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

NCT01383993 | Completed Phase 2 Results

• 1 other identifier: A1501096
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 6

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.

Conditions

Aspergillosis, Aspergilloma

Keywords

Open-Label; Pharmacokinetics; Intravenous to oral switch; Safety; Voriconazole; Immunocompromise; Children; High Risk For Systemic Fungal Infection

Outcome Measures

Primary Outcomes (9)

• Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following IV Administration

  AUC12,ss was obtained by the Linear/Log trapezoidal method.

  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

• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following IV Administration

  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

  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

  AUC12,ss was obtained by the Linear/Log trapezoidal method.

  Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing

• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following Oral Administration

  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

  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

  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

  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

  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 (7)

• Ratio of AUC12,ss Following IV Administration Relative to AUC12,ss Following Oral Administration

  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.

• 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

  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

• Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration

  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

  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

  Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing

Study Arms (2)

1.0

EXPERIMENTAL

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

2.0

EXPERIMENTAL

Immunocompromised children aged 12 to \<15 years weighing more than 50 kg who are at high risk for systemic fungal infection.

Drug: Voriconazole

Interventions

Voriconazole DRUG

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)

Also known as: UK-109,496; Vfend; Voriconazole

1.0

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (6)

Japanese Red Cross Nagoya Daiichi Hospital

Nagoya, Aichi-ken, Japan

Location

National hospital Organization Nagoya Medical Center

Nagoya, Aichi-ken, Japan

Location

Sapporo Hokuyu Hosipital

Sapporo, Hokkaido, Japan

Location

Kanagawa Children's Medical Center

Yokohama, Kanagawa, Japan

Location

Osaka Medical Center and Research Institute for Maternal and Child Health

Izumi, Osaka, Japan

Location

Dokkyo Medical University Hospital

Shimotsuga-gun, Tochigi, Japan

Location

Related Publications (1)

• 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.

  PMID: 25451051 DERIVED

Related Links

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

MeSH Terms

Conditions

Aspergillosis

Interventions

Voriconazole

Condition Hierarchy (Ancestors)

Mycoses; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2011
• First Posted: June 28, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: May 9, 2014
• Results First Posted: May 9, 2014

Record last verified: 2014-04

Locations

JP (6)