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

• ClinicalTrials.gov Identifier: NCT01383993
• Recruitment Status: Completed
• First Posted: June 28, 2011
• Results First Posted: May 9, 2014
• Last Update Posted: May 9, 2014
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: June 27, 2011
• First Posted Date: June 28, 2011
• Results First Submitted Date: April 7, 2014
• Results First Posted Date: May 9, 2014
• Last Update Posted Date: May 9, 2014
• Study Start Date: September 2011
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 8, 2014)

• Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following IV Administration [ Time Frame: Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion ]
  AUC12,ss was obtained by the Linear/Log trapezoidal method.
• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following IV Administration [ Time Frame: Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) Following IV Administration [ Time Frame: Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion ]
• Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following Oral Administration [ Time Frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing ]
  AUC12,ss was obtained by the Linear/Log trapezoidal method.
• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following Oral Administration [ Time Frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Oral Administration [ Time Frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing ]
• Number of Participants Assessed Near Distance Visual Acuity Test [ Time Frame: Screening, Day 7 (the 7th day of IV treatment), Day 8 (the 1st day of oral treatment), Day 14 (the 7th day of oral treatment), and the 30-day follow-up visit ]
• Number of Participants Assessed Color Vision Test [ Time Frame: Screening, Day 7 (the 7th day of IV treatment), Day 8 (the 1st day of oral treatment), Day 14 (the 7th day of oral treatment), and the 30-day follow-up visit ]
• Number of Participants Assessed Visual Questionnaire [ Time Frame: Screening, Day 7 (the 7th day of IV treatment), Day 8 (the 1st day of oral treatment), Day 14 (the 7th day of oral treatment), and the 30-day follow-up visit ]

Original Primary Outcome Measures (submitted: June 27, 2011)

• 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 ]
• 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 ]
• 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 ]
• AUC12,ss Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdos ]
• Cmax,ss Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdos ]
• Tmax Following Oral Administration [ Time Frame: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose ]

Current Secondary Outcome Measures (submitted: April 8, 2014)

• Ratio of AUC12,ss Following IV Administration Relative to AUC12,ss Following Oral Administration [ Time Frame: AUC12, ss for IV:Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion. AUC12,ss for oral: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing. ]
  Ratio was calculated from the following formula; AUC12,ss Following Oral Administration over AUC12,ss Following IV Administration
• Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration [ Time Frame: Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion ]
  AUC12,ss was obtained by the Linear/Log trapezoidal method.
• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration [ Time Frame: Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration [ Time Frame: Day 7 (up to Day 20): predose, 1 hour after the start of infusion, 10-20 minutes after the end of infusion, and 4, 6, 8, and 12 hours after the start of infusion ]
• Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration [ Time Frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing ]
  AUC12,ss was obtained by the Linear/Log trapezoidal method.
• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration [ Time Frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration [ Time Frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing ]

Original Secondary Outcome Measures (submitted: June 27, 2011)

• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Aspergillosis, Aspergilloma

Intervention

• 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
• 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

Study Arms

• 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.
  Intervention: Drug: 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.
  Intervention: Drug: Voriconazole

• Publications *: Mori M, Kobayashi R, Kato K, Maeda N, Fukushima K, Goto H, Inoue M, Muto C, Okayama A, Watanabe K, Liu P. Pharmacokinetics and safety of voriconazole intravenous-to-oral switch regimens in immunocompromised Japanese pediatric patients. Antimicrob Agents Chemother. 2015 Feb;59(2):1004-13. doi: 10.1128/AAC.04093-14. Epub 2014 Dec 1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 20, 2013): 21
• Original Estimated Enrollment (submitted: June 27, 2011): 20
• Actual Study Completion Date: May 2013
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 15 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT01383993
• Other Study ID Numbers: A1501096
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2014