Evaluate Long-Term Safety and Efficacy WC3011 (Estradiol Vaginal Cream)

Study Overview
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Brief Summary
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This is an open-label extension study evaluating the long-term safety and efficacy of WC3011 in non-hysterectomized, healthy, postmenopausal women with vulvovaginal atrophy.

Official Title
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A Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of WC3011 (Estradiol Vaginal Cream) in the Treatment of Symptoms of Vulvovaginal Atrophy in Postmenopausal Women

Conditions
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Vulvovaginal Atrophy

Intervention / Treatment
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* Drug: WC3011 Estradiol Vaginal Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed Study PR-04409.3 (NCT01400776) Exclusion Criteria: Developed any of the following during Study-PR04409.3 or has begun taking hormone therapy other than WC3011: Hypersensitivity to estrogen and/or progestin therapy Known or suspected premalignant or malignant disease (except successfully treated skin cancers) Manifestation of or treatment for significant cardiovascular disease, stroke or ischemic attack Insulin-dependent diabetes mellitus Smoking ≥ 15 cigarettes daily Uncontrolled hypertension - systolic blood pressure (BP) ≥ 160 mmHG or diastolic ≥ 95 mmHg

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WC3011 Estradiol Vaginal Cream<br>WC3011 estradiol vaginal cream 3 times a week for up to 40 weeks. | Drug: WC3011 Estradiol Vaginal Cream<br>* WC3011 estradiol vaginal cream, 3 times a week for 40 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Endometrial Biopsy Results at Final Visit | The endometrial biopsy results was categorized as: normal results categorized as atrophic/inactive or proliferative, unsatisfactory with endometrial thickness ≤4 mm and missing biopsy with endometrial thickness ≤4 mm; abnormal results categorized as polyp, hyperplasia, and carcinoma; unknown result categorized as unsatisfactory with endometrial thickness >4 mm, missing biopsy with endometrial thickness >4 mm, unsatisfactory without transvaginal ultrasonography (TVU) result and missing biopsy without TVU result. The duration of estradiol exposure was combination of studies PR-04409.3 and PR-04509. | Final Visit (Day closest to Day 281) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Participants Self-Assessment of the Symptoms of Vulvovaginal Atrophy (VVA) at Each Post-baseline Timepoints | Self-Assessment of the symptoms of VVA was evaluated for vaginal dryness, vaginal Itching, dysuria, and dyspareunia by a questionnaire. Questionnaire consisted of 5 questions scaled from 0 to 3 level of intensity, where 0-none indicated symptom not present; 1-mild indicated symptom is present but may be intermittent; does not interfere with your activities or lifestyle; 2-moderate indicated symptom is present, aware of the symptom but activities and lifestyle are only occasionally affected; 3-severe indicated usually aware and bothered by the symptom and have modified your activities and/or lifestyle due to the symptom. Higher score indicated most bothersome symptoms. A negative change from Baseline indicates improvement. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study. | Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Weeks 4, 8, 16, 24, 32, 40 and Final Visit (Day closest to Day 281) | 
| Change From Baseline in Vaginal Cytology: Percentage of Superficial Vaginal Cells | Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of superficial cells. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study. | Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Week 40 and Final Visit (Day closest to Day 281) | 
| Change From Baseline in Vaginal Cytology: Percentage of Parabasal Vaginal Cells | Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of parabasal cells. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study. | Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Week 40 and Final Visit (Day closest to Day 281) | 
| Change From Baseline in Vaginal pH | Vaginal pH was obtained at final visit of the study. The pH was a numeric value from 0 to 14 expressing the acidity or alkalinity of the vaginal fluids where 7 was neutral, lower values were more acidic (values of 0-6) and higher values more alkaline (values of 8-14). A negative change from Baseline indicates improvement. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study. | Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Week 40 and Final Visit (Day closest to Day 281) | 
| Change From Baseline as Per Investigator's Assessment of Each of the Signs of VVA | Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to the signs of VVA: atrophy, pallor, vaginal dryness, friability, and petechiae scored on a 4-point scale where: 0=none, 1=mild, 2=moderate, or 3= severe. The negative change from Baseline indicates improvement. Participants at Final visit/Visit 7 included those who were to complete all the evaluations in the study including who prematurely withdrew from the study. | Baseline (Baseline/Visit 1 for this study was the same as Final Visit/Visit 5 for completers of PR-04409.3) to Week 40 and Final Visit (Day closest to Day 281) | 
| Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE) | An adverse event is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal (investigational) product, whether or not related to medicinal (investigational) product. TEAE are defined as those AEs with onset date on or after the first dose date of study drug in Study PR-04509, or adverse events that worsen after the first dose date of study drug in Study PR-04509. | Up to Week 40 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postmenopausal Women, Vaginal Dryness, Postmenopausal Vulvovaginal Atrophy