A Phase 3 Study of Micafungin Versus Amphotericin B Deoxycholate in Infants With Invasive Candidiasis.

Abstract

BACKGROUND:

Amphotericin B deoxycholate (AmB-D) is standard of care treatment for neonatal invasive candidiasis (IC). Micafungin (MCA) has broad-spectrum fungicidal activity against Candida spp. We compared the efficacy and safety of intravenous MCA with intravenous AmB-D and assessed the pharmacokinetics of MCA in infants >2-120 days of age with proven IC in a phase 3, randomized, double-blind, multicenter, parallel-group, noninferiority study (NCT00815516).

METHODS:

Infants were randomized 2:1 to MCA (10 mg/kg/d) or AmB-D (1 mg/kg/d) for ≥21 days. Primary efficacy endpoint was fungal-free survival (FFS) 1 week after last study drug dose. MCA population pharmacokinetics included simulated area under the curve (AUC) at steady state and maximum plasma concentration after 2-hour infusion. AUC pharmacodynamic target exposure was 170 µg·h/mL.

RESULTS:

Thirty infants received MCA (n = 20) or AmB-D (n = 10). The trial was terminated early because of slow recruitment. FFS was observed in 12 of 20 [60%; 95% confidence interval (CI): 36%-81%] MCA-group infants and in 7 of 10 (70%; 95% CI: 35%-93%) AmB-D-group infants. The most common treatment-emergent adverse events were anemia [MCA: n = 9 (45%); AmB-D: n = 3 (30%)] and thrombocytopenia [n = 2 (10%) and n = 3 (30%), respectively]. Model-derived mean AUC at steady state for MCA was 399.3 ± 163.9 µg·h/mL (95% prediction interval: 190.3-742.3 µg/mL); steady state and maximum plasma concentration after 2-hour infusion was 31.1 ± 10.5 µg/mL (95% prediction interval: 17.0-49.7 µg/mL). MCA exposures were above the AUC pharmacodynamic target exposure.

CONCLUSIONS:

Within the study limitations, infants with IC treated with MCA achieved similar FFS compared with AmB-D. Both agents were safe and well tolerated.

• Authors: Daniel K Benjamin Jr, David A Kaufman, William W Hope, P Brian Smith, Antonio Arrieta, Paolo Manzoni, Laura L Kovanda, Christopher Lademacher, Brigit Isaacson, Deborah Jednachowski, Chunzhang Wu, Atsunori Kaibara, Thomas J Walsh
• Journal: The Pediatric infectious disease journal (Pediatr Infect Dis J) Vol. 37 Issue 10 Pg. 992-998 (10 2018) ISSN: 1532-0987 [Electronic] United States
• PMID: 29596222 (Publication Type: Clinical Trial, Phase III, Equivalence Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Drug Combinations
• Deoxycholic Acid
• Amphotericin B
• amphotericin B, deoxycholate drug combination
• Micafungin

Topics

• Administration, Intravenous
• Amphotericin B (pharmacokinetics, therapeutic use)
• Antifungal Agents (pharmacokinetics, therapeutic use)
• Area Under Curve
• Candida (drug effects)
• Candidiasis, Invasive (blood, drug therapy)
• Deoxycholic Acid (pharmacokinetics, therapeutic use)
• Double-Blind Method
• Drug Combinations
• Female
• Hematologic Tests
• Humans
• Infant
• Infant, Newborn
• Male
• Micafungin (pharmacokinetics, therapeutic use)
• Treatment Outcome