Study Of The Pharmacokinetics And Safety Of Voriconazole In Children 2 To Less Than 15 Years Old Who Are At High Risk For Systemic Fungal Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01383993
First received: June 27, 2011
Last updated: May 20, 2013
Last verified: May 2013
  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 less than 15 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
Aspergillosis, Aspergilloma
Drug: Voriconazole
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: An Open-Label, Non-Controlled, Multicenter, Intravenous To Oral Switch, Phase 2 Study To Evaluate The Pharmacokinetics, Safety And Tolerability Of Voriconazole In Immunocompromised Children Aged 2 To Less Than 15 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 AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. [ Time Frame: Day 7 (up to Day 20 or more) at predose, 60 and 162 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • 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 162 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 162 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 postdos ] [ Designated as safety issue: No ]
  • Cmax,ss Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdos ] [ 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:
  • Ratio of AUC12,ss Following IV Administration and AUC12,ss Following Oral Administration [ Time Frame: Day 7 (up to Day 20 or more) at predose, 60 and 162 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration [ Time Frame: Day 7 (up to Day 20 or more) at predose, 60 and 162 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration [ Time Frame: Day 7 (up to Day 20 or more) at predose, 60 and 162 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: Day 7 (up to Day 20 or more) at predose, 60 and 162 minutes, 4, 6, 8 and 12 hours postdose ] [ Designated as safety issue: No ]
  • 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 ]
  • 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: 21
Study Start Date: September 2011
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1.0
Immunocompromised children aged 2 to <15 and 12 to <15 years weighing <50 kg who are at high risk for systemic fungal infection.
Drug: Voriconazole

Study Days 1: IV voriconazole 9 mg/kg q12h. Study Days 2 to 7: IV voriconazole 8 mg/kg q12h. Study Days 8 to 14: Oral voriconazole (POS) 9 mg/kg q12h with a maximum of 350 mg q12 h.

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 Name: UK-109,496; Vfend; Voriconazole
Experimental: 2.0
Immunocompromised children aged 12 to <15 years weighing more than 50 kg who are at high risk for systemic fungal infection.
Drug: Voriconazole

Study Days 1: IV voriconazole 6 mg/kg q12h. Study Days 2 to 7: IV voriconazole 4 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 Name: UK-109,496; Vfend; Voriconazole

  Eligibility

Ages Eligible for Study:   2 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female from 2 to <15 years of age.
  • Require treatment for the prevention of systemic fungal infection.
  • Expected to develop neutropenia (ANC <500 cells/uL) 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: NCT01383993

Locations
Japan
National hospital Organization Nagoya Medical Center
Nagoya, Aichi, Japan
Japanese Red Cross Nagoya Daiichi Hospital
Nagoya, Aichi, Japan
Sapporo Hokuyu Hosipital
Sapporo, Hokkaido, Japan
Kanagawa Children's Medical Center
Yokohama, Kanagawa, Japan
Osaka Medical Center and Research Institute for Maternal and Child Health
Izumi, Osaka, Japan
Dokkyo Medical University Hospital
Shimotsuga-gun, Tochigi, Japan
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01383993     History of Changes
Other Study ID Numbers: A1501096
Study First Received: June 27, 2011
Last Updated: May 20, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

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:
Aspergillosis
Mycoses
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 23, 2014