Study to Compare the Efficacy and Safety of Micafungin Versus Conventional Amphotericin B for the Treatment of Neonatal Candidiasis

Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive at one week following the last dose of study drug with a mycological response of eradication and no requirement for alternative systemic antifungal therapy for continued treatment. Eradication was defined as culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 hours apart, or for Candida meningitis and/or candiduria, 1 negative culture.

Time frame: One week after the last dose of study drug (maximum of 49 days)

Population: Full Analysis Set (all randomized infants who were administered any amount of study drug)

Clinical response assessments were based on the following definitions and assessed by the DRP: * Complete Response: Resolution of all attributable signs related to fungal infection, if present at baseline. * Partial Response: Improvement in attributable signs related to the fungal infection, if present at baseline. * Stabilization: Minor improvement or no change in attributable signs related to the fungal infection, if present at baseline, and infant continued on therapy without deterioration. * Progression: Deterioration in attributable signs related to the fungal infection, if present at baseline; or if death occurred presumably related to a fungal infection.

Time frame: Baseline and end of study drug therapy; maximum of 42 days

Population: Full analysis set participants with clinical signs and symptoms related to the fungal Infection at Baseline

Clinical response assessments were based on the following definitions and assessed by the DRP: * Complete Response: Resolution of all attributable signs related to fungal infection, if present at baseline. * Partial Response: Improvement in attributable signs related to the fungal infection, if present at baseline. * Stabilization: Minor improvement or no change in attributable signs related to the fungal infection, if present at baseline, and infant continued on therapy without deterioration. * Progression: Deterioration in attributable signs related to the fungal infection, if present at baseline; or if death occurred presumably related to a fungal infection.

Time frame: Baseline and one week after the last dose of study drug (maximum of 49 days)

Population: Full analysis set participants with clinical signs and symptoms related to the fungal Infection at Baseline

End-organ dissemination was assessed through abdominal ultrasound and/or computed tomography (CT), echocardiogram, head imaging and retinal exam. Each specific finding, documented by 1 of these techniques, was evaluated as follows: * Improvement: Improvement in size, number or density of identified lesions. Complete response was not expected but may have been documented. * Stabilization: Minor improvement or no change in size, number or density of identified lesions. * Worsening: Increase in size or number of identified lesions.

Time frame: Baseline and 30 days after the last dose of study drug (maximum of 72 days)

Population: Full analysis set participants with end-organ assessments

Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive at the end of study drug therapy with a mycological response of eradication based upon the DRP assessment and no requirement for alternative systemic antifungal therapy for continued treatment.

Time frame: The end of study drug therapy; maximum of 42 days

Population: Participants in the full analysis set with end-organ dissemination

Fungal-free survival was assessed by an independent data review panel (DRP). Fungal-free survival is defined as the percentage of participants alive one week after last dose of study drug with a mycological response of eradication based upon the DRP assessment and no requirement for alternative systemic antifungal therapy for continued treatment.

Time frame: One week after the last dose of study drug (maximum of 49 days)

Population: Participants in the full analysis set with end-organ dissemination

Mycological response assessments were based on the following definitions and assessed by the DRP: * Eradication: Culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 h apart; for Candida meningitis and/or candiduria, 1 negative culture. * Persistence: Continued isolation or histological documentation from a normally sterile site.

Time frame: End of study drug therapy; maximum of 42 days

Population: Full analysis set

Mycological response assessments were based on the following definitions and assessed by the DRP: * Eradication: Culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 h apart; for Candida meningitis and/or candiduria, 1 negative culture. * Persistence: Continued isolation or histological documentation from a normally sterile site.

Time frame: One week after the last dose of study drug (maximum of 49 days)

Population: Full analysis set

An emergent fungal infection is defined as * An invasive fungal infection which is detected at any time during the study that is a non-Candida organism, or * An invasive fungal infection which is detected during the treatment or post-treatment period with a Candida species identified other than those detected at Baseline. If this occurred within 96 hours of the first dose of study drug, the infection was considered part of the final diagnosis of enrolling infection and not an emergent infection.

Time frame: Up to 30 days after the last dose of study drug (maximum of 72 days)

Population: Full analysis set

A recurrent infection is defined as a systemic fungal infection in an infant with eradication at the end of study drug therapy, who developed positive blood cultures or a mycologically confirmed deep-seated Candida infection, with the same species as the enrolling infection.

Time frame: Up to 30 days after the last dose of study drug (maximum of 72 days)

Population: Participants in the full analysis set with eradication at the end of study drug therapy.

Time frame: 15 minutes post intravenous infusion (IV), 4-8 hours post IV and 15-24 hours post IV

Population: The pharmacokinetics (PK) analysis set, including those infants who received any amount of study drug, have at least one study drug concentration, and have dosing and blood collection date and time data sufficient for inclusion in a population pharmacokinetic analysis.

Time to mycological clearance of invasive candidiasis is defined as the time from first dose to the day of mycological eradication for baseline invasive candidiasis infection. Eradication was defined as a culture or histologically documented absence of the infecting Candida species from all positive normally sterile sites during therapy, documented by 2 negative samples, drawn at least 24 hours apart, or for for Candida meningitis and/or candiduria, 1 negative culture. Infants without eradication during the treatment period and who survived were censored at one day after the end of treatment. Infants without eradication who died before completing the treatment period or were lost to follow-up during the treatment were censored at their death or last contact day.

Time frame: From first dose up to 30 days after the last dose of study drug (maximum of 72 days)

Population: Full analysis set

Time to a positive clinical response is defined as the time from the first dose to the day during the treatment period that a positive clinical response (defined as a complete response or partial response) is observed for the first time, assessed by the Investigator. Complete Response is defined as the resolution of all attributable signs related to fungal infection, if present at baseline and Partial Response is defined as improvement in attributable signs related to the fungal infection, if present at baseline. Infants without positive responses and who survived were censored at one day post the end of treatment. Infants without positive responses who died before completing the treatment period, or were lost to follow-up during the treatment were censored at their death or last contact day.

Time frame: From first dose up to 30 days after the last dose of study drug (maximum of 72 days)

Population: Full analysis set participants with clinical signs and symptoms related to the fungal Infection at Baseline