The Study Of Fluconazole For Vulvovaginal Candidiasis
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Fluconazole
|
Drug: Fluconazole
Single oral dose of 150mg Fluconazole
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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)
- Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight [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 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
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Ai WOMEN'S CLINIC | Asahikawa | Hokkaido | Japan | 070-8003 |
2 | Shirokane Ladies' Clinic | Minato-ku | Tokyo | Japan | 108-0071 |
3 | Takane Medical Clinic | Shinagawa-ku | Tokyo | Japan | 140-0013 |
4 | Suzuran Clinic | Suginami-ku | Tokyo | Japan | 167-0051 |
5 | Mori Ladies Clinic | Fukuoka | Japan | 810-0011 | |
6 | IZUMI Ladies' Clinic | Gifu | Japan | 502-0914 | |
7 | Tetsu-Nakamura Obstetrics and Gynecology Department Internal Medicine | Kagoshima | Japan | 892-0845 | |
8 | Women's Clinic Kamimura | Okayama | Japan | 700-0901 | |
9 | Sutou Ladies Clinic | Osaka | Japan | 542-0081 | |
10 | Hayakawa Clinic | Osaka | Japan | 542-0086 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- A0561023
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Period Title: Overall Study | |
STARTED | 157 |
COMPLETED | 99 |
NOT COMPLETED | 58 |
Baseline Characteristics
Arm/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Overall Participants | 157 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
31.8
(8.5)
|
Sex: Female, Male (Count of Participants) | |
Female |
157
100%
|
Male |
0
0%
|
Outcome Measures
Title | Therapeutic Outcome: Response Rate |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 102 |
Day 7 (n=95) |
33.7
21.5%
|
Day 14 (n=100) |
54.2
34.5%
|
Day 28 (n=102) |
74.7
47.6%
|
Title | Clinical Efficacy: Cure Rate |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 102 |
Day 7 (n=99) |
34.8
22.2%
|
Day 14 (n=101) |
57.3
36.5%
|
Day 28 (n=102) |
81.6
52%
|
Title | Clinical Efficacy: Cure and Improvement Rate |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 102 |
Day 7 (n=99) |
100.0
63.7%
|
Day 14 (n=101) |
99.0
63.1%
|
Day 28 (n=102) |
95.9
61.1%
|
Title | Mycological Efficacy: Eradication Rate |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 102 |
Day 7 (n=95) |
95.7
61%
|
Day 14 (n=100) |
89.8
57.2%
|
Day 28 (n=102) |
85.9
54.7%
|
Title | Total Scores for Clinical Symptoms |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 102 |
Day 1 (before dosing, n=102) |
11.0
|
Day 3 (n=98) |
4.5
|
Day 7 (n=93) |
1.8
|
Day 14 (n=98) |
0.8
|
Day 28 (n=99) |
0.4
|
Title | Maximum Observed Plasma Concentration (Cmax) |
---|---|
Description | |
Time Frame | Before dosing and 2, 24, 48 and 168 hours after dosing |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 157 |
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL] |
3.71
(24)
|
Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) |
---|---|
Description | |
Time Frame | Before dosing and 2, 24, 48 and 168 hours after dosing |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 157 |
Median (Full Range) [hours] |
1.9
|
Title | Area Under the Plasma Curve From Time Zero to Last Quantifiable Concentration (AUClast) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 149 |
Geometric Mean (Geometric Coefficient of Variation) [mcg*h/mL] |
156.1
(22)
|
Title | Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight |
---|---|
Description | |
Time Frame | Before dosing and 2, 24, 48 and 168 hours after dosing |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 157 |
Geometric Mean (Geometric Coefficient of Variation) [mcg/g] |
1.33
(49)
|
Title | Time to Reach Maximum Observed Concentration (Tmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight |
---|---|
Description | |
Time Frame | Before dosing and 2, 24, 48 and 168 hours after dosing |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 157 |
Median (Full Range) [hours] |
20.5
|
Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 144 |
Geometric Mean (Geometric Coefficient of Variation) [mcg*h/g] |
79.5
(43)
|
Title | Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid |
---|---|
Description | |
Time Frame | Before dosing and 2, 24, 48 and 168 hours after dosing |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 157 |
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL] |
1.53
(59)
|
Title | Time to Reach Maximum Observed Concentration (Tmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid |
---|---|
Description | |
Time Frame | Before dosing and 2, 24, 48 and 168 hours after dosing |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 157 |
Median (Full Range) [hrs] |
20.5
|
Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Vaginal Fluid Fluconazole Concentration Adjusted by Potassium in Vaginal Fluid |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Fluconazole |
---|---|
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment |
Measure Participants | 142 |
Geometric Mean (Geometric Coefficient of Variation) [mcg*h/mL] |
85.3
(48)
|
Adverse Events
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |
Arm/Group Title | Fluconazole | |
Arm/Group Description | Three fluconazole 50 mg capsules were orally administered once on the first day of the treatment | |
All Cause Mortality |
||
Fluconazole | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Fluconazole | ||
Affected / at Risk (%) | # Events | |
Total | 0/157 (0%) | |
Other (Not Including Serious) Adverse Events |
||
Fluconazole | ||
Affected / at Risk (%) | # Events | |
Total | 37/157 (23.6%) | |
Cardiac disorders | ||
Palpitations | 1/157 (0.6%) | |
Gastrointestinal disorders | ||
Abdominal distension | 1/157 (0.6%) | |
Abdominal pain upper | 1/157 (0.6%) | |
Diarrhoea | 3/157 (1.9%) | |
Nausea | 3/157 (1.9%) | |
General disorders | ||
Pyrexia | 2/157 (1.3%) | |
Infections and infestations | ||
Bronchitis | 2/157 (1.3%) | |
Bronchopneumonia | 1/157 (0.6%) | |
Chlamydial infection | 1/157 (0.6%) | |
Cystitis | 4/157 (2.5%) | |
Folliculitis | 1/157 (0.6%) | |
Gastroenteritis | 1/157 (0.6%) | |
Genital herpes | 4/157 (2.5%) | |
Nasopharyngitis | 8/157 (5.1%) | |
Pharyngitis streptococcal | 1/157 (0.6%) | |
Upper respiratory tract infection | 1/157 (0.6%) | |
Vulvovaginitis trichomonal | 1/157 (0.6%) | |
Injury, poisoning and procedural complications | ||
Burns first degree | 1/157 (0.6%) | |
Excoriation | 1/157 (0.6%) | |
Investigations | ||
Blood creatine phosphokinase increased | 1/157 (0.6%) | |
Hepatic enzyme increased | 1/157 (0.6%) | |
Reproductive system and breast disorders | ||
Genital haemorrhage | 3/157 (1.9%) | |
Skin and subcutaneous tissue disorders | ||
Dermatitis contact | 1/157 (0.6%) | |
Eczema | 4/157 (2.5%) | |
Urticaria | 1/157 (0.6%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title | Pfizer ClinicalTrials.gov Call Center |
---|---|
Organization | Pfizer, Inc. |
Phone | 1-800-718-1021 |
ClinicalTrials.gov_Inquiries@pfizer.com |
- A0561023