Aspergillosis, Aspergilloma
Conditions
Keywords
Open-Label, Pharmacokinetics, Intravenous to oral switch, Safety, Voriconazole, Immunocompromise, Children, High Risk For Systemic Fungal Infection
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.
Interventions
DRUGVoriconazole
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)
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing | AUC12,ss was obtained by the Linear/Log trapezoidal method. |
| 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 | — |
| Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,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 | AUC12,ss was obtained by the Linear/Log trapezoidal method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | AUC12,ss was obtained by the Linear/Log trapezoidal method. |
| 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 | AUC12,ss was obtained by the Linear/Log trapezoidal method. |
| Maximum Observed Plasma Concentration at Steady State (Cmax,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 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) 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 | — |
| 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. | Ratio was calculated from the following formula; AUC12,ss Following Oral Administration over AUC12,ss Following IV Administration |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants Aged 2 to <12 Years Immunocompromised children aged 2 to \<12 years who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated). | 15 |
| Participants Aged 12 to<15 Years and Weighed <50 kg Immunocompromised children aged 12 to \<15 years and weighed less than 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (9 mg/kg on Day 1 and 8 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (9 mg/kg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated). | 4 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg Immunocompromised children aged 12 to \<15 years and weighed greater than or equal to 50 kg who are at high risk for systemic fungal infection. Voriconazole intravenous (IV) multiple dose (6 mg/kg on Day 1 and 4 mg/kg on Day 2 to 7 once every 12 hours) was administered in the morning and evening (up to Day 20 or more if clinically indicated). The oral dosing regimen (200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated). | 2 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Marketed voriconazole in post-therapy | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Participants Aged 2 to <12 Years | Participants Aged 12 to<15 Years and Weighed <50 kg | Participants Aged 12 to<15 Years and Weighed ≥50 kg | Total |
|---|---|---|---|---|
| Age, Continuous | 7.7 years STANDARD_DEVIATION 2.8 | 12.5 years STANDARD_DEVIATION 0.6 | 14.0 years STANDARD_DEVIATION 0 | 9.2 years STANDARD_DEVIATION 3.4 |
| Sex: Female, Male Female | 9 Participants | 2 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 1 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 15 | 4 / 4 | 1 / 2 |
| serious Total, serious adverse events | 0 / 15 | 0 / 4 | 0 / 2 |
Outcome results
Primary
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.
Time frame: 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
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following IV Administration | 51.92 μg*h/mL | Geometric Coefficient of Variation 51 |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following IV Administration | 83.39 μg*h/mL | Geometric Coefficient of Variation 56 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following IV Administration | 17.27 μg*h/mL | Geometric Coefficient of Variation 28 |
Primary
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.
Time frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following Oral Administration | 48.23 μg*h/mL | Geometric Coefficient of Variation 83 |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following Oral Administration | 59.42 μg*h/mL | Geometric Coefficient of Variation 67 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Area Under the Plasma Concentration-time Profile From Time Zero to Twelve Hours at Steady-State (AUC12,ss) Following Oral Administration | 10.00 μg*h/mL | — |
Primary
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following IV Administration
Time frame: 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
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following IV Administration | 7.753 mcg/mL | Geometric Coefficient of Variation 38 |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following IV Administration | 9.233 mcg/mL | Geometric Coefficient of Variation 55 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following IV Administration | 3.092 mcg/mL | Geometric Coefficient of Variation 42 |
Primary
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following Oral Administration
Time frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following Oral Administration | 7.755 mcg/mL | Geometric Coefficient of Variation 50 |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following Oral Administration | 7.910 mcg/mL | Geometric Coefficient of Variation 45 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) Following Oral Administration | 2.030 mcg/mL | — |
Primary
Number of Participants Assessed Color Vision Test
Time frame: 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
Population: The safety analysis was performed on all subjects who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Number of Participants Assessed Color Vision Test | Screening | 19 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Color Vision Test | The 7th day of IV treatment | 18 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Color Vision Test | The 1st day of oral treatment | 17 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Color Vision Test | The 7th day of oral treatment | 15 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Color Vision Test | The 30 day follow up visit | 14 participants |
Primary
Number of Participants Assessed Near Distance Visual Acuity Test
Time frame: 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
