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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00739934
First received: August 20, 2008
Last updated: January 26, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Candidiasis
Candidemia
Drug: voriconazole (Vfend)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Area Under the Curve Over Dosing Interval at Steady State (AUC12,ss) Following IV Administration [ Time Frame: Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Peak Plasma Concentration at Steady State (Cmax,ss) Following IV Administration [ Time Frame: Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • Time to Reach Cmax (Tmax) Following IV Administration [ Time Frame: Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • AUC12,ss Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Cmax,ss Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • Tmax Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • AUC12 Following IV Loading Dose [ Time Frame: Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
    AUC12 = Area under the plasma concentration-time profile from time zero (predose) to twelve hours. AUC12 was obtained by the Linear/Log trapezoidal method.

  • Cmax Following an IV Loading Dose [ Time Frame: Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • Tmax Following an IV Loading Dose [ Time Frame: Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • Trough Concentrations (Cmin) [ Time Frame: Day 7 (up to Day 20 or more) for IV; Day 7 (or later) for oral at predose ] [ Designated as safety issue: No ]
  • AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration [ Time Frame: Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration [ Time Frame: Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration [ Time Frame: Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
    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.

  • Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: December 2008
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:

  1. 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.
  2. 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 Name: UK-109,496; Vfend; voriconazole

  Eligibility

Ages Eligible for Study:   2 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00739934

Locations
United States, Arizona
Pfizer Investigational Site
Tucson, Arizona, United States, 85719
Pfizer Investigational Site
Tucson, Arizona, United States, 85724
United States, California
Pfizer Investigational Site
Orange, California, United States, 92868
United States, Florida
Pfizer Investigational Site
Jacksonville, Florida, United States, 32207
United States, Georgia
Pfizer Investigational Site
Atlanta, Georgia, United States, 30322
Pfizer Investigational Site
Atlanta, Georgia, United States, 30322-1062
Pfizer Investigational Site
Atlanta, Georgia, United States, 30342-1600
United States, Louisiana
Pfizer Investigational Site
New Orleans, Louisiana, United States, 70118
United States, Maryland
Pfizer Investigational Site
Baltimore, Maryland, United States, 21215
United States, North Carolina
Pfizer Investigational Site
Durham, North Carolina, United States, 27710
United States, Ohio
Pfizer Investigational Site
Cleveland, Ohio, United States, 44106
United States, Oregon
Pfizer Investigational Site
Portland, Oregon, United States, 97239
United States, Tennessee
Pfizer Investigational Site
Nashville, Tennessee, United States, 37232
United States, Texas
Pfizer Investigational Site
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00739934     History of Changes
Other Study ID Numbers: A1501088
Study First Received: August 20, 2008
Results First Received: September 17, 2010
Last Updated: January 26, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Open-Label
Pharmacokinetics
Intravenous to oral switch
Safety
Voriconazole
Immunocompromise
Children
High Risk For Systemic Fungal Infection.

Additional relevant MeSH terms:
Candidiasis
Mycoses
Candidemia
Fungemia
Sepsis
Infection
Candidiasis, Invasive
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Voriconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014