1330. Fluconazole and MGCD290 in vulvo vaginal candidiasis (VVC):  Results from a randomized phase II study
Session: Poster Abstract Session: Clinical Trials
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background:

VVC is most commonly caused by Candida albicans, although non-albicans species and azole-resistant strains are becoming more prevalent. MGCD290 is a first in class, orally available, small molecule inhibitor of the fungal enzyme Hos2. In vitro, MGCD290 in combination with fluconazole reverses fluconazole resistance.  In murine models of systemic candidiasis, the combination of fluconazole and MGCD290 significantly improved survival compared to either component alone in both azole cross-resistant and azole-sensitive models. 

Methods:

All randomized patients had moderate or severe VVC, as defined by the protocol: mean symptom score was 9.9 in the experimental and 9.4 in the control arms. 220 subjects were randomized in a 1:1 ratio to 1 dose each of: 150mg fluconazole + 540mg MGCD290, or 150mg fluconazole + placebo. Subjects were dosed on Day 1, and followed for 28 days. The primary endpoint was therapeutic cure at 28 days. To achieve therapeutic cure, a patient must have achieved both clinical cure (resolution of all baseline signs and symptoms of VVC) and mycologic cure. Secondary endpoints included therapeutic cure at day 14, and mycologic and clinical cures at day 14 and day 28.

Results:

There was no statistically significant difference between the rate of therapeutic cure at 28 days of subjects treated with MGCD290 plus fluconazole (n=86) compared with the rate of therapeutic cure in the control arm (fluconazole plus placebo, n=85) (p=0.879). There were no statistically significant differences between the control and experimental arms at the secondary endpoints.

There were no serious adverse events and non-serious adverse events were balanced between the experimental and control arms. 

Conclusion:

The addition of MGCD290 at a dose of 540 mg orally x 1 in combination with fluconazole was well tolerated but did not significantly improve the outcome of VVC compared with fluconazole alone in patients with moderate or severe VVC. Local concentrations of MGCD290 in vaginal fluid may have been insufficient and future studies should evaluate higher doses. Based on the observed synergy with azoles in preclinical models and well tolerated safety profile, evaluation in systemic candidiasis and onychomycosis is recommended.

Michael Augenbraun, MD, FACP1, Jeff Livingston, MD2, Robert Parker, MD3, Samuel Lederman, MD4, Steven Chavoustie, MD5, Franklin Morgan, MD6, Gregory Reid, MSc7, Laura Pearce7, Rachel Humphrey, MD8, Jeffrey Besterman, PhD7, Jack Sobel, MD, FIDSA9 and The 290-005 Trial investigators, (1)SUNY Downstate Medical Center, Brooklyn, NY, (2)Brownstone Clinical Trials, LLC, Irving, TX, (3)Lyndhurst Clinical Research, Winston-Salem, NC, (4)Altus Research, Lake Worth, FL, (5)Healthcare Clinical Data, Inc, North Miami, FL, (6)Tidewater Clinical Research, Virginia Beach, VA, (7)MethylGene Inc., Montreal, QC, Canada, (8)MethylGene US Inc., Princeton, NJ, (9)Wayne State University/Detroit Medical Center/Harp, Detroit, MI

Disclosures:

M. Augenbraun, MethylGene Inc.: Investigator, Research support
Beckman Coulter: Investigator, Research grant

J. Livingston, MethylGene Inc.: Investigator, Research support

R. Parker, MethylGene Inc.: Investigator, Research support

S. Lederman, MethylGene Inc.: Investigator, Research support

S. Chavoustie, MethylGene Inc.: Investigator, Research support

F. Morgan, MethylGene Inc.: Investigator, Research support

G. Reid, MethylGene Inc.: Employee, Salary

L. Pearce, MethylGene Inc.: Consultant, Consulting fee

R. Humphrey, MethylGene Inc.: Employee, Salary

J. Besterman, MethylGene Inc.: Employee, Salary

J. Sobel, MethylGene Inc.: Investigator, Research support

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