A Multiple-Dose Study To Evaluate The Pharmacokinetics And Safety Of Voriconazole In Immunocompromised Adolescents

An Open-Label, Intravenous To Oral Switch, Multiple Dose Study To Evaluate The Pharmacokinetics, Safety And Tolerability Of Voriconazole In Immunocompromised Adolescents Aged 12 To <17 Years Who Are At High Risk For Systemic Fungal Infection

This study is designed to collect additional pharmacokinetic and safety data of voriconazole in immunocompromised adolescents receiving intravenous and oral voriconazole. This will help establish voriconazole dosing recommendations for adolescents.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: Voriconazole

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Pfizer Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Pfizer Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Pfizer Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Pfizer Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Pfizer Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37232-2195
      • Pfizer Investigational Site
  • Texas
    • Fort Worth, Texas, United States, 76104-2796
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77030
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who are expected to develop neutropenia following chemotherapy.
• Subjects who require treatment for the prevention of systemic fungal infection.

Exclusion Criteria:

• Subjects with a history of severe intolerance of azole antifungal agents.
• Subjects with documented bacterial or viral infection at the time of study entry who are not responding to appropriate treatment against the infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Voriconazole; Voriconazole will be used for prophylaxis purpose. 6 mg/kg IV q12h on the first day (Day 1) and 4 mg/kg IV q12h for at least 5.5 days. The IV treatment is no more than 20 days. Then switch to 300 mg oral tablets q12h for at least 6.5 days. The total treatment duration is no more than 30 days.; Other Names: Vfend

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. AUC12,ss was obtained by the Linear/Log trapezoidal method.	Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion
Peak Plasma Concentration at Steady State (Cmax,ss) Following IV Administration		Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion
Time to Reach Cmax (Tmax) Following IV Administration		Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion
AUC12,ss Following Oral Administration	AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.	Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose
Cmax,ss Following Oral Administration		Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose
Tmax Following Oral Administration		Day 7 (up to Day 30) Predose, 1, 2, 4, 6, 8, and 12 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC12 Following IV Loading Dose	AUC12 = Area under the plasma concentration-time profile from time zero (predose) to twelve hours. AUC12 was obtained by the Linear/Log trapezoidal method.	Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion
Tmax Following an IV Loading Dose		Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion
Cmax Following an IV Loading Dose		Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion
Minimum Observed Plasma Trough Concentration (Cmin)		Day 7 (up to Day 20) for IV; Day 7 (up to Day 30) for oral at predose
AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration	AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.	Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion and on Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6 8 and 12 hours after start of infusion
Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration		Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion and on Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6 8 and 12 hours after start of infusion
Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration		Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion and on Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6 8 and 12 hours after start of infusion
AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration	AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.	On Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose
Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration		Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose
Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration		Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 IV Loading Dose.	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 1
Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 IV Steady State	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 7 of IV dosing
Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 Oral Dose All Subjects	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 7 Oral dosing
Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 Oral 300mg	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 7 oral dosing
Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax IV Loading Dose	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 1
Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax IV Steady State	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 7 of Intravenous dosing
Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax Day 7 Oral All Participants	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 7 of oral dosing
Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax 300 mg Oral Dose	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 7 of oral dosing

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 9, 2007
• First Submitted That Met QC Criteria: November 9, 2007
• First Posted (Estimate): November 12, 2007

Study Record Updates

• Last Update Posted (Estimate): May 5, 2016
• Last Update Submitted That Met QC Criteria: March 31, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: pharmacokinetics and safety data of voriconazole in immunocompromised adolescents
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Voriconazole
• Other Study ID Numbers: A1501081