Study Of The Pharmacokinetics And Safety Of Voriconazole In Children 2 To 11 Years Old Who Are At High Risk For Systemic Fungal Infection

Study Overview
=================
Brief Summary
-----------------
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 12 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
-----------------
An Open-Label, Intravenous To Oral Switch, Multiple Dose Study To Evaluate The Pharmacokinetics, Safety And Tolerability Of Voriconazole In Immunocompromised Children Aged 2 To <12 Years Who Are At High Risk For Systemic Fungal Infection

Conditions
-----------------
Candidiasis, Candidemia

Intervention / Treatment
-----------------
* Drug: voriconazole (Vfend)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female from 2 to <12 years of age. Require treatment for the prevention of systemic fungal infection. Expected to develop neutropenia (ANC <500 cells/μL) 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
-----------------
Minimum Age: 2 Years
Maximum Age: 11 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Children aged 2 to <12 years<br>Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection. | Drug: voriconazole (Vfend)<br>* Study Days 1 to 7: IV voriconazole 7 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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve Over Dosing Interval at Steady State (AUC12,ss) Following IV Administration | AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method. | Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose | 
| Peak Plasma Concentration at Steady State (Cmax,ss) Following IV Administration |  | Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose | 
| Time to Reach Cmax (Tmax) Following IV Administration |  | Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose | 
| AUC12,ss Following Oral Administration | AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method. | Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose | 
| Cmax,ss Following Oral Administration |  | Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose | 
| Tmax Following Oral Administration |  | Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC12 Following IV Loading Dose | AUC12 = Area under the plasma concentration-time profile from time zero (predose) to twelve hours. AUC12 was obtained by the Linear/Log trapezoidal method. | Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose | 
| Cmax Following an IV Loading Dose |  | Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose | 
| Tmax Following an IV Loading Dose |  | Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose | 
| Trough Concentrations (Cmin) |  | Day 7 (up to Day 20 or more) for IV; Day 7 (or later) for oral at predose | 
| AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method. | Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose | 
| Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration |  | Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose | 
| Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | Zero Tmax refers to the highest concentration observed for one participant at predose. The profile of the metabolite is relatively flat, which could result in slight variation in sample collection or assay process. | Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose | 
| AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method. | Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose | 
| Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration |  | Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose | 
| Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration |  | Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose | 

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