E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Fungal Infection |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of disease caused by Candida albicans |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042941 |
E.1.2 | Term | Systemic fungal infection NOS |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the pharmacokinetics of voriconazole following multiple dosing with intravenous voriconazole in children aged 2 to less than (<)12 years.
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and toleration of multiple dose administration of voriconazole in children requiring treatment for the prevention of systemic fungal infection; and to evaluate the plasma concentrations of the major metabolite of voriconazole (N-oxide) in these subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Children (both male and female) aged from 2 to <12 years who required treatment for the prevention of systemic fungal infection.
2. Children who were expected to develop neutropenia lasting for more than 10 days following chemotherapy for one of the following conditions:
a. leukaemia
b. lymphoma
c. aplastic anaemia
d. as the preparative regimen for bone marrow transplantation
3. Subjects who were anticipated to live for more than three months.
4. Females of childbearing potential must have had a negative pregnancy test at entry. |
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E.4 | Principal exclusion criteria |
1. Subjects who were receiving and could not discontinue the following drugs at least 24 hours prior to study start:
Terfenadine and cisapride (due to the possibility of QTc prolongation with these drugs)
Omeprazole (an inhibitor of CYP2C19) which is known to increase plasma voriconazole levels.
Subjects who had received the following drugs within 14 days prior to study entry:
Rifampicin, rifabutin, carbamazepine, phenytoin, nevirapine and barbiturates as these are inducers of hepatic enzymes and may result in undetectable levels of voriconazole.
2. Subjects who had received astemizole within the previous 60 days.
3. Subjects with any clinically significant abnormality following review of screening laboratory data other than that associated with their underlying disease. Aspartate transaminase (AST) and alanine transaminase (ALT) had to be <5 * upper limit of normal.
4. Subjects who were taking or were likely to receive any investigational drug except: those used for the treatment of child’s cancer, antiretroviral agents and drugs used for treatment of any acquired immune deficiency syndrome (AIDS) defining opportunistic infections, all of which were allowed.
5. Subjects with a history of hypersensitivity to or severe intolerance of azole antifungal agents.
6. Subjects who had already been entered into this protocol once.
7. Subjects with moderate and severe renal impairment (
i.e. calculated creatinine clearance <30 millilitre per minute (ml/min). If creatinine clearance was reduced to <30 ml/min at any time during the study, the subject had to be discontinued from the study. Creatinine clearance was calculated using the equation
Creatinine Clearance (ml/min) = 0.55*height (cm)/serum creatinine (mg/dL)
8. Subjects with a medical history or current evidence of cardiac arrhythmia.
9 Any other condition which, in the opinion of the investigator, would make the subject unsuitable for enrollment.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Plasma Concentration of Voriconazole on Day 4.
2. Plasma Concentration of Voriconazole on Day 8. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Pre-dose and end of infusion on Day 4.
2. Pre-dose and end of infusion on Day 8. |
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E.5.2 | Secondary end point(s) |
1. Number of Subjects with Treatment Emergent Adverse Event and Serious Adverse Event.
2. Plasma Concentration of Voriconazole (N-oxide) on Day 4 and Day 8. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to Day 21.
2. Pre-dose and end of infusion on Day 4 and Day 8. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 26 |