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

• ClinicalTrials.gov Identifier: NCT00556998
• Recruitment Status: Completed
• First Posted: November 12, 2007
• Results First Posted: March 16, 2012
• Last Update Posted: May 5, 2016
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pharmacokinetics	Drug: Voriconazole	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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
• Study Start Date: June 2008
• Actual Primary Completion Date: December 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

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 Name: Vfend

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve Over Dosing Interval at Steady State (AUC12,ss) Following IV Administration [ Time Frame: Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion ]
   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.
2. Peak Plasma Concentration at Steady State (Cmax,ss) Following IV Administration [ Time Frame: Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion ]
3. Time to Reach Cmax (Tmax) Following IV Administration [ Time Frame: Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion ]
4. AUC12,ss Following Oral Administration [ Time Frame: Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose ]
   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.
5. Cmax,ss Following Oral Administration [ Time Frame: Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose ]
6. Tmax Following Oral Administration [ Time Frame: Day 7 (up to Day 30) Predose, 1, 2, 4, 6, 8, and 12 hours postdose ]

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 IV Loading Dose. [ Time Frame: Day 1 ]
   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.
2. Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 IV Steady State [ Time Frame: Day 7 of IV dosing ]
   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.
3. Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 Oral Dose All Subjects [ Time Frame: Day 7 Oral dosing ]
   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.
4. Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 Oral 300mg [ Time Frame: Day 7 oral dosing ]
   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.
5. Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax IV Loading Dose [ Time Frame: Day 1 ]
   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.
6. Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax IV Steady State [ Time Frame: Day 7 of Intravenous dosing ]
   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.
7. Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax Day 7 Oral All Participants [ Time Frame: Day 7 of oral dosing ]
   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.
8. Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax 300 mg Oral Dose [ Time Frame: Day 7 of oral dosing ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Illinois

Pfizer Investigational Site

Chicago, Illinois, United States, 60637

United States, Louisiana

Pfizer Investigational Site

New Orleans, Louisiana, United States, 70118

United States, North Carolina

Pfizer Investigational Site

Durham, North Carolina, United States, 27705

United States, Ohio

Pfizer Investigational Site

Cleveland, Ohio, United States, 44106

United States, Oregon

Pfizer Investigational Site

Portland, Oregon, United States, 97239

United States, Tennessee

Pfizer Investigational Site

Nashville, Tennessee, United States, 37232-2195

Pfizer Investigational Site

Nashville, Tennessee, United States, 37232

United States, Texas

Pfizer Investigational Site

Fort Worth, Texas, United States, 76104-2796

Pfizer Investigational Site

Houston, Texas, United States, 77030

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. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00556998
• Other Study ID Numbers: A1501081
• First Posted: November 12, 2007
• Results First Posted: March 16, 2012
• Last Update Posted: May 5, 2016
• Last Verified: March 2016

Keywords provided by Pfizer:

pharmacokinetics and safety data of voriconazole in immunocompromised adolescents

Additional relevant MeSH terms:

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