The Study Of Fluconazole For Vulvovaginal Candidiasis

• ClinicalTrials.gov Identifier: NCT01806623
• Recruitment Status: Completed
• First Posted: March 7, 2013
• Results First Posted: December 3, 2014
• Last Update Posted: July 19, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Vulvovaginal Candidiasis
• Intervention: Drug: Fluconazole
• Enrollment: 157

Participant Flow

Recruitment Details
Pre-assignment Details

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
Reason Not Completed
Withdrawal by Subject	1
Adverse Event	1
Did not meet the inclusion criteria	56

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 Number of Baseline Participants		157
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	157 participants
		31.8 (8.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	157 participants
	Female	157 100.0%
	Male	0 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
Overall Number of Participants Analyzed	102
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Day 7 (n=95)	33.7; (24.2 to 44.3)
Day 14 (n=100)	54.2; (43.7 to 64.4)
Day 28 (n=102)	74.7; (65.0 to 82.9)

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
Overall Number of Participants Analyzed	102
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Day 7 (n=99)	34.8; (25.1 to 45.4)
Day 14 (n=101)	57.3; (46.8 to 67.3)
Day 28 (n=102)	81.6; (72.5 to 88.7)

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
Overall Number of Participants Analyzed	102
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Day 7 (n=99)	100.0; (96.1 to 100.0)
Day 14 (n=101)	99.0; (94.3 to 100.0)
Day 28 (n=102)	95.9; (89.9 to 98.9)

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
Overall Number of Participants Analyzed	102
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Day 7 (n=95)	95.7; (89.5 to 98.8)
Day 14 (n=100)	89.8; (82.0 to 95.0)
Day 28 (n=102)	85.9; (77.4 to 92.0)

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
Overall Number of Participants Analyzed	102
Mean (Full Range); Unit of Measure: score on s scale
Day 1 (before dosing, n=102)	11.0; (4 to 19)
Day 3 (n=98)	4.5; (0 to 12)
Day 7 (n=93)	1.8; (0 to 10)
Day 14 (n=98)	0.8; (0 to 7)
Day 28 (n=99)	0.4; (0 to 9)

6. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Description	[Not Specified]
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
Overall Number of Participants Analyzed	157
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg/mL
	3.71; (24%)

7. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax)
Description	[Not Specified]
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
Overall Number of Participants Analyzed	157
Median (Full Range); Unit of Measure: hours
	1.9; (1.8 to 70.3)

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
Overall Number of Participants Analyzed	149
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg*h/mL
	156.1; (22%)

9. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) for Vaginal Fluid Fluconazole Concentration Adjusted by Sample Weight
Description	[Not Specified]
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
Overall Number of Participants Analyzed	157
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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	[Not Specified]
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
Overall Number of Participants Analyzed	157
Median (Full Range); Unit of Measure: hours
	20.5; (1.8 to 116.6)

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
Overall Number of Participants Analyzed	144
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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	[Not Specified]
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
Overall Number of Participants Analyzed	157
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: 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	[Not Specified]
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
Overall Number of Participants Analyzed	157
Median (Full Range); Unit of Measure: hrs
	20.5; (1.8 to 116.6)

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
Overall Number of Participants Analyzed	142
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg*h/mL
	85.3; (48%)

Adverse Events

Time Frame	[Not Specified]
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 (%)
Total	--/--
Serious Adverse Events
	Fluconazole
	Affected / at Risk (%)
Total	0/157 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Fluconazole
	Affected / at Risk (%)
Total	37/157 (23.57%)
Cardiac disorders
Palpitations † 1	1/157 (0.64%)
Gastrointestinal disorders
Abdominal distension † 1	1/157 (0.64%)
Abdominal pain upper † 1	1/157 (0.64%)
Diarrhoea † 1	3/157 (1.91%)
Nausea † 1	3/157 (1.91%)
General disorders
Pyrexia † 1	2/157 (1.27%)
Infections and infestations
Bronchitis † 1	2/157 (1.27%)
Bronchopneumonia † 1	1/157 (0.64%)
Chlamydial infection † 1	1/157 (0.64%)
Cystitis † 1	4/157 (2.55%)
Folliculitis † 1	1/157 (0.64%)
Gastroenteritis † 1	1/157 (0.64%)
Genital herpes † 1	4/157 (2.55%)
Nasopharyngitis † 1	8/157 (5.10%)
Pharyngitis streptococcal † 1	1/157 (0.64%)
Upper respiratory tract infection † 1	1/157 (0.64%)
Vulvovaginitis trichomonal † 1	1/157 (0.64%)
Injury, poisoning and procedural complications
Burns first degree † 1	1/157 (0.64%)
Excoriation † 1	1/157 (0.64%)
Investigations
Blood creatine phosphokinase increased † 1	1/157 (0.64%)
Hepatic enzyme increased † 1	1/157 (0.64%)
Reproductive system and breast disorders
Genital haemorrhage † 1	3/157 (1.91%)
Skin and subcutaneous tissue disorders
Dermatitis contact † 1	1/157 (0.64%)
Eczema † 1	4/157 (2.55%)
Urticaria † 1	1/157 (0.64%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 16.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mikamo H, Matsumizu M, Nakazuru Y, Okayama A, Nagashima M. Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan. J Infect Chemother. 2015 Jul;21(7):520-6. doi: 10.1016/j.jiac.2015.03.011. Epub 2015 Mar 30.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01806623
• Other Study ID Numbers: A0561023
• First Submitted: January 28, 2013
• First Posted: March 7, 2013
• Results First Submitted: August 14, 2014
• Results First Posted: December 3, 2014
• Last Update Posted: July 19, 2021