Recurrent Vulvovaginal Candidiasis
Conditions
Brief summary
Recurrent vulvovaginal candidiasis (RVVC), also known as recurrent yeast infections, is defined as at least 3 episodes of acute vulvovaginal candidiasis (VVC) in the past 12 months. Several properties of oteseconazole (VT-1161) suggest it might be a safer and more effective treatment of RVVC than other oral antifungal medications. This study will evaluate the effectiveness and safety of oteseconazole (VT-1161) for the treatment of acute VVC episodes in patients with RVVC and consists of 2 parts. The first part of the study is a 2-week induction phase for the treatment of the patient's current VVC episode when the patient will take either fluconazole or oteseconazole (VT-1161) according to a random assignment. The second part consists of an 11-week maintenance phase, when the patient will take either oteseconazole (VT-1161) or a placebo according to the random assignment from the first part of the study, and then a 37-week follow-up period.
Interventions
600mg administered on Day 1 and 450mg administered on Day 2, followed by 150mg administered once weekly for 11 weeks staring on Day 14.
DRUGFluconazole 150mg capsule
150mg administered every 72 hours in 3 sequential doses starting on Day 1.
DRUGPlacebo
Administered once weekly starting on Day 14.
Sponsors
Mycovia Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 3 or more episodes of acute VVC in the past 12 months * Positive KOH test * Total vulvovaginal signs and symptoms score of ≥3 at screening visit * Total vulvovaginal signs and symptoms score of \<3 at Day 14 * Must be able to swallow pills
Exclusion criteria
* Presence or a history of another vaginal or vulvar condition(s) * Evidence of major organ system disease * History of cervical cancer * Poorly controlled diabetes mellitus * Pregnant * Recent use of topical or systemic antifungal or antibacterial drugs * Recent use of immunosuppressive or systemic corticosteroid therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population | 48 Weeks | The primary efficacy outcome measure was the percentage of subjects with 1 or more culture-verified acute VVC episodes during the maintenance phase (post-randomization through Week 48) in the intent-to-treat population, which includes subjects who failed to clear their initial acute VVC episode during the induction phase. An acute VVC episode during the maintenance phase (considered a recurrent episode) was defined as a positive fungal culture for Candida species and a clinical signs and symptoms score of ≥3. To calculate the signs and symptoms score, each vulvovaginal sign (erythema, edema, excoriation) and symptom (itching, burning, irritation) was scored using the following scale, with a higher score indicating a worse outcome. 0 = none (complete absence of any sign or symptom), 1 = mild (slight), 2 = moderate (definitely present), 3 = severe (marked, intense) |
Countries
United States
Participant flow
Recruitment details
After providing consent, 251 subjects were screened and, of those, a total of 219 subjects were randomly assigned to the oteseconazole or fluconazole/placebo group for a 2-week induction phase. During the induction phase, subjects received either oteseconazole or fluconazole. Subjects whose presenting acute VVC episode resolved during the induction phase (a total of 185 subjects) entered a 48-week maintenance phase comprised of an 11-week treatment period and a 37-week follow-up period.
Pre-assignment details
Of the 251 subjects screened, 32 did not meet eligibility requirements and were not enrolled (i.e., not assigned to a treatment arm for the 2-week induction phase).
Participants by arm
| Arm | Count |
|---|---|
| Oteseconazole (VT-1161) 600mg on Day 1 and 450mg on Day 2, followed by 150mg once weekly for 11 weeks starting on Day 14. | 147 |
| Fluconazole / Placebo 150mg fluconazole every 72 hours in 3 sequential doses starting on Day 1, followed by placebo once weekly for 11 weeks starting on Day 14. | 72 |
| Total | 219 |
Baseline characteristics
| Characteristic | Oteseconazole (VT-1161) | Total | Fluconazole / Placebo |
|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 10.7 | 35 years STANDARD_DEVIATION 11 | 36 years STANDARD_DEVIATION 11.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 74 Participants | 27 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 9 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 88 Participants | 130 Participants | 42 Participants |
| Region of Enrollment United States | 147 participants | 219 participants | 72 participants |
| Sex: Female, Male Female | 147 Participants | 219 Participants | 72 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 146 | 1 / 123 | 0 / 72 | 0 / 62 |
| other Total, other adverse events | 8 / 146 | 35 / 123 | 8 / 72 | 21 / 62 |
| serious Total, serious adverse events | 0 / 146 | 3 / 123 | 0 / 72 | 1 / 62 |
Outcome results
Primary
Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population
The primary efficacy outcome measure was the percentage of subjects with 1 or more culture-verified acute VVC episodes during the maintenance phase (post-randomization through Week 48) in the intent-to-treat population, which includes subjects who failed to clear their initial acute VVC episode during the induction phase. An acute VVC episode during the maintenance phase (considered a recurrent episode) was defined as a positive fungal culture for Candida species and a clinical signs and symptoms score of ≥3. To calculate the signs and symptoms score, each vulvovaginal sign (erythema, edema, excoriation) and symptom (itching, burning, irritation) was scored using the following scale, with a higher score indicating a worse outcome. 0 = none (complete absence of any sign or symptom), 1 = mild (slight), 2 = moderate (definitely present), 3 = severe (marked, intense)
Time frame: 48 Weeks
Population: Analysis was performed on the ITT population which includes subjects who failed to clear their initial acute VVC episode during the induction phase. The ITT population was defined as all randomized subjects. Missing values were imputed with multiple imputation using the following auxiliary information: treatment, baseline body mass index, baseline age, ethnicity, and visit. The 'percentage of participants' measure represents an average of 10 individual tests using multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oteseconazole (VT-1161) | Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population | 5.1 percentage of participants |
| Fluconazole / Placebo | Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population | 42.2 percentage of participants |