Safety & Efficacy WC3011 (Estradiol Vaginal Cream) in the Treatment of Vulvovaginal Atrophy in Postmenopausal Women

Study Overview
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Brief Summary
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Study if WC3011 is effective and safe in the treatment of postmenopausal vaginal dryness due to vulvovaginal atrophy.

Official Title
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A Randomized, Double-Blind, Vehicle-Controlled Study of the Safety and Efficacy of WC3011 (Estradiol Vaginal Cream) in the Treatment of Symptoms of Vulvovaginal Atrophy in Postmenopausal Women

Conditions
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Postmenopausal 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: Postmenopausal females ≥35 years with either or both ovaries removed or naturally menopausal with moderate to severe vaginal dryness Exclusion Criteria: 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, congestive heart failure, stroke or ischemic attacks Insulin-dependent diabetes mellitus Increased frequency or severity of headaches while on hormone or estrogen therapy Drug or alcohol addiction within last 2 years Participation in a clinical trial within 30 days Smoking ≥ 15 cigarettes daily Uncontrolled hypertension - systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 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 administered once daily for 2 weeks followed by 2X/week or 3X/week for 10 weeks, total treatment duration 12 weeks<br>|
| Placebo Comparator: Vehicle (2 Times/Week)<br>Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks. | Drug: Vehicle<br>* Vehicle administered once daily for 2 weeks followed by 2X/week or 3X/week for 10 weeks, total treatment duration 12 weeks.<br>|
| Experimental: WC3011 Estradiol Vaginal Cream (3 Times/Week)<br>WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks. | Drug: WC3011 Estradiol Vaginal Cream<br>* WC3011 estradiol vaginal cream administered once daily for 2 weeks followed by 2X/week or 3X/week for 10 weeks, total treatment duration 12 weeks<br>|
| Placebo Comparator: Vehicle (3 Times/Week)<br>Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks. | Drug: Vehicle<br>* Vehicle administered once daily for 2 weeks followed by 2X/week or 3X/week for 10 weeks, total treatment duration 12 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 Week 12/Final Visit | The severity of vaginal dryness was assessed and recorded on a questionnaire by the participants using the following 4 point scale where, 0=None (The symptom is not present), 1=Mild (The symptom is present but may be intermittent; does not interfere with participants activities or lifestyle), 2=Moderate (The symptom is present. Participant is usually aware of the symptom, but activities and lifestyle are only occasionally affected), and 3=Severe (The symptom is present. Participant is usually aware and bothered by the symptom and have modified participant's activities and/or lifestyle due to the symptom. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Week 12/Final Visit | 
| Change From Baseline in Vaginal pH to Week 12/Final Visit | Vaginal pH was obtained at final visit of the study. The pH was a numeric value from a scale of 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. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Week 12/Final Visit | 
| Change From Baseline in Percentage of Vaginal Superficial Cells to Week 12/Final Visit | 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. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Week 12/Final Visit | 
| Change From Baseline in Percentage of Vaginal Parabasal Cells to Week 12/Final Visit | 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. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Week 12/Final Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Investigator's Assessment of Atrophy to Week 12 and Week 12/Final Visit | Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to atrophy scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Week 12 and Week 12/Final visit | 
| Change From Baseline in Investigator's Assessment of Pallor to Week 12 and Week 12/Final Visit | Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to pallor scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Week 12 and Week 12/Final visit | 
| Change From Baseline in Investigator's Assessment of Vaginal Dryness to Week 12 and Week 12/Final Visit | Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to vaginal dryness scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Week 12 and Week 12/Final visit | 
| Change From Baseline in Investigator's Assessment of Friability to Week 12 and Week 12/Final Visit | Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to friability scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Week 12 and Week 12/Final visit | 
| Change From Baseline in Investigator's Assessment of Petechiae to Week 12 and Week 12/Final Visit | Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to petechiae scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Week 12 and Week 12/Final visit | 
| 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 symptoms of VVA (severity of vaginal dryness) was scored according to a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. | Baseline (Day 0) to Weeks 2, 4, 8 and 12 | 
| Change From Baseline in Participant's Self-Assessment of Vaginal and/or Vulvar Irritation/Itching to Weeks 2, 4, 8, 12 and Week 12/Final Visit | Participant's self-assessment of symptoms of VVA (vaginal and/or vulvar irritation/itching) was scored according to a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Weeks 2, 4, 8, 12 and Week 12/Final visit | 
| Change From Baseline in Participant's Self-Assessment of Dysuria (Painful or Difficult Urination) to Weeks 2, 4, 8, 12 and Week 12/Final Visit | Participant's self-assessment of symptoms of VVA (dysuria) was scored according to a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Weeks 2, 4, 8, 12 and Week 12/Final visit | 
| Change From Baseline in Participant's Self-Assessment of Dyspareunia (Pain Associated With Sexual Activity) to Weeks 2, 4, 8, 12 and Week 12/Final Visit | Participant's self-assessment of symptoms of VVA (dyspareunia) was scored according to a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) to Weeks 2, 4, 8, 12 and Week 12/Final visit | 
| Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity as Per Participant's Self-Assessment to Weeks 2, 4, 8, 12 and Week 12/Final Visit | Vaginal bleeding associated with sexual activity was assessed by participants as either present or absent. Percentage of participants with assessment present are reported. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12. | Baseline (Day 0) and Weeks 2, 4, 8, 12 and Week 12/Final visit | 
| Change From Baseline in Vaginal pH to Week 12 | Vaginal pH was obtained at final visit of the study. The pH was a numeric value from a scale of 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 (Day 0) to Week 12 | 
| Change From Baseline in 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. | Baseline (Day 0) to Week 12 | 
| Change From Baseline in 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. | 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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Postmenopausal Women, Vaginal Dryness