Micafungin Versus AmBisome in Invasive Candidiasis and Candidemia

• Clinical response (complete, partial, stabilization, progression) during the treatment period and the post-treatment period [ Time Frame: During the 2 to 8 week treatment period and the 12 week post treatment followup period ] [ Designated as safety issue: No ]
• Mycological response (eradication, presumed eradication, persistence) during the treatment period and the post-treatment period [ Time Frame: During the 2 to 8 week treatment period and the 12 week post treatment followup period ] [ Designated as safety issue: No ]
• Overall incidence of emergent and recurrent fungal infections at the End of Study [ Time Frame: End of the 12 week post treatment followup peroid ] [ Designated as safety issue: No ]
• Independent Efficacy Review Committee's assessment of overall treatment success [ Time Frame: Prior to database lock ] [ Designated as safety issue: No ]
• Peak change of estimated glomerular filtration rate during the treatment period compared to Baseline [ Time Frame: During the 2 to 8 week treatment period ] [ Designated as safety issue: No ]
• Incidence of acute infusion related reactions as pre-defined [ Time Frame: During the 2 to 8 week treatment period ] [ Designated as safety issue: No ]
• Patient survival at the End of Therapy and at the End of Study [ Time Frame: End of the 2 to 8 week treatment period and end of the 12 week post treatment followup period ] [ Designated as safety issue: No ]
• Overall incidence of Adverse Events (AE) [ Time Frame: Throughout study and post treatment followup period ] [ Designated as safety issue: No ]

• Clinical response (complete, partial, stabilization, progression) during the treatment period and the post-treatment period
• Mycological response (eradication, presumed eradication, persistence) during the treatment period and the post-treatment period
• Overall incidence of emergent and recurrent fungal infections at the End of Study
• Independent Efficacy Review Committee’s assessment of overall treatment success
• Peak change of estimated glomerular filtration rate during the treatment period compared to Baseline
• Incidence of acute infusion related reactions as pre-defined
• Patient survival at the End of Therapy and at the End of Study
• Overall incidence of Adverse Events (AE)

The purpose of this study is to determine the efficacy and safety of micafungin (FK463) versus liposomal amphotericin B (AmBisome) in treating neutropenic and non-neutropenic patients with confirmed invasive candidiasis or candidemia. Enrollment will include adult and pediatric patients.

A phase III, multicenter, double-blind, comparative, parallel, randomized study. Enrollment will include adult and pediatric patients. The adult population is sized to test for non-inferiority. For the pediatric population, descriptive analyses are planned.

• Drug: Micafungin
  IV
  Other Names:

  • Mycamine
  • FK463
• Drug: Liposomal Amphotericin B
  IV
  Other Name: AmBisome

• Experimental: 1
  Intervention: Drug: Micafungin
• Active Comparator: 2
  Intervention: Drug: Liposomal Amphotericin B

• Shorr AF, Wu C, Kothari S. Outcomes with micafungin in patients with candidaemia or invasive candidiasis due to Candida glabrata and Candida krusei. J Antimicrob Chemother. 2011 Feb;66(2):375-80. Epub 2010 Dec 8.
• Dupont BF, Lortholary O, Ostrosky-Zeichner L, Stucker F, Yeldandi V. Treatment of candidemia and invasive candidiasis in the intensive care unit: post hoc analysis of a randomized, controlled trial comparing micafungin and liposomal amphotericin B. Crit Care. 2009;13(5):R159. Epub 2009 Oct 5.
• Queiroz-Telles F, Berezin E, Leverger G, Freire A, van der Vyver A, Chotpitayasunondh T, Konja J, Diekmann-Berndt H, Koblinger S, Groll AH, Arrieta A; Micafungin Invasive Candidiasis Study Group. Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial. Pediatr Infect Dis J. 2008 Sep;27(9):820-6.
• Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, Sekhon JS, Freire A, Ramasubramanian V, Demeyer I, Nucci M, Leelarasamee A, Jacobs F, Decruyenaere J, Pittet D, Ullmann AJ, Ostrosky-Zeichner L, Lortholary O, Koblinger S, Diekmann-Berndt H, Cornely OA; Micafungin Invasive Candidiasis Working Group. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. 2007 May 5;369(9572):1519-27.

Inclusion Criteria:

Patients either non-neutropenic with absolute neutrophil counts >= 500 cells/mm3 or neutropenic with absolute neutrophil counts < 500 cells/mm3 must have:

• Candidemia or invasive candidiasis,
• Confirmation and typical clinical signs and symptoms by fungal culture and/or histology,
• Positive culture obtained no more than four days prior to the first dose of study medication.

Exclusion Criteria:

• Patient is pregnant or nursing
• Patients with evidence of liver disease as defined by: a) SGOT/AST or SGPT/ALT > 10 times the upper limit of normal (ULN); or b) Total bilirubin > 5 times ULN.
• Patients whose sole diagnosis is oropharyngeal and/or esophageal candidiasis and/or with positive cultures of urine specimens, sputum specimens, bronchoalveolar-lavage specimens or samples from indwelling drains.
• Patients who have received prophylactic/empiric therapy with azoles or conventional amphotericin B for more than three days within one week prior to enrollment. Neutropenic patients, however, may have received prophylactic azoles without time restrictions.