MGCD290 and Fluconazole Versus Fluconazole Alone for the Treatment of Moderate to Severe Vulvovaginal Candidiasis

A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Fluconazole Versus Fluconazole And MGCD290 for the Treatment of Moderate to Severe Vulvovaginal Candidiasis

The primary objective of the study is to evaluate the rate of therapeutic cure of the combination treatment of MGCD290 and fluconazole as compared to that of fluconazole alone at Test of Cure Visit for patients with moderate to severe vulvovaginal candidiasis.

Study Overview

• Status: Completed
• Conditions: Vulvovaginal Candidiasis
• Intervention / Treatment: Drug: MGCD290

Detailed Description

MGCD290 is a novel antifungal agent targeting the Hos2 enzyme in fungi. MGCD290 was shown to potentiate and broaden the spectrum of activity of azole antifungal agents in vitro, especially fluconazole. MGCD290 taken together with fluconazole was observed to be safe in healthy volunteer studies. The current study is evaluating both the efficacy and safety of the combination treatment in subjects with moderate to severe vulvovaginal candidiasis.

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • San Diego, California, United States, 92123
      • Women's Health Care Research Corp.
  • Florida
    • Lake Worth, Florida, United States, 33461
      • Altus Research
    • North Miami, Florida, United States, 33161
      • Healthcare Clinical Data, Inc.
  • Georgia
    • Augusta, Georgia, United States, 30912-3500
      • Georgia Health Sciences University
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Clinical Trials Management
    • Metairie, Louisiana, United States, 70006
      • Clinical Trials Management, LLC
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89123
      • Clinical Research of Nevada
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Lyndhurst Clinical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Lyndhurst Clinical Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University College of Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Womens Hospital of UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
  • Texas
    • Irving, Texas, United States, 75061
      • Brownstone Clinical Trials
  • Utah
    • Sandy, Utah, United States, 84070
      • Physician's Research Options
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Tidewater Physicians for Women
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Vulvovaginal candidiasis infection is diagnosed, the symptoms evaluated using a numerical rating system based on severity (absent=0; mild=1; moderate=2; severe=3) with a minimum VVC Composite Signs/Symptoms score of 7.
• Subject with normal vaginal pH (≤4.5) upon evaluation.
• Subject completes the informed consent process.
• Subject agrees to take study medication when scheduled. Subject has no difficulty swallowing the medication.
• Subject complies with all clinical trial instructions. Commits to all follow-up visits.
• Subject is free of any disease or physical condition which might impair the evaluation of safety and/or vulvovaginal candidiasis.
• Subject of childbearing potential has a negative urine pregnancy test at screening.
• Subject of childbearing potential agrees to use an effective, non-prohibited form of birth control for the duration of clinical trial or until onset of menses following the administration of study medication, whichever is longer. She must be on a stable regimen of oral contraceptives, contraceptive implant or depot injection, contraceptive patch, IUD, condom and spermicidal agent, diaphragm and spermicidal agent, or sexual abstinence for at least the past 60 days.
• Subject agrees to abstain from sexual intercourse from the time of randomization through the first seven days immediately following treatment.
• Direct microscopic examination with KOH must be positive at screening showing yeast forms (hyphae/pseudohyphae) or budding yeasts.
• Aged 18 and over, post-menarcheal, and not surgically or naturally post-menopausal.

Exclusion Criteria:

• Sensitivity to ingredients in the study medications.
• Subject currently participates in, or has within 30 days prior to this clinical trial participated in, an investigational clinical trial.
• Subject experienced 4 or more episodes of VVC in the past 12 months.
• Subjects with other causes of vulvovaginitis.
• Subjects with active HPV infection.
• Subjects with other urogenital infections that would potentially alter their response to disease.
• Subjects with confirmed Neisseria gonorrhea or Chlamydia trachomatis.
• Subjects with abnormal PAP test results except for ASC-US with confirmed absence of High-Risk HPV infection.
• Subjects who will be under treatment or have surgery during the study period for cervical intraepithelial neoplasia or cervical carcinoma.
• Subjects with a planned major surgery during the time of the study.
• Pregnant or nursing subjects.
• Subjects menstruating at enrollment.
• History of hypersensitivity to azoles.
• Evidence/history of ventricular dysfunction such as congestive heart failure, unstable coronary artery disease, significant cardiac arrhythmias or proarrhythmic conditions associated with prolongation of QT interval.
• History of clinically significant ECG abnormalities, including QTc prolongation.
• Current treatment with: erythromycin, astemizole, pimozide, quinidine, and cisapride)
• History of cancer or currently being treated for a cancer.
• Subject is immunocompromised or has chronic mucocutaneous candidiasis.
• Use of systemic immunosuppressants such as cyclosporine, TNF inhibitors and tacrolimus.
• History of liver toxicity with other drugs.
• History of hepatic or renal impairment.
• Subjects with diabetes mellitus with poor glycemic control (HgbA1C >7%).
• Subjects with any other concurrent significant uncontrolled illness.
• Use of oral antifungals within 14 days immediately prior to enrollment.
• Use of systemic corticosteroids within 30 days immediately prior to enrollment (inhaled corticosteroids are permitted).
• Use of any topical vaginal products within 1 week prior to enrollment.
• Subject is a substance abuser such that the abuse may result in lack of study compliance.
• Vaginal pessaries and rings used for contraception or hormone replacement therapy.
• Subject used an antibiotic within 24 hours immediately prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MGCD290 and Fluconazole; Oral Administration of MGCD290 and Fluconazole	Drug: MGCD290; 1 Oral Dose Administration
No Intervention: Fluconazole; This is an Active Comparator: Oral Administration of Fluconazole with Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Therapeutic Cure Rate	28 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Mycological Cure Rate	Day 14 and Day 28
Clinical Cure Rate	Day 14 and Day 28
Therapeutic Cure Rate	Day 14
Recurrence Rate	Day 28
Time to Resolution of Symptoms	First 14 days post-dose
Improvement in Symptoms	Day 14

Collaborators and Investigators

• Sponsor: MethylGene Inc.
• Investigators: Study Director: Gregory Reid, MSc, MBA, MethylGene Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: December 20, 2011
• First Submitted That Met QC Criteria: December 21, 2011
• First Posted (Estimate): December 22, 2011

Study Record Updates

• Last Update Posted (Estimate): April 4, 2013
• Last Update Submitted That Met QC Criteria: April 2, 2013
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Double-Blind; Moderate to Severe; Phase II; Placebo-Controlled; Acute; Vulvovaginal Candidiasis; Treatment of Moderate to Severe Vulvovaginal Candidiasis
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Vaginal Diseases; Vulvar Diseases; Vaginitis; Vulvitis; Vulvovaginitis; Candidiasis; Candidiasis, Vulvovaginal
• Other Study ID Numbers: 290-005