Vulvovaginal Candidiasis
Conditions
Brief summary
As for the indication of vulvovaginal candidiasis, a single oral administration of fluconazole 150 mg has been approved and is recommended by guidelines overseas. However in Japan oral therapy with antifungal triazole such as Fluconazole has not been approved, and topical therapies such as vaginal tablets, pessary and cream are used clinically. The purpose of this trial is to confirm the efficacy and safety of single oral administration of fluconazole 150 mg for the treatment of vulvovaginal candidiasis in Japanese patients.
Interventions
DRUGFluconazole
Single oral dose of 150mg Fluconazole
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with clinical symptoms and signs of vulvovaginal candidiasis. * Patients tested positive for Candida by fungal culture. * Patients who can agree not to have intercourse up to 28 days after dosing.
Exclusion criteria
* Patients with a history of hypersensitivity to fluconazole. * Patients with severe renal dysfunction. * Patients with liver disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Therapeutic Outcome: Response Rate | Day 7, Day 14 and Day 28 | Therapeutic outcome was determined by combination of clinical efficacy and mycological efficacy for each participant as Effective, Ineffective or Indeterminate. The therapeutic outcome was considered as Effective when the clinical efficacy was Cure and the mycological efficacy was Eradication. Primary evaluation of therapeutic outcome was on Day 28. Response rate was calculated based on the following formula, the number of participants assessed as effective over total participants excluding ones assessed as indeterminate multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Efficacy: Cure and Improvement Rate | Day 7, Day 14 and Day 28 | Scores of severity in signs and symptoms on each observation dates are compared with those before the treatment and the clinical efficacy is determined as Cure (the clinical symptom disappeared), Improvement (the clinical symptom was improved), Failure (the criteria for Cure and Improvement were not met, or other systemic antifungal drugs or local antifungal drugs were administered for the treatment of the disease to be examined) or Indeterminate (efficacy for each item was not determined for the reasons including failure to conduct the test, or other systemic antifungal agents or local antifungal drugs were administered for the treatment of infections other than the disease to be examined). Cure and improvement rate was calculated based on the following formula, the number of participants assessed as Cure or Improvement over total participants excluding ones assessed as Indeterminate multiplied by 100. |
| Mycological Efficacy: Eradication Rate | Day 7, Day 14 and Day 28 | Determined based on the results of culture of Candida as Eradication, Persistent or Indeterminate. Eradication rate was calculated based on the following formula, the number of participants assessed as Eradication over total participants excluding ones assessed as Indeterminate multiplied by 100. |
| Total Scores for Clinical Symptoms | Day 1 (before dosing), Day 3, Day 7, Day 14 and Day 28 | Sum of severity scores in vulvovaginal itching, vulvovaginal burning sensation, excoriation of vulva, vaginal discharge, vulva oedema, redness of vulva, vaginal redness, property of vaginal content. Higher scores show greater severity. Total Scores for Clinical Symptoms Severity range from 0 (best possible outcome) to 24 (worst possible outcome). |
| Maximum Observed Plasma Concentration (Cmax) | Before dosing and 2, 24, 48 and 168 hours after dosing | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Before dosing and 2, 24, 48 and 168 hours after dosing | — |
| Area Under the Plasma Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Before dosing and 2, 24, 48 and 168 hours after dosing | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Clinical Efficacy: Cure Rate | Day 7, Day 14 and Day 28 | Scores of severity in signs and symptoms at each observation dates were compared with those before the treatment and the clinical efficacy was determined as Cure (the clinical symptom disappeared), Improvement (the clinical symptom was improved: the total score of clinical symptom was reduced relative to the total score before the treatment), Failure (the criteria for Cure and Improvement were not met, or other systemic antifungal drugs or local antifungal drugs were administered for the treatment of the disease to be examined) or Indeterminate (efficacy for each item was not determined for the reasons including failure to conduct the test, or other systemic antifungal agents or local antifungal drugs were administered for the treatment of infections other than the disease to be examined). Cure rate was calculated based on the following formula, the number of participants assessed as Cure over total participants excluding ones assessed as Indeterminate multiplied by 100. |
| Time to Reach Maximum Observed Concentration (Tmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight | Before dosing and 2, 24, 48 and 168 hours after dosing | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight | Before dosing and 2, 24, 48 and 168 hours after dosing | Area under the concentration time-curve from zero to the last measured concentration (AUClast) for Vaginal Fluid Fluconazole Concentration adjusted by Sample Weight |
| Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid | Before dosing and 2, 24, 48 and 168 hours after dosing | — |
| Time to Reach Maximum Observed Concentration (Tmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid | Before dosing and 2, 24, 48 and 168 hours after dosing | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid | Before dosing and 2, 24, 48 and 168 hours after dosing | Area under the concentration time-curve from zero to the last measured concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid |
| Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight | Before dosing and 2, 24, 48 and 168 hours after dosing | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluconazole Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment | 157 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Did not meet the inclusion criteria | 56 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Fluconazole |
|---|---|
| Age, Continuous | 31.8 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 157 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 37 / 157 |
| serious Total, serious adverse events | 0 / 157 |
Outcome results
Primary
Therapeutic Outcome: Response Rate
Therapeutic outcome was determined by combination of clinical efficacy and mycological efficacy for each participant as Effective, Ineffective or Indeterminate. The therapeutic outcome was considered as Effective when the clinical efficacy was Cure and the mycological efficacy was Eradication. Primary evaluation of therapeutic outcome was on Day 28. Response rate was calculated based on the following formula, the number of participants assessed as effective over total participants excluding ones assessed as indeterminate multiplied by 100.
