A Study Of The Safety, Tolerability And Effective Of Voriconazole For The Treatment Of Serious Candida Infection And Candida Infection Of The Throat In Pediatric Patients

A Prospective, Open-label, Non-comparative Study To Assess The Safety, Tolerability And Efficacy Of Voriconazole For The Primary And Salvage Treatment Of Invasive Candidiasis, Candidemia, And Esophageal Candidiasis In Pediatric Subjects

The purpose of this study is to determine whether voriconazole is safe and effective for the treatment of serious Candida infection and Candida infection of the esophagus in children and adolescents.

Study Overview

• Status: Terminated
• Conditions: Candidiasis
• Intervention / Treatment: Drug: voriconazole

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100045
    • Beijing Children's Hospital, Capital University of Medical Sciences
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
• Czech Republic
  • Brno, Czech Republic, 625 00
    • Fakultni nemocnice Brno - Klinika detske onkologie
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Department of Paediatrics and Adolescent Medicine
  • Shatin, N.T., Hong Kong
    • The Chinese University of Hong Kong, Prince of Wales Hospital
• Hungary
  • Budapest, Hungary, 1094
    • Semmelweis Egyetem, II. sz. Gyermekgyógyászati Klinika
  • Budapest, Hungary, 1097
    • Fovarosi Onkormanyzat Egyesitett Szent Istvan és Szent Laszlo Korhaz-Rendelointezet
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem, II. sz. Szemeszeti Klinika
• Mexico
  • DF
    • Colonia Insurgentes Cuicuilco, Delegacion Coyoacan, DF, Mexico, 04530
      • Instituto Nacional de Pediatría
• Philippines
  • Manila, Philippines, 1000
    • Rm. 112 ICHHD, National Institutes of Health-University of the Philippines Manila
  • Manila
    • Ermita,, Manila, Philippines, 1000
      • Medical Research Laboratory Philippine General Hospital University of the Philippines
• Poland
  • Olsztyn, Poland, 10-561
    • Oddzial Pediatryczny I- Hematologiczno-Onkologiczny
• Slovakia
  • Bratislava, Slovakia, 833 40
    • Detska Fakultna nemocnica s poliklinikou Bratislava

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female 2 to <18 years of age; Subjects 2 to <12 years of age will be permitted to enroll in this study only after a Pfizer sponsored pharmacokinetic study confirms the proposed dosage corresponding to this age group is appropriate.
• Patients with confirmed Candida infection of the blood, body tissues, or the esophagus.
• Patient's doctor feels voriconazole is an appropriate choice of therapy.

Exclusion Criteria:

• A known allergy to voriconazole or to azole to antifungal drugs.
• Females who are pregnant, lactating (breast feeding) or planning a pregnancy during the course of the study, or who are of childbearing potential and not using highly effective method of birth control.
• A patient who is receiving treatment with a drug know to interfere with the heart's electrical system (QTc prolongation).
• A patient who is receiving treatment with a drug that is not permitted to be used with voriconazole.
• For primary therapy: a patient who has received more than 48 hours of antifungal therapy for the current episode of Candida infection.
• A patient with significant underlying liver disease at the time of enrollment in the study.
• A patient with significant renal disease (CrCl < 50 ml/min) at the time of enrollment in the study.
• A patient with a high likelihood of death within 72 hours of study enrollment due to factors unrelated to Candida infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Active voriconazole; All subjects in this study will receive active voriconazole in an open-label fashion; there is no comparator in this study.

Drug: voriconazole; Subjects 12 - <18 yrs (excluding subjects 12 - 14 yrs weighing <50kg): For IC, the loading dose is 6 mg/kg IV q12h on Day 1, followed by 4 mg/kg IV q12h thereafter. Oral therapy, if given, will be administered at a dose of 200 mg q12h. For EC, no loading dose is required, and subjects will be initiated on 3 mg/kg IV q12h. Oral therapy, if given, will be administered at a dose of 200 mg q12h. Subjects 2 - <12 yrs, and subjects 12 - 14 weighing <50kg: For IC, the loading dose is 9 mg/kg IV q12h on Day 1, followed by 8 mg/kg IV q12h thereafter. For EC, no loading dose is required, and subjects will be initiated on 4 mg/kg IV q12. Oral therapy, if given, will be administered at a dose of 9 mg/kg q12h (maximum initial dose of 300 mg). Subjects will be treated for a minimum of 14 days for invasive candidiasis/candidemia or a minimum of 7 days for esophageal candidiasis. Subjects will be treated for up to a maximum of 42 days.; Other Names: Vfend

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events - Overall Summary	Percentage of participants with adverse events (AEs), serious adverse events (SAEs), severe AEs, who discontinued due to AEs, or who had dose redued or temporarily discontinued due to AEs.	Baseline up to 1 month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Global Response of Success at End of Treatment (EOT)	Global response was determined programmatically based on investigator assessment of clinical and microbiological response. Global response of success was defined as clinical cure or improvement AND microbiological eradication or presumed eradication. Exact 95 percent (%) confidence interval for binomial proportions using Clopper-Pearson method.	EOT (from 7 to 42 days of treatment)
All-Cause Mortality - Number of Participant Deaths		Day 28 and 1 Month Follow-up
Time to Death		Baseline up to 1 month follow-up

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Martin JM, Macias-Parra M, Mudry P, Conte U, Yan JL, Liu P, Capparella MR, Aram JA. Safety, Efficacy, and Exposure-Response of Voriconazole in Pediatric Patients With Invasive Aspergillosis, Invasive Candidiasis or Esophageal Candidiasis. Pediatr Infect Dis J. 2017 Jan;36(1):e1-e13. doi: 10.1097/INF.0000000000001339.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: March 10, 2010
• First Submitted That Met QC Criteria: March 23, 2010
• First Posted (Estimate): March 25, 2010

Study Record Updates

• Last Update Posted (Estimate): June 23, 2016
• Last Update Submitted That Met QC Criteria: May 17, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Invasive Candidiasis Candidemia Esophageal Candidiasis
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Candidiasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Voriconazole
• Other Study ID Numbers: A1501085; 2009-012848-16 (EudraCT Number)