A Multiple-Dose Study To Evaluate The Pharmacokinetics And Safety Of Voriconazole In Immunocompromised Adolescents

Study Overview
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Brief Summary
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This study is designed to collect additional pharmacokinetic and safety data of voriconazole in immunocompromised adolescents receiving intravenous and oral voriconazole. This will help establish voriconazole dosing recommendations for adolescents.

Official Title
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An Open-Label, Intravenous To Oral Switch, Multiple Dose Study To Evaluate The Pharmacokinetics, Safety And Tolerability Of Voriconazole In Immunocompromised Adolescents Aged 12 To <17 Years Who Are At High Risk For Systemic Fungal Infection

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: Voriconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are expected to develop neutropenia following chemotherapy. Subjects who require treatment for the prevention of systemic fungal infection. Exclusion Criteria: Subjects with a history of severe intolerance of azole antifungal agents. Subjects with documented bacterial or viral infection at the time of study entry who are not responding to appropriate treatment against the infection.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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<br> | Drug: Voriconazole<br>* Voriconazole will be used for prophylaxis purpose. 6 mg/kg IV q12h on the first day (Day 1) and 4 mg/kg IV q12h for at least 5.5 days. The IV treatment is no more than 20 days. Then switch to 300 mg oral tablets q12h for at least 6.5 days. The total treatment duration is no more than 30 days.<br>* Other names: Vfend;|

What is the study measuring?
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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) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion | 
| Peak Plasma Concentration at Steady State (Cmax,ss) Following IV Administration |  | Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion | 
| Time to Reach Cmax (Tmax) Following IV Administration |  | Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion | 
| 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 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose | 
| Cmax,ss Following Oral Administration |  | Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose | 
| Tmax Following Oral Administration |  | Day 7 (up to Day 30) 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 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion | 
| Tmax Following an IV Loading Dose |  | Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion | 
| Cmax Following an IV Loading Dose |  | Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion | 
| Minimum Observed Plasma Trough Concentration (Cmin) |  | Day 7 (up to Day 20) for IV; Day 7 (up to Day 30) 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. | Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion and on Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6 8 and 12 hours after start of infusion | 
| Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration |  | Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion and on Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6 8 and 12 hours after start of infusion | 
| Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration |  | Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion and on Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6 8 and 12 hours after start of infusion | 
| 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. | On Day 7 (up to Day 30) at 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 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose | 
| Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration |  | Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics and safety data of voriconazole in immunocompromised adolescents