Time frame: Day 7, Day 14 and Day 28
Population: The modified-Intent to Treat (m-ITT) included participants with vulvovaginal candidiasis who received the investigational products, who tested positive for Candida in the vulva and/or vagina at Day 1 (before dosing), and whose clinical efficacy was evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluconazole | Therapeutic Outcome: Response Rate | Day 7 (n=95) | 33.7 percentage of participants |
| Fluconazole | Therapeutic Outcome: Response Rate | Day 14 (n=100) | 54.2 percentage of participants |
| Fluconazole | Therapeutic Outcome: Response Rate | Day 28 (n=102) | 74.7 percentage of participants |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid
Area under the concentration time-curve from zero to the last measured concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid
Time frame: Before dosing and 2, 24, 48 and 168 hours after dosing
Population: The vaginal discharge parameter analysis set was defined as those participants who were included in the vaginal discharge concentration analysis set and for whom at least one set of vaginal discharge parameters was calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fluconazole | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid | 85.3 mcg*h/mL | Geometric Coefficient of Variation 48 |
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight
Area under the concentration time-curve from zero to the last measured concentration (AUClast) for Vaginal Fluid Fluconazole Concentration adjusted by Sample Weight
Time frame: Before dosing and 2, 24, 48 and 168 hours after dosing
Population: The vaginal discharge parameter analysis set was defined as those participants who were included in the vaginal discharge concentration analysis set and for whom at least one set of vaginal discharge parameters was calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fluconazole | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight | 79.5 mcg*h/g | Geometric Coefficient of Variation 43 |
Secondary
Area Under the Plasma Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: Before dosing and 2, 24, 48 and 168 hours after dosing
Population: The plasma parameter analysis set was defined as those participants who were included in the plasma concentration analysis set and for whom at least one set of plasma concentration parameters was calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fluconazole | Area Under the Plasma Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 156.1 mcg*h/mL | Geometric Coefficient of Variation 22 |
Secondary
Clinical Efficacy: Cure and Improvement Rate
Scores of severity in signs and symptoms on each observation dates are compared with those before the treatment and the clinical efficacy is determined as Cure (the clinical symptom disappeared), Improvement (the clinical symptom was improved), Failure (the criteria for Cure and Improvement were not met, or other systemic antifungal drugs or local antifungal drugs were administered for the treatment of the disease to be examined) or Indeterminate (efficacy for each item was not determined for the reasons including failure to conduct the test, or other systemic antifungal agents or local antifungal drugs were administered for the treatment of infections other than the disease to be examined). Cure and improvement rate was calculated based on the following formula, the number of participants assessed as Cure or Improvement over total participants excluding ones assessed as Indeterminate multiplied by 100.
Time frame: Day 7, Day 14 and Day 28
Population: The modified-Intent to Treat (m-ITT) included participants with vulvovaginal candidiasis who received the investigational products, who tested positive for Candida in the vulva and/or vagina at Day 1 (before dosing), and whose clinical efficacy was evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluconazole | Clinical Efficacy: Cure and Improvement Rate | Day 7 (n=99) | 100.0 percentage of participants |
| Fluconazole | Clinical Efficacy: Cure and Improvement Rate | Day 14 (n=101) | 99.0 percentage of participants |
| Fluconazole | Clinical Efficacy: Cure and Improvement Rate | Day 28 (n=102) | 95.9 percentage of participants |
Secondary
Clinical Efficacy: Cure Rate
Scores of severity in signs and symptoms at each observation dates were compared with those before the treatment and the clinical efficacy was determined as Cure (the clinical symptom disappeared), Improvement (the clinical symptom was improved: the total score of clinical symptom was reduced relative to the total score before the treatment), Failure (the criteria for Cure and Improvement were not met, or other systemic antifungal drugs or local antifungal drugs were administered for the treatment of the disease to be examined) or Indeterminate (efficacy for each item was not determined for the reasons including failure to conduct the test, or other systemic antifungal agents or local antifungal drugs were administered for the treatment of infections other than the disease to be examined). Cure rate was calculated based on the following formula, the number of participants assessed as Cure over total participants excluding ones assessed as Indeterminate multiplied by 100.
