A Safety and Efficacy Study of Estradiol Vaginal Capsule in Postmenopausal Women With Vulvovaginal Atrophy

Study Overview
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Brief Summary
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This study will access the safety and efficacy of three doses of estradiol vaginal capsules in postmenopausal women with vulvovaginal atrophy.

Official Title
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A Phase 2, Randomized, Multicenter, Double-blind, Vehicle-controlled Study to Evaluate Safety and Efficacy of Three Doses of Estradiol Vaginal Capsule in Postmenopausal Women With Vulvovaginal Atrophy

Conditions
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Vulvovaginal Atrophy, Menopause, Dyspareunia

Intervention / Treatment
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* Drug: Estradiol Vaginal Capsule (EVC)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of vulvovaginal atrophy due to post menopause Age ≥ 40 years or if bilateral oophorectomy ≥ 35 years Moderate to severe vaginal dryness Normal breast exam; if > 40 years Vaginal pH > 5.0 < 5% superficial cells on vaginal wall cytology smear Exclusion Criteria: Known hypersensitivity to estrogen and/or progestin therapy Known or suspected premalignant or malignant disease Undiagnosed abnormal genital bleeding A history of or treatment for significant cardiovascular disease, congestive heart failure, or stroke Active or known protein C, protein S, or antithrombin deficient, or other known thrombophilic disorders or thromboembolic events Increased frequency/severity headaches with estrogen therapy Smokes ≥ 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Estradiol Vaginal Capsule 0.003 mg<br>Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks | Drug: Estradiol Vaginal Capsule (EVC)<br>* Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks<br>|
| Experimental: Estradiol Vaginal Capsule 0.01 mg<br>Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks | Drug: Estradiol Vaginal Capsule (EVC)<br>* Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks<br>|
| Experimental: Estradiol Vaginal Capsule 0.02 mg<br>Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks | Drug: Estradiol Vaginal Capsule (EVC)<br>* Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks<br>|
| Placebo Comparator: Placebo<br>Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks | Drug: Placebo<br>* Administered intravaginally once daily for 2 weeks and then once weekly for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the percentage of vaginal superficial cells |  | Baseline (Week 0) to Final Visit (Week 6) | 
| Change in the percentage of vaginal parabasal cells |  | Baseline (Week 0) to Final Visit (Week 6) | 
| Change in vaginal pH |  | Baseline (Week 0) to Final Visit (Week 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the investigator assessment of VVA measured by scoring the vaginal health in 5 categories using a 4-point scale | Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3. | Baseline (Week 0) to Final Visit (Week 6) | 
| Change in subject's self-assessment of vaginal dryness reported as the most bothersome symptom | Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3. | Baseline (Week 0) to Final Visit (Week 6) | 
| Change in subject's self-assessment of dyspareunia reported as the most bothersome symptom | Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3. | Baseline (Week 0) to Final Visit (Week 6) | 
| Change in subject's self-assessment of dysuria | Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3. | Baseline (Week 0) to Final Visit (Week 6) | 
| Change in subject's self-assessment of vaginal and/or vulvar irritation/itching | Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3. | Baseline (Week 0) to Final Visit (Week 6) | 
| Change in subject's self-assessment of vaginal dryness in patients where vaginal dryness was not reported as the most bothersome symptom | Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3. | Baseline (Week 0) to Final Visit (Week 6) | 
| Change in subject's self-assessment of dyspareunia in patients where dyspareunia was not reported as the most bothersome symptom | Outcome was measured by using a 4-point severity scale with: None=0, Mild=1, Moderate=2, and Severe=3. | Baseline (Week 0) to Final Visit (Week 6) | 
| Self-assessment by sexually active participants as to the presence or absence of vaginal bleeding | Total number of participants who were sexually active assessed if vaginal bleeding was present or absent. | Baseline (Week 0) to Final Visit (Week 6) |