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

Study Overview
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Brief Summary
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The purpose of the study is to determine if WC3011 is safe and effective in treating the symptom of painful intercourse secondary to vulvovaginal atrophy as measured by participant self-assessment when compared to vehicle.

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 With Dyspareunia

Conditions
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Vulvovaginal Atrophy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sexually active with self-identified dyspareunia (pain with sexual activity), at least moderate to severe and most bothersome symptom of vulvovaginal atrophy (VVA) Postmenopausal and meets 1 of the following: 12 months spontaneous amenorrhea, 6 months spontaneous amenorrhea with FSH (follicle stimulating hormone) >40 mIU/mL,6 weeks postsurgical bilateral oophorectomy with confirmation by FSH >40 mIU/mL, surgical report or ultrasound, 6 weeks postsurgical hysterectomy with ovary failure confirmed by FSH >40 mIU/mL Age ≥40 years; ≥35 with bilateral oophorectomy Vaginal pH >5.0 Less than or equal to 5% superficial cells on vaginal wall cytologic smear Normal clinical breast exam or negative mammogram if ≥ 40 years of age Negative urine pregnancy test (non-hysterectomized and <12 months amenorrhea) Exclusion Criteria: Enrollment in Sponsor's Study PR-04409 or PR-05812 Participation in clinical trial or use of investigational drug within 30 days prior to screening Known hypersensitivity to estrogen and/or progestin therapy Known or suspected premalignant or malignant disease or history steroid-dependent malignancy Manifestation or treatment for significant cardiovascular disease (congestive heart failure, stroke or ischemic attack, myocardial infarction, coronary artery bypass, percutaneous angioplasty or >50% angiographic narrowing of coronary artery Thrombophlebitis or thromboembolic disorder or history of Insulin-dependent diabetes mellitus Increased frequency or severity of headaches while on hormone or estrogen therapy Currently taking St. John's Wort Drug/alcohol addiction within past 2 years Treatment with anticoagulants (heparin or warfarin) Smoking ≥15 cigarettes/day

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 |
| --- | --- |
| Active Comparator: Vehicle (3 Times/Week)<br>Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks. | Drug: Vehicle<br>* Daily for 14 days followed by 3 times per week for 10 weeks<br>|
| Experimental: WC3011 Estradiol Vaginal Cream (3 Times/Week)<br>WC3011 Estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks. | Drug: WC3011 Estradiol Vaginal Cream<br>* Daily for 14 days followed by 3 times per week for 10 weeks<br>* Other names: WC3011;|

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 Symptom of Vulvovaginal Atrophy (VVA): Dyspareunia (Pain Associated With Sexual Activity) to Final Assessment | Participant's self-assessment of the symptom of VVA (dyspareunia) was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher score indicates 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 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 post-baseline assessment for the given efficacy endpoint. | 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 the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Participant's self-assessment of the symptom of VVA (dyspareunia) was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher score indicates the most bothersome symptoms. A negative change from Baseline indicates improvement. | Baseline to Weeks 2, 4, 8 and 12 | 
| Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Self-Assessment of the symptoms of VVA, other than dyspareunia and vaginal bleeding associated with sexual activity, (vaginal and/or vulvar irritation/itching, dysuria and vaginal dryness) 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 (Up to Week 12) | 
| Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | 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 post-baseline assessment for the given efficacy endpoint. | Baseline (Day 0), Weeks 2, 4, 8, 12 and final assessment (Up to Week 12) | 
| 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 (Up to Week 12) | 
| Change From Baseline in Vaginal pH to Week 12 | 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. | Baseline to Week 12 | 
| 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 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 to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vulvovaginal Atrophy, Dyspareunia, Postmenopausal