Candidiasis
Conditions
Keywords
Invasive Candidiasis Candidemia Esophageal Candidiasis
Brief summary
The purpose of this study is to determine whether voriconazole is safe and effective for the treatment of serious Candida infection and Candida infection of the esophagus in children and adolescents.
Interventions
DRUGvoriconazole
Subjects 12 - \<18 yrs (excluding subjects 12 - 14 yrs weighing \<50kg): For IC, the loading dose is 6 mg/kg IV q12h on Day 1, followed by 4 mg/kg IV q12h thereafter. Oral therapy, if given, will be administered at a dose of 200 mg q12h. For EC, no loading dose is required, and subjects will be initiated on 3 mg/kg IV q12h. Oral therapy, if given, will be administered at a dose of 200 mg q12h. Subjects 2 - \<12 yrs, and subjects 12 - 14 weighing \<50kg: For IC, the loading dose is 9 mg/kg IV q12h on Day 1, followed by 8 mg/kg IV q12h thereafter. For EC, no loading dose is required, and subjects will be initiated on 4 mg/kg IV q12. Oral therapy, if given, will be administered at a dose of 9 mg/kg q12h (maximum initial dose of 300 mg). Subjects will be treated for a minimum of 14 days for invasive candidiasis/candidemia or a minimum of 7 days for esophageal candidiasis. Subjects will be treated for up to a maximum of 42 days.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female 2 to \<18 years of age; Subjects 2 to \<12 years of age will be permitted to enroll in this study only after a Pfizer sponsored pharmacokinetic study confirms the proposed dosage corresponding to this age group is appropriate. * Patients with confirmed Candida infection of the blood, body tissues, or the esophagus. * Patient's doctor feels voriconazole is an appropriate choice of therapy.
Exclusion criteria
* A known allergy to voriconazole or to azole to antifungal drugs. * Females who are pregnant, lactating (breast feeding) or planning a pregnancy during the course of the study, or who are of childbearing potential and not using highly effective method of birth control. * A patient who is receiving treatment with a drug know to interfere with the heart's electrical system (QTc prolongation). * A patient who is receiving treatment with a drug that is not permitted to be used with voriconazole. * For primary therapy: a patient who has received more than 48 hours of antifungal therapy for the current episode of Candida infection. * A patient with significant underlying liver disease at the time of enrollment in the study. * A patient with significant renal disease (CrCl \< 50 ml/min) at the time of enrollment in the study. * A patient with a high likelihood of death within 72 hours of study enrollment due to factors unrelated to Candida infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events - Overall Summary | Baseline up to 1 month follow-up | Percentage of participants with adverse events (AEs), serious adverse events (SAEs), severe AEs, who discontinued due to AEs, or who had dose redued or temporarily discontinued due to AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Global Response of Success at End of Treatment (EOT) | EOT (from 7 to 42 days of treatment) | Global response was determined programmatically based on investigator assessment of clinical and microbiological response. Global response of success was defined as clinical cure or improvement AND microbiological eradication or presumed eradication. Exact 95 percent (%) confidence interval for binomial proportions using Clopper-Pearson method. |
| All-Cause Mortality - Number of Participant Deaths | Day 28 and 1 Month Follow-up | — |
| Time to Death | Baseline up to 1 month follow-up | — |
Countries
China, Czechia, Hong Kong, Hungary, Mexico, Philippines, Poland, Slovakia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Voriconazole: 2 to <12 Years Participants aged 2 to \<12 years (and young adolescents aged 12 to 14 years weighing \<50 kg) with ICC received a loading dose of voriconazole 9 mg/kg), IV, q12h for the first 24 hours, followed by maintenance dosing of voriconazole 8 mg/kg, IV, q12h for a minimum of 5 days of IV therapy. Participants with EC received voriconazole 4 mg/kg, IV, q12h for a minimum of 5 days of IV therapy. In both ICC and EC, once signs and symptoms of Candida infection had resolved and the participant was clinically stable, participants were switched to PO therapy and received voriconazole 9 mg/kg, PO, q12h (maximum dose of 350 mg). Voriconazole was administered for at least 7 days (participants with EC) or 14 days (participants with ICC) after last positive blood culture up to a maximum of 42 days of treatment. | 14 |
| Voriconazole: 12 to <18 Years Participants aged 12 to \<18 years (excluding those aged 12-14 years weighing \<50 kg) with ICC received a loading dose of voriconazole 6 mg/kg, IV, q12h for the first 24 hours, followed by maintenance dosing of voriconazole 4 mg/kg, IV, q12h for a minimum of 7 days of IV therapy. Participants with EC received voriconazole 3 mg/kg, IV, q12h for a minimum of 5 days of IV therapy. In both ICC and EC, once signs and symptoms of Candida infection had resolved and the participant was clinically stable, participants were switched to PO therapy and received voriconazole 200 mg, PO, q12h. Voriconazole was administered for at least 7 days (participants with EC) or 14 days (participants with ICC) after last positive blood culture up to a maximum of 42 days of treatment. | 8 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 1 | 0 |
Baseline characteristics
| Characteristic | Voriconazole: 2 to <12 Years | Voriconazole: 12 to <18 Years | Total |
|---|---|---|---|
| Age, Continuous | 6.8 years STANDARD_DEVIATION 2.9 | 14.4 years STANDARD_DEVIATION 1.7 | 9.5 years STANDARD_DEVIATION 4.5 |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 14 | 6 / 8 |
| serious Total, serious adverse events | 2 / 14 | 1 / 8 |
Outcome results
Primary
Percentage of Participants With Adverse Events - Overall Summary
Percentage of participants with adverse events (AEs), serious adverse events (SAEs), severe AEs, who discontinued due to AEs, or who had dose redued or temporarily discontinued due to AEs.
