Pharmacokinetics
Conditions
Keywords
pharmacokinetics and safety data of voriconazole in immunocompromised adolescents
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.
Interventions
DRUGVoriconazole
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.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve Over Dosing Interval at Steady State (AUC12,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 | 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. |
| Tmax Following Oral Administration | Day 7 (up to Day 30) 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 | — |
| AUC12,ss Following Oral Administration | 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. |
| 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 | — |
| 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC12,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 | 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. |
| 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 | — |
| 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 | 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. |
| 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 | — |
| AUC12 Following IV Loading Dose | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax 300 mg Oral Dose | 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. |
| Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 Oral 300mg | 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. |
| Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 Oral Dose All Subjects | 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. |
| Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 IV Steady State | 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. |
| Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax Day 7 Oral All Participants | 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. |
| Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - AUC12 IV Loading Dose. | 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. |
| Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax IV Steady State | 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. |
| Pharmacokinetic Parameters of Voriconazole in Adolescents Compared to Historical Adult Data - Cmax IV Loading Dose | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Voriconazole Intravenous (IV) | Adverse Event | 1 |
| Voriconazole Intravenous (IV) | Other | 4 |
| Voriconazole Oral | Adverse Event | 1 |
| Voriconazole Oral | Intolerant of oral treatment | 1 |
Baseline characteristics
| Characteristic | All Treatments |
|---|---|
| Age, Customized 12 | 4 Years |
| Age, Customized 13 | 10 Years |
| Age, Customized >13 to <17 | 12 Years |
| Sex/Gender, Customized Female | 9 Participants |
| Sex/Gender, Customized Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 26 | 22 / 22 |
| serious Total, serious adverse events | 4 / 26 | 4 / 22 |
Outcome results
Primary
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.
Time frame: Day 7 (up to Day 20) at predose, 40, 78 minutes, 4, 6, 8 and 12 hours after start of infusion
Population: Intent to treat (ITT) population of participants who had completed pharmacokinetic (PK) blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Voriconazole IV | Area Under the Curve Over Dosing Interval at Steady State (AUC12,ss) Following IV Administration | 22.39 μg*h/mL | Standard Deviation 21.47 |
Primary
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.
Time frame: Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Voriconazole IV | AUC12,ss Following Oral Administration | 16.74 μg*h/mL | Standard Deviation 13.5 |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Voriconazole IV | Cmax,ss Following Oral Administration | 2.35 μg/mL | Standard Deviation 1.41 |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Voriconazole IV | Peak Plasma Concentration at Steady State (Cmax,ss) Following IV Administration | 3.89 μg/mL | Standard Deviation 2.59 |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voriconazole IV | Time to Reach Cmax (Tmax) Following IV Administration | 1.30 hours |
Primary
Tmax Following Oral Administration
Time frame: Day 7 (up to Day 30) Predose, 1, 2, 4, 6, 8, and 12 hours postdose
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voriconazole IV | Tmax Following Oral Administration | 2.00 hours |
Secondary
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.
Time frame: Day 1 at predose, 60, 118 minutes, 4, 6, 8 and 12 hours after start of infusion
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Voriconazole IV | AUC12 Following IV Loading Dose | 9.14 μg*h/mL | Standard Deviation 4.9 |
Secondary
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.
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Voriconazole IV | AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | Day 1 | 21.18 μg*h/mL | Standard Deviation 6.8 |
| Voriconazole IV | AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | Day 7 (up to Day 20) | 36.21 μg*h/mL | Standard Deviation 9.2 |
Secondary
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.
Time frame: On Day 7 (up to Day 30) at predose, 1, 2, 4, 6, 8, and 12 hours postdose
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Voriconazole IV | AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | 44.07 μg*h/mL | Standard Deviation 13.86 |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Voriconazole IV | Cmax Following an IV Loading Dose | 2.25 μg/mL | Standard Deviation 0.86 |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Voriconazole IV | Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | Day 1 | 2.50 μg/mL | Standard Deviation 0.84 |
| Voriconazole IV | Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | Day 7 (up to Day 20) | 3.48 μg/mL | Standard Deviation 0.73 |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Voriconazole IV | Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | 4.44 μg/mL | Standard Deviation 1.43 |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data; n = number of participants who contributed to data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Voriconazole IV | Minimum Observed Plasma Trough Concentration (Cmin) | IV Day 7 (up to Day 20) (n=21) | 1.05 μg/mL | Standard Deviation 1.85 |
| Voriconazole IV | Minimum Observed Plasma Trough Concentration (Cmin) | Oral Day 7 (up to Day 30) (n=19) | 0.72 μg/mL | Standard Deviation 0.81 |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voriconazole IV | Tmax Following an IV Loading Dose | 1.97 hours |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Voriconazole IV | Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | Day 1 | 4.00 μg*h/mL |
| Voriconazole IV | Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | Day 7 (up to Day 20) | 4.03 μg*h/mL |
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
Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Voriconazole IV | Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | 5.97 hours |
Other Pre-specified
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.
Time frame: Day 1
Other Pre-specified
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.
Time frame: Day 7 of IV dosing
Other Pre-specified
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.
Time frame: Day 7 oral dosing
Other Pre-specified
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.
Time frame: Day 7 Oral dosing
Other Pre-specified
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.
Time frame: Day 7 of oral dosing
Other Pre-specified
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.
Time frame: Day 7 of oral dosing
Other Pre-specified
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.
Time frame: Day 1
Other Pre-specified
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.
Time frame: Day 7 of Intravenous dosing