) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration

Time frame: 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) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration

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

Time frame: 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) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration

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

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