Time frame: Baseline up to 1 month follow-up
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Voriconazole: 2 to <12 Years | Percentage of Participants With Adverse Events - Overall Summary | With SAEs | 14.3 percentage of participants |
| Voriconazole: 2 to <12 Years | Percentage of Participants With Adverse Events - Overall Summary | Discontinued due to AEs | 14.3 percentage of participants |
| Voriconazole: 2 to <12 Years | Percentage of Participants With Adverse Events - Overall Summary | With severe AEs | 28.6 percentage of participants |
| Voriconazole: 2 to <12 Years | Percentage of Participants With Adverse Events - Overall Summary | Dose reduced/temporary discontinuation due to AE | 21.4 percentage of participants |
| Voriconazole: 2 to <12 Years | Percentage of Participants With Adverse Events - Overall Summary | With AEs | 92.9 percentage of participants |
| Voriconazole: 12 to <18 Years | Percentage of Participants With Adverse Events - Overall Summary | Dose reduced/temporary discontinuation due to AE | 0 percentage of participants |
| Voriconazole: 12 to <18 Years | Percentage of Participants With Adverse Events - Overall Summary | With AEs | 75.0 percentage of participants |
| Voriconazole: 12 to <18 Years | Percentage of Participants With Adverse Events - Overall Summary | With SAEs | 12.5 percentage of participants |
| Voriconazole: 12 to <18 Years | Percentage of Participants With Adverse Events - Overall Summary | With severe AEs | 37.5 percentage of participants |
| Voriconazole: 12 to <18 Years | Percentage of Participants With Adverse Events - Overall Summary | Discontinued due to AEs | 25.0 percentage of participants |
Secondary
All-Cause Mortality - Number of Participant Deaths
Time frame: Day 28 and 1 Month Follow-up
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Voriconazole: 2 to <12 Years | All-Cause Mortality - Number of Participant Deaths | Day 28 | 0 participants |
| Voriconazole: 2 to <12 Years | All-Cause Mortality - Number of Participant Deaths | 1 Month Follow-up | 0 participants |
| Voriconazole: 12 to <18 Years | All-Cause Mortality - Number of Participant Deaths | Day 28 | 0 participants |
| Voriconazole: 12 to <18 Years | All-Cause Mortality - Number of Participant Deaths | 1 Month Follow-up | 0 participants |
Secondary
Percentage of Participants With a Global Response of Success at End of Treatment (EOT)
Global response was determined programmatically based on investigator assessment of clinical and microbiological response. Global response of success was defined as clinical cure or improvement AND microbiological eradication or presumed eradication. Exact 95 percent (%) confidence interval for binomial proportions using Clopper-Pearson method.
Time frame: EOT (from 7 to 42 days of treatment)
Population: Modified Intent-to-Treat (MITT) Population: all participants who received at least 1 dose of study medication and who have confirmed ICC, EC or participants with EC who do not have confirmation of EC by esophagoscopy, but who had at least confirmation of oropharyngeal candidiasis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Voriconazole: 2 to <12 Years | Percentage of Participants With a Global Response of Success at End of Treatment (EOT) | 88.9 percentage of participants |
| Voriconazole: 12 to <18 Years | Percentage of Participants With a Global Response of Success at End of Treatment (EOT) | 62.5 percentage of participants |
Secondary
Time to Death
Time frame: Baseline up to 1 month follow-up
Population: No participants died within the safety reporting period, therefore time to death was not applicable.