The Study Of Fluconazole For Vulvovaginal Candidiasis

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01806623
Collaborator
(none)
157
10
1
8.6
15.7
1.8

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

Study Type:
Interventional
Actual Enrollment :
157 participants
Allocation:
N/A
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter Open-label Non-comparative Study Of Fluconazole For The Treatment Of Vulvovaginal Candidiasis.
Actual Study Start Date :
Mar 5, 2013
Actual Primary Completion Date :
Nov 22, 2013
Actual Study Completion Date :
Nov 22, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Fluconazole

Drug: Fluconazole
Single oral dose of 150mg Fluconazole

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. Maximum Observed Plasma Concentration (Cmax) [Before dosing and 2, 24, 48 and 168 hours after dosing]

  6. Time to Reach Maximum Observed Plasma Concentration (Tmax) [Before dosing and 2, 24, 48 and 168 hours after dosing]

  7. 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)

  8. Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight [Before dosing and 2, 24, 48 and 168 hours after dosing]

  9. 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]

  10. 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

  11. 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]

  12. 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]

  13. 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

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
Female
Accepts 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.

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.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01806623
Other Study ID Numbers:
  • A0561023
First Posted:
Mar 7, 2013
Last Update Posted:
Jul 19, 2021
Last Verified:
Jul 1, 2021
Additional relevant MeSH terms:

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

1. Primary Outcome
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%
2. Secondary Outcome
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%
3. Secondary Outcome
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%
4. Secondary Outcome
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%
5. Secondary Outcome
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
6. Secondary Outcome
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)
7. Secondary Outcome
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
8. Secondary Outcome
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)
9. Secondary Outcome
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)
10. Secondary Outcome
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
11. Secondary Outcome
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)
12. Secondary Outcome
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)
13. Secondary Outcome
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
14. Secondary Outcome
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

[Not Specified]

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
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01806623
Other Study ID Numbers:
  • A0561023
First Posted:
Mar 7, 2013
Last Update Posted:
Jul 19, 2021
Last Verified:
Jul 1, 2021