Arasertaconazole Nitrate Pessaries - Dose Finding Study for the Vulvovaginal Candidiasis (VVC) Treatment

• Sponsor: Ferrer Internacional S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01144286
• Collaborator: (none)
• Enrollment: 229
• Location: 1
• Arms: 4
• Duration (Months): 9
• Patients Per Site Per Month: 25.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Vulvovaginal Candidiasis	Drug: arasertaconazole nitrate; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 229 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Multi-center, Randomized, Placebo-controlled, Parallel-group, Double-blinded Study to Compare the Therapeutic Efficacy, Safety, and Tolerability of 3 Single Vaginal Doses of Arasertaconazole Nitrate Pessaries in the Treatment of VVC
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo placebo pessary, single dose	Drug: arasertaconazole nitrate; Arasertaconazole nitrate pessary, placebo pessary
Experimental: Arasertaconazole nitrate 150 mg Arasertaconazole nitrate 150 mg pessary, single dose	Drug: arasertaconazole nitrate; Arasertaconazole nitrate pessary, placebo pessary; Drug: placebo; placebo, single dose
Experimental: arasertaconazole nitrate 300 mg Arasertaconazole nitrate 300 mg pessary, single dose	Drug: arasertaconazole nitrate; Arasertaconazole nitrate pessary, placebo pessary; Drug: placebo; placebo, single dose
Experimental: arasertaconazole 600 mg Arasertaconazole nitrate 600 mg pessary, single dose	Drug: arasertaconazole nitrate; Arasertaconazole nitrate pessary, placebo pessary; Drug: placebo; placebo, single dose

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Dose-response of Clinical and Mycological (Global)Therapeutic Response [Day 8 ± 2 days]

   Global therapeutic response at day 8± 2 days. Safety and tolerability.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ferrer Internacional S.A.	Barcelona		Spain	08028

Sponsors and Collaborators

• Ferrer Internacional S.A.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ferrer Internacional S.A.
• ClinicalTrials.gov Identifier: NCT01144286
• Other Study ID Numbers: P-090756-01; 2009-016655-21
• First Posted: Jun 15, 2010
• Last Update Posted: Oct 9, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Ferrer Internacional S.A.: VVC; candidiasis; vaginal candidiasis
• Additional relevant MeSH terms: Candidiasis; Candidiasis, Vulvovaginal

Study Results

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 Detail	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.

Arm/Group Title	Placebo	Arasertaconazole Nitrate 150 mg	Arasertaconazole Nitrate 300 mg	Arasertaconazole 600 mg
Arm/Group Description	placebo pessary, single dose	Arasertaconazole nitrate 150 mg pessary, single dose	Arasertaconazole nitrate 300 mg pessary, single dose	Arasertaconazole nitrate 600 mg pessary, single dose
Period Title: Overall Study
STARTED	57	58	58	56
COMPLETED	57	58	58	56
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Arasertaconazole Nitrate 150 mg	Arasertaconazole Nitrate 300 mg	Arasertaconazole 600 mg	Total
Arm/Group Description	placebo pessary, single dose	Arasertaconazole nitrate 150 mg pessary, single dose	Arasertaconazole nitrate 300 mg pessary, single dose	Arasertaconazole nitrate 600 mg pessary, single dose	Total of all reporting groups
Overall Participants	57	58	58	56	229
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	57 100%	58 100%	58 100%	56 100%	229 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.1 (7.74)	32.8 (8.47)	29.7 (7.58)	31.8 (8.53)	31.1 (8.13)
Sex: Female, Male (Count of Participants)
Female	57 100%	58 100%	58 100%	56 100%	229 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Europe	57 100%	58 100%	58 100%	56 100%	229 100%

Outcome Measures

1. Primary Outcome

Title	Dose-response of Clinical and Mycological (Global) Therapeutic Response
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Arasertaconazole Nitrate 150 mg	Arasertaconazole Nitrate 300 mg	Arasertaconazole 600 mg
Arm/Group Description	placebo pessary, single dose	Arasertaconazole nitrate 150 mg pessary, single dose	Arasertaconazole nitrate 300 mg pessary, single dose	Arasertaconazole nitrate 600 mg pessary, single dose
Measure Participants	57	58	58	56
Number (95% Confidence Interval) [percentage of patients cured]	31.7	48.7	47.6	53.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Arasertaconazole Nitrate 150 mg, Arasertaconazole Nitrate 300 mg, Arasertaconazole 600 mg
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0630
	Comments	Significance level was set to α of 0.05 if the primary endpoint was significant, hierarchical testing was to be performed on the primary endpoint (each active dose X placebo). No other adjustment was made for testing multiple secondary outcomes.
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	response rate (%)
	Estimated Value	80
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Dose-response of Clinical and Mycological (Global)Therapeutic Response
Description	Global therapeutic response at day 8± 2 days. Safety and tolerability.
Time Frame	Day 8 ± 2 days

