Multicenter Study to Evaluate Safety and Efficacy of WC3011 (Estradiol Vaginal Cream) in Postmenopausal Women

Study Overview
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Brief Summary
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The primary objective of this study is to compare the efficacy of WC3011 with placebo vaginal gel in postmenopausal women for the relief of vaginal dryness caused by vaginal atrophy as measured by self-assessment, vaginal pH and vaginal smear.

Official Title
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A Randomized, Multicenter, Double-Blind, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of WC3011 in Postmenopausal Women

Conditions
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Vulvovaginal Atrophy

Intervention / Treatment
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* Drug: Vehicle
* Drug: WC3011 Estradiol Vaginal Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Moderate to severe vaginal dryness Postmenopausal meeting one of the following: 12 months spontaneous amenorrhea, 6 months spontaneous amenorrhea with serum Follicle-stimulating hormone (FSH) > 40 milli-International Unit (mIU)/mL, 6 weeks postsurgical bilateral oophorectomy confirmed by surgical report, ultrasound or serum FSH > 40 mIU/mL, 6 weeks postsurgical hysterectomy with ovary failure confirmed by serum FSH > 40 mIU/mL Age ≥ 40 years or if bilateral oophorectomy ≥ 35 years Vaginal pH >5.0 Less than or equal 5% superficial cells on vaginal wall cytologic smear Normal breast exam; if > 40 years, documentation of negative mammogram Exclusion Criteria: Randomization in PR-04409, participation in clinical trial or use of investigational drug within 30 days prior to screening Smokes ≥ 15 cigarettes/day Known or suspected premalignant or malignant disease Cardiovascular disease, insulin-dependent diabetes mellitus, congestive heart failure, stroke or ischemic attack, thrombophlebitis or thromboembolic disorder Increased frequency/severity headaches with estrogen therapy Drug addiction/alcohol abuse within last 2 years Currently taking St. John's Wort or anticoagulant Uncontrolled hypertension or thyroid disorder, clinically significant depression or untreated urinary tract infection

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vehicle (2 Times/Week)<br>Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks. | Drug: Vehicle<br>* Vehicle Cream applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks<br>|
| Placebo Comparator: WC3011 Estradiol Vaginal Cream (2 Times/Week)<br>WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks. | Drug: WC3011 Estradiol Vaginal Cream<br>* WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Final Assessment | Participant's self-assessment of Vaginal Dryness was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment. | Baseline (Day 0) to final assessment (Up to Week 12) | 
| Change From Baseline in Vaginal pH to Final Assessment | Vaginal pH was obtained at baseline and 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. Final assessment is defined as the last available postbaseline assessment. | Baseline (Day 0) to final assessment (Up to Week 12) | 
| Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | 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. A positive change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment. | Baseline (Day 0) to final assessment (Up to Week 12) | 
| Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | 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. A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment. | Baseline (Day 0) to final assessment (Up to Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Participant's self-assessment of Vaginal Dryness was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement. | Baseline (Day 0) to Weeks 2, 4, 8, and 12 | 
| Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Self-Assessment of the symptoms of VVA (vaginal and/or vulvar irritation/ Itching, dysuria, and dyspareunia) were evaluated by a questionnaire. Each symptom was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate, or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement. Final Assessment is defined as the last available post-baseline assessment for the given efficacy endpoint. | Baseline (Day 0) to Weeks 2, 4, 8, 12 and Final Assessment | 
| Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Vaginal bleeding associated with sexual activity was assessed by participants as either present or absent. Number of participants with assessment present are reported. Final assessment is defined as the last available postbaseline assessment. | Baseline (Day 0) and Weeks 2, 4, 8, 12 and Final Assessment | 
| Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | 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 each graded on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores are worse. A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment. | Baseline (Day 0) to Week 12 and Final Assessment | 
| Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | 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. A positive change from Baseline indicates improvement. | Baseline (Day 0) to Week 12 | 
| Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | 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. A negative change from Baseline indicates improvement. | Baseline (Day 0) to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaginal dryness, vaginal atrophy, estrogen