Clinical trial NCT01497223: MGCD290 and Fluconazole Versus Fluconazole Alone for the Treatment of Moderate to Severe Vulvovaginal Candidiasis
Official title: A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Fluconazole Versus Fluconazole And MGCD290 for the Treatment of Moderate to Severe Vulvovaginal Candidiasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Vulvovaginal Candidiasis
Keywords: Phase II
Double-Blind
Placebo-Controlled
Vulvovaginal Candidiasis
Moderate to Severe
Acute
Treatment of Moderate to Severe Vulvovaginal Candidiasis
Lead sponsor: MethylGene Inc.
Sponsor class: INDUSTRY
First posted: 2011-12-22
Enrollment: 220
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Therapeutic Cure Rate
timeFrame: 28 Days
Secondary outcomes:
measure: Mycological Cure Rate
timeFrame: Day 14 and Day 28
measure: Clinical Cure Rate
timeFrame: Day 14 and Day 28
measure: Therapeutic Cure Rate
timeFrame: Day 14
measure: Recurrence Rate
timeFrame: Day 28
measure: Time to Resolution of Symptoms
timeFrame: First 14 days post-dose
measure: Improvement in Symptoms
timeFrame: Day 14
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Diego
country: United States
facility: Women's Health Care Research Corp.
state: California
city: Lake Worth
country: United States
facility: Altus Research
state: Florida
city: North Miami
country: United States
facility: Healthcare Clinical Data, Inc.
state: Florida
city: Augusta
country: United States
facility: Georgia Health Sciences University
state: Georgia
city: Covington
country: United States
facility: Clinical Trials Management
state: Louisiana
city: Metairie
country: United States
facility: Clinical Trials Management, LLC
state: Louisiana
city: Detroit
country: United States
facility: Harper University Hospital
state: Michigan
city: Las Vegas
country: United States
facility: Clinical Research of Nevada
state: Nevada
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Raleigh
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Irving
country: United States
facility: Brownstone Clinical Trials
state: Texas
city: Sandy
country: United States
facility: Physician's Research Options
state: Utah
city: Norfolk
country: United States
facility: Tidewater Physicians for Women
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: MethylGene Inc.
name: Gregory Reid, MSc, MBA
role: STUDY_DIRECTOR
References: