E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neonates with suspected or culture-proven candidiasis |
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E.1.1.1 | Medical condition in easily understood language |
Neonates with suspected or culture-proven candidiasis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
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 evaluate the pharmacokinetics of fluconazole and micafungin both administered after randomization in neonates with suspected or culture-proven Candidiasis in order to validate their optimal dosage.
To compare the time to reach the target drug exposure area under the concentration-time curve from 0 to 24 h (AUC0–24) for candidiasis by the two randomly administered drugs. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the tolerability of fluconazole and micafungin in neonates with suspected or culture-proven Candidiasis
To describe short-term safety
To describe short term outcome of treated episodes
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Neonates and infants between 24 up to 42 weeks gestational age and with post-natal age of 48 hours of life up to day of life (DOL) 120 at the time of culture acquisition.
2. Requiring antifungal therapy according to medical decision by the attending physician for microbiologically documented and clinically suspected candida infection independently from the availability of any positive culture for Candida spp.
3. Written informed consent from the parents or the legally authorized representative must be obtained prior to entry.
4. Infant must have sufficient venous access to permit administration of study medication and monitoring of safety variables. |
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E.4 | Principal exclusion criteria |
1. Infant exposed to fluconazole or micafungin prophylaxis prior to inclusion
2. Infant who has received more than 48hours of systemic antifungal therapy (any product) prior to the first dose of study drug for treatment of the current Candida infection
3. Infant with a concomitant medical condition, whose participation, in the opinion of the investigator and / or medical advisor, may create an unacceptable additional risk
4. Infant previously enrolled in this study
5. Infant who is co-infected with a non-Candida fungal organism
6. Neonates with isolated candiduria
7. Infant with any history of a hypersensitivity or severe vasomotor reaction to any echinocandin or fluconazole product
8. Infant with pre-existing hepatic or renal disease
9. Infants with baseline Candida spp. Isolate resistant to fluconazole or micafungin according to EUCAST/CLSI clinical breakpoints (see section 5.2.2 for interpretative MIC criteria) or with an isolate for which treatment with an alternative antifungal agent is indicated, i.e. there is insufficient evidence that the species in question is a good target for therapy with either fluconazole or micafungin. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PK/PD integration of pharmacokinetics and pharmacodynamics |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time to reach the AUC breakpoint ant the ratio of AUC/MIC90s in the two treated groups |
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E.5.2 | Secondary end point(s) |
Definition of efficacy evaluation criteria (primary and secondary) measurement techniques |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The procedures or evaluations will be performed on the days of PK study
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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 | No |
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 | Yes |
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) | No |
E.7.1.1 | First administration to humans | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 45 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial days | 45 |