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

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label, Non-Controlled, Multicenter, Intravenous To Oral Switch, Phase 2 Study To Evaluate The Pharmacokinetics, Safety And Tolerability Of Voriconazole In Immunocompromised Children Aged 2 To Less Than 15 Years Who Are At High Risk For Systemic Fungal Infection

Conditions
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Aspergillosis, Aspergilloma

Intervention / Treatment
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* Drug: Voriconazole
* Drug: Voriconazole


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.0<br>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<br>* 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)<br>* Other names: UK-109,496; Vfend; Voriconazole;|
| Experimental: 2.0<br>Immunocompromised children aged 12 to <15 years weighing more than 50 kg who are at high risk for systemic fungal infection. | Drug: Voriconazole<br>* 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)<br>* Other names: UK-109,496; Vfend; Voriconazole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 
| Number of Participants Assessed Near Distance Visual Acuity Test |  | 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 |  | 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 |  | 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 Outcome Measures

| Outcome Measure | 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. | 
| 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. | 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 |  | 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 |  | 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. | 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 |  | 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) of N-oxide Voriconazole Metabolite (UK-121, 265) 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open-Label, Pharmacokinetics, Intravenous to oral switch, Safety, Voriconazole, Immunocompromise, Children, High Risk For Systemic Fungal Infection