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
N/A
N/A
Both
Aspergillosis, Candidiasis, Fungal Diseases, Mycoses
Trial Information
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
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.
Inclusion Criteria
Children (male or female) ages 2-12 years who require treatment for the prevention of
systemic fungal infection.
Children who are expected to develop neutropenia lasting for more than 10 days following
chemotherapy for one of the following conditions: leukemia, lymphoma, aplastic anemia, or
as the preparative regimen for bone marrow transplantation.
Patients who are anticipated to live more than 3 months.
Females of child-bearing potential (post-menarchal) must have a negative pregnancy test at
entry.
Informed consent of the parent or legally authorized representative obtained prior to
entry.
Assent will be obtained from minors capable of understanding.
No patients who are receiving and cannot discontinue the following drugs at least 24 hours
prior to study start: terfenadine and cisapride (due to the possibility of QTc
prolongation). Omegprazole (an inhibitor of CYP2C19) which is known to increase plasma
voriconazole levels.
No patients who have received the following drugs within 14 days prior to study entry:
rifampicin, rifabutin, carbamazepine, phenytoin, nevirapine and barbiturates as these are
potent inducers of hepatic enzymes and will result in undetectable levels of voriconazole.
No patients who have received astemizole within the previous 60 days.
No patients who are taking or are likely to receive any investigational drugs except:
used for cancer treatment, antiretroviral agents, and drugs used for treatments of any
AIDS defining opportunistic infections.
No patients with a history or hypersensitivity to or severe intolerance of azole
antifungal agents.
No patients who have already been entered onto this protocol once.
No patient with medical history or evidence of cardiac arrhythmia.
No patients with AST and ALT greater than or equal to 5XULN.
No patients with moderate and severe renal impairment (i.e., calculated creatine clearance
less than 30ml/min). If creatinine clearance is reduced to less than 30 ml/min at any
time during the study, the patient must be discontinued from the study. Creatine
clearance will be calculated using the following equation: 0.55 X height (cm)/serum
creatinine (mg/dL).
Any other condition which, in the opinion of the investigator, would make the patient
unsuitable for enrollment.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Primary Purpose: Treatment
Authority:
United States: Federal Government
Study ID:
000150
NCT ID:
NCT00005912
Start Date:
June 2000
Completion Date:
January 2001
Related Keywords:
- Aspergillosis
- Candidiasis
- Fungal Diseases
- Mycoses
- Aspergillosis
- Candidiasis
- Fungal Infections
- Fungemia
- Prophylactic Antifungal Therapy
- Pediatric Fungal Infection
- Aspergillosis
- Candidiasis
- Mycoses
Name | Location |
|---|---|
| National Cancer Institute (NCI) | Bethesda, Maryland 20892 |
