Vulvovaginal Candidiasis
Conditions
Keywords
VVC, candidiasis, vaginal candidiasis
Brief summary
In order to find an optimal dose of arasertaconazole nitrate in the treatment of vulvovaginal candidiasis, a multicenter, randomized, double-blind, parallel, placebo-controlled study will be conducted to compare the therapeutic efficacy, safety and tolerability of three different doses of arasertaconazole nitrate (150 mg, 300 mg or 600 mg, pessaries).
Interventions
DRUGarasertaconazole nitrate
Arasertaconazole nitrate pessary, placebo pessary
DRUGplacebo
placebo, single dose
Sponsors
Ferrer Internacional S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Women aged between 18 to 65 years of age who have signed the informed consent. * Not pregnant, not nursing. * No indication of other vulvovaginitis or genital infections * Positive 10% potassium hydroxide (KOH) preparation for budding yeast and/or pseudohyphae. * Negative wet mount results for T. vaginalis and clue cells. *
Exclusion criteria
* Subjects with another vaginal or vulvar condition that would confound the interpretation of clinical response. * Hypersensitivity to imidazole products administered topically. * Any other medical condition which in the opinion of the investigator could interfere with study conduct.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-response of Clinical and Mycological (Global) Therapeutic Response | day 26 ± 4 days | Global therapeutic response at day 26± 4 days (TOC- Test-of-Cure visit).Global therapeutic response is a composite endpoint using the clinical (signs and symptoms) and the mycological cures (microbiological culture), according to FDA guideline Vulvovaginal Candidiasis -Developing Antimicrobial Drugs for Treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose-response of Clinical and Mycological (Global)Therapeutic Response | Day 8 ± 2 days | Global therapeutic response at day 8± 2 days. Safety and tolerability. |
Countries
Spain
Participant flow
Recruitment details
The subjects were randomized to a treatment arm using an interactive web response system (IWRS). Placebo and study drug pessaries were dispensed as a kit, and all subjects were instructed in proper self-administration of the pessaries (at bedtime while lying down). Study initiation date was 15June2010 and completed on 15 Nov 2010.
Pre-assignment details
After signed informed consent, VVC clinical signs and symptoms were assessed,(KOH) wet mounts and samples for mycological culture obtained.Baseline safety assessments, including pregnancy were performed. If all inclusion criteria and none of the exclusion criteria were met, the subject was randomized in the same day to one of the treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo pessary, single dose | 57 |
| Arasertaconazole Nitrate 150 mg Arasertaconazole nitrate 150 mg pessary, single dose | 58 |
| Arasertaconazole Nitrate 300 mg Arasertaconazole nitrate 300 mg pessary, single dose | 58 |
| Arasertaconazole 600 mg Arasertaconazole nitrate 600 mg pessary, single dose | 56 |
| Total | 229 |
Baseline characteristics
| Characteristic | Arasertaconazole Nitrate 150 mg | Arasertaconazole Nitrate 300 mg | Placebo | Arasertaconazole 600 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants | 58 Participants | 57 Participants | 56 Participants | 229 Participants |
| Age Continuous | 32.8 years STANDARD_DEVIATION 8.47 | 29.7 years STANDARD_DEVIATION 7.58 | 30.1 years STANDARD_DEVIATION 7.74 | 31.8 years STANDARD_DEVIATION 8.53 | 31.1 years STANDARD_DEVIATION 8.13 |
| Region of Enrollment Europe | 58 participants | 58 participants | 57 participants | 56 participants | 229 participants |
| Sex: Female, Male Female | 58 Participants | 58 Participants | 57 Participants | 56 Participants | 229 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 57 | 9 / 58 | 13 / 58 | 13 / 56 |
| serious Total, serious adverse events | 0 / 57 | 0 / 58 | 0 / 58 | 0 / 56 |
Outcome results
Primary
Dose-response of Clinical and Mycological (Global) Therapeutic Response
Global therapeutic response at day 26± 4 days (TOC- Test-of-Cure visit).Global therapeutic response is a composite endpoint using the clinical (signs and symptoms) and the mycological cures (microbiological culture), according to FDA guideline Vulvovaginal Candidiasis -Developing Antimicrobial Drugs for Treatment.
Time frame: day 26 ± 4 days
Population: The full analysis set (FAS) was the primary population for the analysis of all efficacy endpoints. The FAS was defined as all randomized subjects who received at least 1 dose of a study drug.Subjects in the FAS were analyzed according to randomized treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Dose-response of Clinical and Mycological (Global) Therapeutic Response | 31.7 percentage of patients cured |
| Arasertaconazole Nitrate 150 mg | Dose-response of Clinical and Mycological (Global) Therapeutic Response | 48.7 percentage of patients cured |
| Arasertaconazole Nitrate 300 mg | Dose-response of Clinical and Mycological (Global) Therapeutic Response | 47.6 percentage of patients cured |
| Arasertaconazole 600 mg | Dose-response of Clinical and Mycological (Global) Therapeutic Response | 53.8 percentage of patients cured |
Comparison: Primary analysis is the dose response at TOC based on the global therapeutic cure. Dose response will be tested using a logistic regression using linear coefficient for the treatment effect(Wald chi-square).~Assuming that the response rate is 80% for 600 mg, 75% for the 300 mg, 65% for 150 mg and 50% for the placebo group, a sample size of 45 subjects in each group will have 90% power to detect a linear dose response using a 0.05 two-sided test of trend based on the logistic model.p-value: 0.063Regression, Logistic
Secondary
Dose-response of Clinical and Mycological (Global)Therapeutic Response
Global therapeutic response at day 8± 2 days. Safety and tolerability.
Time frame: Day 8 ± 2 days
Population: Dose response tested using logistic regression-linear coefficient for treatment effect.Assuming response rate 80% for 600 mg, 75% for 300 mg, 65% for 150 mg and 50% for the placebo group, sample size of 45 subjects in each group have 90% power to detect linear dose response with 0.05 two-sided test of trend based on the logistic model.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Dose-response of Clinical and Mycological (Global)Therapeutic Response | 15.6 percentage of cured participants |
| Arasertaconazole Nitrate 150 mg | Dose-response of Clinical and Mycological (Global)Therapeutic Response | 34.2 percentage of cured participants |
| Arasertaconazole Nitrate 300 mg | Dose-response of Clinical and Mycological (Global)Therapeutic Response | 46.3 percentage of cured participants |
| Arasertaconazole 600 mg | Dose-response of Clinical and Mycological (Global)Therapeutic Response | 61.0 percentage of cured participants |