In a randomized, double-blind study, patients with a proven diagnosis of invasive candidiasis received daily doses of caspofungin acetate for injection (50 mg/day following a 70 mg loading dose on Day 1) or amphotericin B deoxycholate (0.6 to 0.7 mg/kg/day for non-neutropenic patients and 0.7 to 1 mg/kg/day for neutropenic patients). Patients were stratified by both neutropenic status and APACHE II score. Patients with Candida endocarditis, meningitis, or osteomyelitis were excluded from this study. 

Patients who met the entry criteria and received one or more doses of intravenous (IV) study therapy were included in the modified intention-to-treat [MITT] analysis of response at the end of intravenous (IV) study therapy. A favorable response at this time point required both symptom/sign resolution/improvement and microbiological clearance of the Candida infection. 

Two hundred thirty-nine patients were enrolled. Patient disposition is shown in Table 10. 

Of the 239 patients enrolled, 224 met the criteria for inclusion in the MITT population (109 treated with caspofungin acetate for injection and 115 treated with amphotericin B). Of these 224 patients, 186 patients had candidemia (92 treated with caspofungin acetate for injection and 94 treated with amphotericin B). The majority of the patients with candidemia were non-neutropenic (87%) and had an APACHE II score less than or equal to 20 (77%) in both arms. Most candidemia infections were caused by C. albicans (39%), followed by C. parapsilosis (20%), C. tropicalis (17%), C. glabrata (8%), and C. krusei (3%). 

At the end of intravenous (IV) study therapy, caspofungin acetate for injection was comparable to amphotericin B in the treatment of candidemia in the MITT population. For the other efficacy time points (Day 10 of intravenous (IV) study therapy, end of all antifungal therapy, 2-week post-therapy follow-up, and 6- to 8-week post-therapy follow-up), caspofungin acetate for injection was as effective as amphotericin B. 

Outcome, relapse and mortality data are shown in Table 11. 

Overall, across all sites of infection included in the study, the efficacy of caspofungin acetate for injection was comparable to that of amphotericin B for the primary endpoint. 

In this study, the efficacy data for caspofungin acetate for injection in neutropenic patients with candidemia were limited. In a separate compassionate use study, 4 patients with hepatosplenic candidiasis received prolonged therapy with caspofungin acetate for injection following other long-term antifungal therapy; three of these patients had a favorable response. 

In a second randomized, double-blind study, 197 patients with proven invasive candidiasis received caspofungin acetate for injection 50 mg/day (following a 70 mg loading dose on Day 1) or caspofungin acetate for injection 150 mg/day. The diagnostic criteria, evaluation time points, and efficacy endpoints were similar to those employed in the prior study. Patients with Candida endocarditis, meningitis, or osteomyelitis were excluded. 

Although this study was designed to compare the safety of the two doses, it was not large enough to detect differences in rare or unexpected adverse events [see Adverse Reactions (6.1)]. The efficacy of caspofungin acetate for injection at the 150 mg daily dose was not significantly better than the efficacy of the 50 mg daily dose of caspofungin acetate for injection. The efficacy of doses higher than 50 mg daily in the other adult patients for whom caspofungin acetate for injection is indicated has not been evaluated.