Time frame: Day 7, Day 14 and Day 28
Population: The modified-Intent to Treat (m-ITT) included participants with vulvovaginal candidiasis who received the investigational products, who tested positive for Candida in the vulva and/or vagina at Day 1 (before dosing), and whose clinical efficacy was evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluconazole | Clinical Efficacy: Cure Rate | Day 7 (n=99) | 34.8 percentage of participants |
| Fluconazole | Clinical Efficacy: Cure Rate | Day 14 (n=101) | 57.3 percentage of participants |
| Fluconazole | Clinical Efficacy: Cure Rate | Day 28 (n=102) | 81.6 percentage of participants |
Secondary
Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid
Time frame: Before dosing and 2, 24, 48 and 168 hours after dosing
Population: The vaginal discharge parameter analysis set was defined as those participants who were included in the vaginal discharge concentration analysis set and for whom at least one set of vaginal discharge parameters was calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fluconazole | Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid | 1.53 mcg/mL | Geometric Coefficient of Variation 59 |
Secondary
Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight
Time frame: Before dosing and 2, 24, 48 and 168 hours after dosing
Population: The vaginal discharge parameter analysis set was defined as those participants who were included in the vaginal discharge concentration analysis set and for whom at least one set of vaginal discharge parameters was calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fluconazole | Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight | 1.33 mcg/g | Geometric Coefficient of Variation 49 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Before dosing and 2, 24, 48 and 168 hours after dosing
Population: The plasma parameter analysis set was defined as those participants who were included in the plasma concentration analysis set and for whom at least one set of plasma concentration parameters was calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Fluconazole | Maximum Observed Plasma Concentration (Cmax) | 3.71 mcg/mL | Geometric Coefficient of Variation 24 |
Secondary
Mycological Efficacy: Eradication Rate
Determined based on the results of culture of Candida as Eradication, Persistent or Indeterminate. Eradication rate was calculated based on the following formula, the number of participants assessed as Eradication over total participants excluding ones assessed as Indeterminate multiplied by 100.
Time frame: Day 7, Day 14 and Day 28
Population: The modified-Intent to Treat (m-ITT) included participants with vulvovaginal candidiasis who received the investigational products, who tested positive for Candida in the vulva and/or vagina at Day 1 (before dosing), and whose clinical efficacy was evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluconazole | Mycological Efficacy: Eradication Rate | Day 14 (n=100) | 89.8 percentage of participants |
| Fluconazole | Mycological Efficacy: Eradication Rate | Day 28 (n=102) | 85.9 percentage of participants |
| Fluconazole | Mycological Efficacy: Eradication Rate | Day 7 (n=95) | 95.7 percentage of participants |
Secondary
Time to Reach Maximum Observed Concentration (Tmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid
Time frame: Before dosing and 2, 24, 48 and 168 hours after dosing
Population: The vaginal discharge parameter analysis set was defined as those participants who were included in the vaginal discharge concentration analysis set and for whom at least one set of vaginal discharge parameters was calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluconazole | Time to Reach Maximum Observed Concentration (Tmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid | 20.5 hrs |
Secondary
Time to Reach Maximum Observed Concentration (Tmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight
Time frame: Before dosing and 2, 24, 48 and 168 hours after dosing
Population: The vaginal discharge parameter analysis set was defined as those participants who were included in the vaginal discharge concentration analysis set and for whom at least one set of vaginal discharge parameters was calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluconazole | Time to Reach Maximum Observed Concentration (Tmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight | 20.5 hours |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Before dosing and 2, 24, 48 and 168 hours after dosing
Population: The plasma parameter analysis set was defined as those participants who were included in the plasma concentration analysis set and for whom at least one set of plasma concentration parameters was calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fluconazole | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 1.9 hours |
Secondary
Total Scores for Clinical Symptoms
Sum of severity scores in vulvovaginal itching, vulvovaginal burning sensation, excoriation of vulva, vaginal discharge, vulva oedema, redness of vulva, vaginal redness, property of vaginal content. Higher scores show greater severity. Total Scores for Clinical Symptoms Severity range from 0 (best possible outcome) to 24 (worst possible outcome).
Time frame: Day 1 (before dosing), Day 3, Day 7, Day 14 and Day 28
Population: The modified-Intent to Treat (m-ITT) included participants with vulvovaginal candidiasis who received the investigational products, who tested positive for Candida in the vulva and/or vagina at Day 1 (before dosing), and whose clinical efficacy was evaluated.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Fluconazole | Total Scores for Clinical Symptoms | Day 1 (before dosing, n=102) | 11.0 score on s scale |
| Fluconazole | Total Scores for Clinical Symptoms | Day 3 (n=98) | 4.5 score on s scale |
| Fluconazole | Total Scores for Clinical Symptoms | Day 7 (n=93) | 1.8 score on s scale |
| Fluconazole | Total Scores for Clinical Symptoms | Day 14 (n=98) | 0.8 score on s scale |
| Fluconazole | Total Scores for Clinical Symptoms | Day 28 (n=99) | 0.4 score on s scale |