Voriconazole to Prevent Systemic Fungal Infections in Children
This study will examine how children's bodies metabolize and eliminate the anti-fungal drug voriconazole. The results will yield information needed to make recommendations for safe and effective dosing of the drug in children. Children with reduced immune function-such as those receiving drugs for cancer treatment-are at high risk for serious fungal infections.
Children between 2 and 12 years old who need treatment to prevent fungal infections may be eligible for this study. Candidates will be screened with a physical examination, eye examination, and blood and urine tests.
Children in the study will be hospitalized for 21 days. They will receive voriconazole twice a day (every 12 hours) for 8 days, infused through a vein over a period of 1 to 2 hours. The dose will be determined based on the individual child's weight. Blood samples will be collected at various intervals before and after the infusions on days 1, 2, 4 and 8 to determine the amount of drug in the blood. On day 8, the child will have another physical and eye examination, as well as additional blood and urine tests. If additional treatment is required, voriconazole may be continued for up to day 21. (Children who require the drug for more than 21 days may receive it under another research protocol.) On the last day of treatment, the child will have another physical examination, and blood and urine tests. These procedures will be repeated again at 30 to 35 days following the last dose of drug. A small sample of blood will also be analyzed for genetic information related to the rate of metabolism of voriconazole-that is, how fast or slow it is cleared (eliminated) by the liver.
Voriconazole is effective against several different fungi. It may protect children against serious fungal infections with fewer side effects than standard available therapy.
|Study Design:||Endpoint Classification: Safety Study
Primary Purpose: Treatment
|Official Title:||An Open Intravenous Multiple Dose, Multi-Center Study to Investigate the Pharmacokinetics, Safety and Toleration of Voriconazole in Children Aged 2-12 Years Who Require Treatment for the Prevention of Systemic Fungal Infection|
|Study Start Date:||June 2000|
|Estimated Study Completion Date:||January 2001|
The objective of this study is to evaluate the serum levels and pharmacokinetic parameters achieved following two dosage levels of voriconazole. In addition, the safety and toleration of intravenous voriconazole at two dosage levels in an immunocompromised pediatric patient population will be evaluated. Also, the plasma concentrations of the major metabolite of voriconazole (N-oxide) in these patients will be performed. The study is designed as a multi-center, open label multi-dose study of intravenous voriconazole. Intravenous voriconazole will be administered prophylactically twice daily to immunocompromised children at high risk for invasive mycoses. The patient population consists of children ages 2 years to 12 years of age; two age groups will be studied (2-<6, 6-12). Initial dosage levels will be 3mg/kg q12h and 4mg/kg q12h. The planned sample size is 24 children. For those children who do not complete the full 8 days of kinetics, a replacement patient will be added. Immunocompromised children at high risk for invasive mycoses will receive voriconazole prophylactically. Therapy will be initiated within 48 hours after completion of chemotherapy. Voriconazole therapy will continue until recovery from neutropenia. The first 12 children will initially receive a loading dose of 6mg/kg X 2 doses followed by 3mg/kg BID through day 4 of therapy. Twelve hour pharmacokinetics will be collected on day 4. Children will then receive 4mg/kg starting on the second dose of day 4 and will continue at that dosage level until recovery from neutropenia. Kinetics will again be collected at the 4mg/kg dosage level on day 8 of therapy. If the mean peak plasma concentration of voriconazole in the first 12 patients following 4mg/kg q12h dosing is less than 4,000ng/ml., the remaining 12 patients will receive voriconazole after day 4 at a dosage of 5mg/kg.
|United States, Maryland|
|National Cancer Institute (NCI)|
|Bethesda, Maryland, United States, 20892|