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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00556998
First received: November 9, 2007
Last updated: February 27, 2012
Last verified: February 2012
Results First Received: August 2, 2010  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Pharmacokinetics
Intervention: Drug: Voriconazole

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
All Treatments Voriconazole intravenous (IV) loading dose (6 mg/kg) was administered in the morning and evening on Day 1, and the IV maintenance dose (4 mg/kg) was administered in the morning and evening on Days 2 to 7 (up to Day 20 if clinically indicated). The oral maintenance dosing regimen (300 mg every 12 hours or 150 mg every 12 hours if subject weighed less than 40 kg) was administered following voriconazole IV and lasted 6.5 days (up to Day 30 if clinically indicated).

Participant Flow for 2 periods

Period 1:   Voriconazole Intravenous (IV)
    All Treatments  
STARTED     26  
Treated     26  
COMPLETED     21 [1]
NOT COMPLETED     5  
Adverse Event                 1  
unspecified                 4  
[1] One participant received 2 days of oral; then received IV again before discontinuing from study.

Period 2:   Voriconazole Oral
    All Treatments  
STARTED     22 [1]
COMPLETED     20  
NOT COMPLETED     2  
Adverse Event                 1  
Intolerant of oral treatment                 1  
[1] One participant received voriconazole 150 mg every 12 hours during oral phase.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
All Treatments Voriconazole intravenous (IV) loading dose (6 mg/kg) was administered in the morning and evening on Day 1, and the IV maintenance dose (4 mg/kg) was administered in the morning and evening on Days 2 to 7 (up to Day 20 if clinically indicated). The oral maintenance dosing regimen (300 mg every 12 hours or 150 mg every 12 hours if subject weighed less than 40 kg) was administered following voriconazole IV and lasted 6.5 days (up to Day 30 if clinically indicated).

Baseline Measures
    All Treatments  
Number of Participants  
[units: participants]
  26  
Age, Customized  
[units: Years]
 
12     4  
13     10  
>13 to <17     12  
Gender, Customized  
[units: Participants]
 
Female     9  
Male     17  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   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.  Primary:   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.  Primary:   AUC12,ss Following Oral Administration   [ Time Frame: Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose ]

5.  Primary:   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.  Primary:   Tmax Following Oral Administration   [ Time Frame: Day 7 (up to Day 30) Predose, 1, 2, 4, 6, 8, and 12 hours postdose ]

7.  Secondary:   AUC12 Following IV Loading Dose   [ Time Frame: Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title AUC12 Following IV Loading Dose
Measure Description AUC12 = Area under the plasma concentration-time profile from time zero (predose) to twelve hours. AUC12 was obtained by the Linear/Log trapezoidal method.
Time Frame Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Reporting Groups
  Description
Voriconazole IV Voriconazole IV loading dose (6 mg/kg) in the morning and evening on Day 1.

Measured Values
    Voriconazole IV  
Number of Participants Analyzed  
[units: participants]
  22  
AUC12 Following IV Loading Dose  
[units: μg*h/mL]
Geometric Mean ± Standard Deviation
  9.14  ± 4.90  

No statistical analysis provided for AUC12 Following IV Loading Dose



8.  Secondary:   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 ]

9.  Secondary:   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 ]

10.  Secondary:   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 ]

11.  Secondary:   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 ]

12.  Secondary:   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 ]

13.  Secondary:   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 ]

14.  Secondary:   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 ]

15.  Secondary:   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 ]

16.  Secondary:   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 ]

17.  Other Pre-specified:   Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 IV Loading Dose.   [ Time Frame: Day 1 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

18.  Other Pre-specified:   Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 IV Steady State   [ Time Frame: Day 7 of IV dosing ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

19.  Other Pre-specified:   Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 Oral Dose All Subjects   [ Time Frame: Day 7 Oral dosing ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

20.  Other Pre-specified:   Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 Oral 300mg   [ Time Frame: Day 7 oral dosing ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

21.  Other Pre-specified:   Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax IV Loading Dose   [ Time Frame: Day 1 ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

22.  Other Pre-specified:   Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax IV Steady State   [ Time Frame: Day 7 of Intravenous dosing ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

23.  Other Pre-specified:   Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax Day 7 Oral All Participants   [ Time Frame: Day 7 of oral dosing ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

24.  Other Pre-specified:   Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax 300 mg Oral Dose   [ Time Frame: Day 7 of oral dosing ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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