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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Aspergillosis, Aspergilloma	Drug: Voriconazole	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: September 2011
• Actual Primary Completion Date: May 2013
• Actual Study Completion Date: May 2013

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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 ]
3. 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 ]
4. 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.
5. 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 ]
6. 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 ]
7. 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 ]
8. 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 ]
9. 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 ]

Secondary Outcome Measures :

1. 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
2. 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.
3. 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 ]
4. 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 ]
5. 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.
6. 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 ]
7. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 15 Years (Child)
• Sexes Eligible for Study: All
• 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

Locations

Japan

Japanese Red Cross Nagoya Daiichi Hospital

Nagoya, Aichi, Japan

National hospital Organization Nagoya Medical Center

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:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01383993
• Other Study ID Numbers: A1501096
• First Posted: June 28, 2011
• Results First Posted: May 9, 2014
• Last Update Posted: May 9, 2014
• Last Verified: April 2014

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:

Infections; Mycoses; Aspergillosis; Bacterial Infections and Mycoses; Voriconazole; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP3A Inhibitors