Population: The safety analysis was performed on all subjects who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Number of Participants Assessed Near Distance Visual Acuity Test | Screening | 18 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Near Distance Visual Acuity Test | The 7th day of IV treatment | 18 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Near Distance Visual Acuity Test | The 1st day of oral treatment | 17 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Near Distance Visual Acuity Test | The 7th day of oral treatment | 15 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Near Distance Visual Acuity Test | The 30 day follow up visit | 14 participants |
Primary
Number of Participants Assessed Visual Questionnaire
Time frame: 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
Population: The safety analysis was performed on all subjects who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Number of Participants Assessed Visual Questionnaire | The 7th day of IV treatment | 18 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Visual Questionnaire | Screening | 19 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Visual Questionnaire | The 1st day of oral treatment | 17 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Visual Questionnaire | The 7th day of oral treatment | 15 participants |
| Participants Aged 2 to <12 Years | Number of Participants Assessed Visual Questionnaire | The 30 day follow up visit | 14 participants |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following IV Administration
Time frame: 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
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Aged 2 to <12 Years | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following IV Administration | 2.96 hrs |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following IV Administration | 4.00 hrs |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following IV Administration | 1.34 hrs |
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Oral Administration
Time frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Aged 2 to <12 Years | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Oral Administration | 1.09 hrs |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Oral Administration | 1.00 hrs |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Oral Administration | 1.00 hrs |
Secondary
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
AUC12,ss was obtained by the Linear/Log trapezoidal method.
Time frame: 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
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants Aged 2 to <12 Years | 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 | 66.50 μg*h/mL | Geometric Coefficient of Variation 30 |
| Participants Aged 12 to<15 Years and Weighed <50 kg | 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 | 80.99 μg*h/mL | Geometric Coefficient of Variation 41 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | 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 | 40.00 μg*h/mL | Geometric Coefficient of Variation 2 |
Secondary
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
AUC12,ss was obtained by the Linear/Log trapezoidal method.
Time frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants Aged 2 to <12 Years | 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 | 79.86 μg*h/mL | Geometric Coefficient of Variation 36 |
| Participants Aged 12 to<15 Years and Weighed <50 kg | 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 | 90.84 μg*h/mL | Geometric Coefficient of Variation 19 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | 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 | 34.40 μg*h/mL | — |
Secondary
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration
Time frame: 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
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | 6.381 mcg/mL | Geometric Coefficient of Variation 28 |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | 8.066 mcg/mL | Geometric Coefficient of Variation 34 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | 3.835 mcg/mL | Geometric Coefficient of Variation 1 |
Secondary
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration
Time frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | 7.971 mcg/mL | Geometric Coefficient of Variation 31 |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | 8.912 mcg/mL | Geometric Coefficient of Variation 22 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | 3.720 mcg/mL | — |
Secondary
Ratio of AUC12,ss Following IV Administration Relative to AUC12,ss Following Oral Administration
Ratio was calculated from the following formula; AUC12,ss Following Oral Administration over AUC12,ss Following IV Administration
Time frame: 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.
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants Aged 2 to <12 Years | Ratio of AUC12,ss Following IV Administration Relative to AUC12,ss Following Oral Administration | 1.077 ratio | Standard Deviation 0.547 |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Ratio of AUC12,ss Following IV Administration Relative to AUC12,ss Following Oral Administration | 0.648 ratio | Standard Deviation 0.015 |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Ratio of AUC12,ss Following IV Administration Relative to AUC12,ss Following Oral Administration | 0.476 ratio | — |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration
Time frame: 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
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Aged 2 to <12 Years | Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | 5.05 hrs |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | 4.49 hrs |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration | 3.84 hrs |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration
Time frame: Day 14 (the 7th day of oral treatment) or later: predose, and 1, 2, 4, 6, 8, and 12 hours after dosing
Population: The pharmacokinetic parameter analysis was performed on all treated participants who had at least 1 of the pharmacokinetic parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Aged 2 to <12 Years | Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | 2.07 hrs |
| Participants Aged 12 to<15 Years and Weighed <50 kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | 2.03 hrs |
| Participants Aged 12 to<15 Years and Weighed ≥50 kg | Time to Reach Maximum Observed Plasma Concentration (Tmax) of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration | 3.80 hrs |