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	Arasertaconazole Nitrate 150 mg	Arasertaconazole Nitrate 300 mg	Arasertaconazole 600 mg
Arm/Group Description	placebo pessary, single dose	Arasertaconazole nitrate 150 mg pessary, single dose	Arasertaconazole nitrate 300 mg pessary, single dose	Arasertaconazole nitrate 600 mg pessary, single dose
Measure Participants	57	58	58	56
Number (95% Confidence Interval) [percentage of cured participants]	15.6 27.4%	34.2 59%	46.3 79.8%	61.0 108.9%

Adverse Events

Time Frame	Study Initiation Date: 15 June 2010 Study Completion Date: 15 November 2010
Arm/Group Title	Placebo		Arasertaconazole Nitrate 150 mg		Arasertaconazole Nitrate 300 mg		Arasertaconazole 600 mg
Arm/Group Description	placebo pessary, single dose		Arasertaconazole nitrate 150 mg pessary, single dose		Arasertaconazole nitrate 300 mg pessary, single dose		Arasertaconazole nitrate 600 mg pessary, single dose
All Cause Mortality
	Placebo		Arasertaconazole Nitrate 150 mg		Arasertaconazole Nitrate 300 mg		Arasertaconazole 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Arasertaconazole Nitrate 150 mg		Arasertaconazole Nitrate 300 mg		Arasertaconazole 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/58 (0%)		0/58 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Arasertaconazole Nitrate 150 mg		Arasertaconazole Nitrate 300 mg		Arasertaconazole 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/57 (10.5%)		9/58 (15.5%)		13/58 (22.4%)		13/56 (23.2%)
Cardiac disorders
arrhythmia	0/57 (0%)	0	0/58 (0%)	0	1/58 (1.7%)	3	0/56 (0%)	0
Ear and labyrinth disorders
vertigo	0/57 (0%)	0	0/58 (0%)	0	1/58 (1.7%)	1	0/56 (0%)	0
Gastrointestinal disorders
abdominal distension	0/57 (0%)	0	1/58 (1.7%)	1	0/58 (0%)	0	0/56 (0%)	0
nausea	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	1
General disorders
bloody discharge	0/57 (0%)	0	0/58 (0%)	0	1/58 (1.7%)	1	0/56 (0%)	0
Infections and infestations
tonsilitis	1/57 (1.8%)	1	0/58 (0%)	0	0/58 (0%)	0	0/56 (0%)	0
Chamydial infection	1/57 (1.8%)	1	0/58 (0%)	0	0/58 (0%)	0	0/56 (0%)	0
vaginal infection	0/57 (0%)	0	1/58 (1.7%)	1	0/58 (0%)	0	0/56 (0%)	0
nasopharyngitis	0/57 (0%)	0	1/58 (1.7%)	1	0/58 (0%)	0	0/56 (0%)	0
respiratory tract infection	0/57 (0%)	0	1/58 (1.7%)	1	0/58 (0%)	0	0/56 (0%)	0
rhinitis	0/57 (0%)	0	1/58 (1.7%)	1	0/58 (0%)	0	0/56 (0%)	0
influenza	0/57 (0%)	0	0/58 (0%)	0	2/58 (3.4%)	2	0/56 (0%)	0
vaginitis bacterial	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	1
Injury, poisoning and procedural complications
heat stroke	1/57 (1.8%)	1	0/58 (0%)	0	0/58 (0%)	0	0/56 (0%)	0
Investigations
electrocardiogram TWave decreased	0/57 (0%)	0	0/58 (0%)	0	1/58 (1.7%)	1	0/56 (0%)	0
blood bilirrubin increased	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	1
Musculoskeletal and connective tissue disorders
pain in extremity	0/57 (0%)	0	1/58 (1.7%)	1	1/58 (1.7%)	1	0/56 (0%)	0
Nervous system disorders
headache	1/57 (1.8%)	1	2/58 (3.4%)	2	3/58 (5.2%)	3	2/56 (3.6%)	2
migraine	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	1
Pregnancy, puerperium and perinatal conditions
pregnancy	0/57 (0%)	0	0/58 (0%)	0	1/58 (1.7%)	1	1/56 (1.8%)	1
Renal and urinary disorders
urinary incontinence	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	1
Reproductive system and breast disorders
vulvovaginal burning sensation	1/57 (1.8%)	1	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	1
vulvovaginal discomfort	0/57 (0%)	0	0/58 (0%)	0	1/58 (1.7%)	1	0/56 (0%)	0
dyspareunia	0/57 (0%)	0	0/58 (0%)	0	1/58 (1.7%)	1	0/56 (0%)	0
pelvic pain	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	1
uterine haemorrhage	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	2
Respiratory, thoracic and mediastinal disorders
oropharyngeal pain	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	1
rhinitis allergic	0/57 (0%)	0	0/58 (0%)	0	0/58 (0%)	0	1/56 (1.8%)	1
Skin and subcutaneous tissue disorders
pruritus	1/57 (1.8%)	1	1/58 (1.7%)	1	0/58 (0%)	0	0/56 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review publications and/or presentations (results communications) prior to public release and communications regarding trial results for a period that is 60 days from the time submitted to the sponsor for review. The sponsor may require changes to the publication and /or presentation regarding its content or the time of release.