A Study to Investigate the Pharmacokinetics, Safety and Tolerability of Voriconazole in Childre

• Conditions: Systemic fungal infection; MedDRA version: 18.0Level: LLTClassification code 10042941Term: Systemic fungal infection NOSSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2014-004184-21-Outside-EU/EEA
• Lead Sponsor: Pfizer, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05-21
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1.Subjects (both male and female) from 2 to less than (<)12 years of age who require treatment for the prevention of systemic fungal infection, and who can tolerate being switched to oral therapy between Days 8 and 12.
2.Subjects who are expected to develop neutropenia (absolute neutrophil count [ANC < 500/microliter [µl]) lasting more than 10 days following chemotherapy for one of the following conditions:
a.Leukemia, including ALL, AML and relapsed leukemia
b.Lymphoma, including relapsed lymphoma
c.Aplastic anemia
d.As the preparative regimen for bone marrow or stem cell transplantation
3. Subjects who are anticipated to live for more than 3 months
Are the trial subjects under 18? yes
Number of subjects for this age range: 48
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Subjects who are receiving and cannot discontinue the following drugs at least 24 hours prior to study start, or, if they need to commence any of the following during the study:
a.Terfenadine, pimozide, quinidine, astemizole and cisapride (due to the possibility of QTc prolongation)
b.Omeprazole (an inhibitor of cytochrome P450 2C19 [CYP2C19] which is known to increase plasma voriconazole levels)
c.Ergot alkaloids
2.Subjects who have received the following drugs within 14 days
prior to study entry:
Rifampicin, rifampin, rifabutin, carbamazepine, phenytoin, nevirapine and long acting barbiturates as these are inducers of hepatic enzymes and may result in undetectable levels of voriconazole.
a.Sirolimus as voriconazole is known to increase significantly sirolimus blood levels.
3.Subjects with any clinically significant abnormality following review of screening laboratory data other than that associated with their underlying disease.
4.Liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT] or total bilirubin) > 5 * upper limit of normal [ULN].
5.In subjects with clinically relevant hypokalemia potassium needs to be corrected before initiation of study treatment.
6.Subjects who are taking, or are likely to receive, any investigational drug other than chemotherapy, antiretroviral agents, and drugs used for the treatments of AIDS defining opportunistic infections, all of which are allowed.
7.Subjects with a history of hypersensitivity to or severe intolerance of azole antifungal agents.
8.Subjects who have already been entered into this protocol Subjects with moderate and severe renal impairment (i.e., calculated creatinine clearance <30 milliliter per minute (ml/min). Creatinine clearance will be calculated using the equation:
Creatinine Clearance (ml/min) = 0.55*height (centimeter [cm])/serum creatinine (milligram per deciliter [mg/dL])
9. Subjects who have prior or current evidence of cardiac
arrhythmia.
10. Females of child-bearing potential.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the pharmacokinetics of voriconazole following intravenous to oral switch in children aged 2 to less than (<) 12 years.<br>;Secondary Objective: To evaluate the safety and tolerability of multiple dose administration of voriconazole in children requiring treatment for the prevention of systemic fungal infection.<br>;Primary end point(s): 1. Area Under the Curve from Time Zero to end of dosing interval (AUCtau).<br>2. Maximum Observed Plasma Concentration (Cmax).<br>3. Time to Reach Maximum Observed Plasma Concentration (Tmax). <br>4. Bioavailability (F);Timepoint(s) of evaluation of this end point: 1. 2min pre-infusion end and 4, 6, 8 and 12hour (h) post-infusion start on day 4 and day 12.<br>2. 2min pre-infusion end and 4, 6, 8 and 12h post-infusion start on day 4 and day 12.<br>3. 2min pre-infusion end and 4, 6, 8 and 12h post-infusion start on day 4 and day 12.<br>4. 2min pre-infusion end and 4, 6, 8 and 12h post-infusion start on day 4 anad day 12.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs);Timepoint(s) of evaluation of this end point: Up to day 12