Clinical trial NCT01383993: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Aspergillosis, Aspergilloma
Keywords: Open-Label
Pharmacokinetics
Intravenous to oral switch
Safety
Voriconazole
Immunocompromise
Children
High Risk For Systemic Fungal Infection
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-06-28
Enrollment: 21
Sex: ALL
Minimum age (years): 2
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following IV Administration
timeFrame: 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
measure: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following IV Administration
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) Following IV Administration
timeFrame: 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
measure: Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following Oral Administration
timeFrame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following Oral Administration
timeFrame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Oral Administration
timeFrame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: Number of Participants Assessed Near Distance Visual Acuity Test
timeFrame: 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
measure: Number of Participants Assessed Color Vision Test
timeFrame: 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
measure: Number of Participants Assessed Visual Questionnaire
timeFrame: 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
Secondary outcomes:
measure: Ratio of AUC12,ss Following IV Administration Relative to AUC12,ss Following Oral Administration
timeFrame: 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.
measure: 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
timeFrame: 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
measure: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration
timeFrame: 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
measure: 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
timeFrame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration
timeFrame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration
timeFrame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Japanese Red Cross Nagoya Daiichi Hospital
state: Aichi
city: Nagoya
country: Japan
facility: National hospital Organization Nagoya Medical Center
state: Aichi
city: Sapporo
country: Japan
facility: Sapporo Hokuyu Hosipital
state: Hokkaido
city: Yokohama
country: Japan
facility: Kanagawa Children's Medical Center
state: Kanagawa
city: Izumi
country: Japan
facility: Osaka Medical Center and Research Institute for Maternal and Child Health
state: Osaka
city: Shimotsuga-gun
country: Japan
facility: Dokkyo Medical University Hospital
state: Tochigi
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.