Safety Results from a Phase 3, Randomized, Double-Blind, Double- Dummy Study of Anidulafungin (ANID) vs. Fluconazole (FLU) in Patients (Pts) with Esophageal Candidiasis (EC)

DAVID KRAUSE, MD, WILLIAM BIRMINGHAM,JENNIFER SCHRANZ, MD,

Author address: 

Vicuron Pharmaceuticals, King of Prussia, PA

Abstract: 

Background: Systemic therapy is recommended for EC, but the antifungal armamentarium is limited. ANID is a novel antifungal agent of the echinocandin class. ANID has potent activity against medically significant fungi, including Candida and Aspergillus spp. We conducted a large, multinational Phase 3 trial of ANID in pts with EC. Methods: Patients (pts) received IV ANID (100 mg loading dose, then 50 mg/day) plus oral placebo or oral FLU (200 mg loading dose, then 100 mg/day) plus IV vehicle control for 21 days. Vital signs were taken throughout the treatment period and physical examinations were performed periodically. Adverse events (AEs) were collected daily. Potentially clinically significant (PCS) lab abnormalities and categorical shifts from baseline were prospectively defined, and electrocardiograms were performed at baseline and at peak plasma drug concentrations. Results: 601 pts in 4 countries were randomized. Most pts had AIDS. Demographics in the 2 groups were similar, mean age was 37y. Most pts in both groups received therapy for 13-15 days. The majority of AEs were attributable to underlying medical conditions (AIDS and malnutrition). The most commonly reported AEs in both groups were pyrexia, headache, diarrhea, vomiting, and nausea. 43 deaths occurred during the study (23 ANID, 20 FLU). Treatment-related (per blinded investigator attribution) AEs (TRAEs) occurred in 9.6% of ANID pts and 12.9% of FLU pts. No TRAE occurred in 2.0% of ANID pts; 2.3% FLU pts had increased AST. Six (6) pts were unblinded at the investigator’s request during the study due to a serious AE (SAE), 3 in each group. TRSAEs were infrequent, 2 occurred in each group. The % of pts with PCS lab abnormalities and categorical shifts was similar between groups at baseline and throughout the study. No treatment-related effect on QT interval occurred. In both groups, there was no discernable pattern of toxicity. Conclusion: In pts with EC, ANID 50 mg/day was well tolerated, and as safe as FLU 100 mg/day.
2003

abstract No: 

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Full conference title: 

41st Annual Meeting Infectious Diseases Society of America
    • Infectious Diseases Society of America 41st