Study Of The Pharmacokinetics And Safety Of Voriconazole In Children 2 To 11 Years Old Who Are At High Risk For Systemic Fungal Infection

An Open-Label, Intravenous To Oral Switch, Multiple Dose Study To Evaluate The Pharmacokinetics, Safety And Tolerability Of Voriconazole In Immunocompromised Children Aged 2 To <12 Years Who Are At High Risk For Systemic Fungal Infection

In this study we will measure the concentration of the drug called voriconazole which is used to fight infections caused by fungus in children who usually are cancer patients and have their immune system down. Since we know the dose in adults, and we think we know the matching doses in the young patients ages 2 to 12 years old, we will compare the amount of drug that goes into the system with what we know works in adults. We give the drug by a needle directly into the blood, then few days later we stop that and give the drug by mouth. Meanwhile, we draw a little bit of blood at certain times to measure the drug in it.

Study Overview

• Status: Completed
• Conditions: Candidemia; Candidiasis
• Intervention / Treatment: Drug: voriconazole (Vfend)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Pfizer Investigational Site
    • Tucson, Arizona, United States, 85724
      • Pfizer Investigational Site
  • California
    • Orange, California, United States, 92868
      • Pfizer Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Pfizer Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Pfizer Investigational Site
    • Atlanta, Georgia, United States, 30322-1062
      • Pfizer Investigational Site
    • Atlanta, Georgia, United States, 30342-1600
      • Pfizer Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Pfizer Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Pfizer Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Pfizer Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Pfizer Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Pfizer Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female from 2 to <12 years of age.
• Require treatment for the prevention of systemic fungal infection.
• Expected to develop neutropenia (ANC <500 cells/μL) lasting more than 10 days following chemotherapy.
• Anticipated to live for more than 3 months.

Exclusion Criteria:

• Evidence of any clinically significant liver or renal function or other abnormalities such as cardiac arrhythmia, hypokalemia, hypomagnesemia or hypocalcemia.
• Documented bacterial or viral infection not responding to appropriate treatment.
• Hypersensitivity to or severe intolerance of azole antifungal agents.
• Receiving other azoles or drugs that is are prohibited in the voriconazole label or associated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Children aged 2 to <12 years; Immunocompromised children aged 2 to <12 years who are at high risk for systemic fungal infection.

Drug: voriconazole (Vfend); Study Days 1 to 7: IV voriconazole 7 mg/kg q12h. Study Days 8 to 14: Oral voriconazole (POS) 200 mg q12h Notes: If unable to switch to oral medication on Day 8, subjects can continue with IV treatment up to Day 20 before switching to oral dose.; Only morning oral dose will be given on Day 14 (or the seventh day of oral dosing if IV regimen is extended). However, if clinically indicated, voriconazole treatment may be continued up to Day 30. (IV = Intravenous; POS = Powder for oral suspension); Other Names: UK-109,496; Vfend; voriconazole

What is the study measuring?

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 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose
Peak Plasma Concentration at Steady State (Cmax,ss) Following IV Administration		Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose
Time to Reach Cmax (Tmax) Following IV Administration		Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose
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 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose
Cmax,ss Following Oral Administration		Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose
Tmax Following Oral Administration		Day 7 (or later) 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 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose
Cmax Following an IV Loading Dose		Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose
Tmax Following an IV Loading Dose		Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose
Trough Concentrations (Cmin)		Day 7 (up to Day 20 or more) for IV; Day 7 (or later) 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.	Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose
Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration		Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose
Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration	Zero Tmax refers to the highest concentration observed for one participant at predose. The profile of the metabolite is relatively flat, which could result in slight variation in sample collection or assay process.	Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose
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.	Day 7 (or later) 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 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose
Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration		Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (ACTUAL): October 1, 2009
• Study Completion (ACTUAL): October 1, 2009

Study Registration Dates

• First Submitted: August 20, 2008
• First Submitted That Met QC Criteria: August 21, 2008
• First Posted (ESTIMATE): August 22, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): January 28, 2011
• Last Update Submitted That Met QC Criteria: January 26, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: Safety; Children; Pharmacokinetics; Voriconazole; Open-Label; Intravenous to oral switch; Immunocompromise; High Risk For Systemic Fungal Infection.
• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Invasive Fungal Infections; Fungemia; Candidiasis, Invasive; Infections; Candidiasis; Candidemia; Mycoses; 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: A1501088