Vulvovaginal Atrophy
Conditions
Keywords
vaginal dryness, vaginal atrophy, estrogen
Brief summary
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.
Interventions
DRUGVehicle
Vehicle Cream applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks
WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks
Sponsors
Warner Chilcott
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
35 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Final Assessment | Baseline (Day 0) to final assessment (Up to Week 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. Final assessment is defined as the last available postbaseline assessment. |
| Change From Baseline in Vaginal pH to Final Assessment | Baseline (Day 0) to final assessment (Up 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. Final assessment is defined as the last available postbaseline assessment. |
| Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | Baseline (Day 0) to final assessment (Up 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. Final assessment is defined as the last available postbaseline assessment. |
| Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | Baseline (Day 0) to final assessment (Up 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. Final assessment is defined as the last available postbaseline assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | Baseline (Day 0) 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. |
| Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Baseline (Day 0) 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. |
| Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Baseline (Day 0) 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. |
| Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Baseline (Day 0) to Weeks 2, 4, 8, 12 and Final Assessment | 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. |
| Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Baseline (Day 0) and Weeks 2, 4, 8, 12 and Final Assessment | 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. |
| Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Baseline (Day 0) 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vehicle (2 Times/Week) Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks. | 287 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks. | 286 |
| Total | 573 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 8 |
| Overall Study | Lack of Efficacy | 1 | 2 |
| Overall Study | Lost to Follow-up | 5 | 3 |
| Overall Study | Protocol Violation | 6 | 3 |
| Overall Study | Reason not Specified | 4 | 2 |
| Overall Study | Withdrew Consent | 6 | 4 |
Baseline characteristics
| Characteristic | Vehicle (2 Times/Week) | WC3011 Estradiol Vaginal Cream (2 Times/Week) | Total |
|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 6.1 | 59.5 years STANDARD_DEVIATION 6.7 | 59.6 years STANDARD_DEVIATION 6.4 |
| Sex: Female, Male Female | 287 Participants | 286 Participants | 573 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 287 | 0 / 286 |
| other Total, other adverse events | 35 / 287 | 38 / 286 |
| serious Total, serious adverse events | 2 / 287 | 2 / 286 |
Outcome results
Primary
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.
Time frame: Baseline (Day 0) to final assessment (Up to Week 12)
Population: Modified Intent-to-Treat (mITT) Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Final Assessment | Baseline | 2.5 score on a scale | Standard Deviation 0.5 |
| Vehicle (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Final Assessment | Change from Baseline to Final Assessment | -1.2 score on a scale | Standard Deviation 0.92 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Final Assessment | Baseline | 2.5 score on a scale | Standard Deviation 0.5 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Final Assessment | Change from Baseline to Final Assessment | -1.4 score on a scale | Standard Deviation 0.94 |
Primary
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.
Time frame: Baseline (Day 0) to final assessment (Up to Week 12)
Population: mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | Baseline | 46.5 percentage of parabasal cells | Standard Deviation 44.81 |
| Vehicle (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | Change from Baseline to Final Assessment | -4.4 percentage of parabasal cells | Standard Deviation 42.93 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | Baseline | 44.2 percentage of parabasal cells | Standard Deviation 42.29 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | Change from Baseline to Final Assessment | -37.4 percentage of parabasal cells | Standard Deviation 42.62 |
Primary
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.
Time frame: Baseline (Day 0) to final assessment (Up to Week 12)
Population: mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | Baseline | 0.3 percentage of superficial cells | Standard Deviation 1.05 |
| Vehicle (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | Change from Baseline to Final Assessment | 0.8 percentage of superficial cells | Standard Deviation 5.68 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | Baseline | 0.4 percentage of superficial cells | Standard Deviation 1.13 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | Change from Baseline to Final Assessment | 8.6 percentage of superficial cells | Standard Deviation 14.49 |
Primary
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.
Time frame: Baseline (Day 0) to final assessment (Up to Week 12)
Population: mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle (2 Times/Week) | Change From Baseline in Vaginal pH to Final Assessment | Baseline | 6.33 score on a scale | Standard Deviation 0.65 |
| Vehicle (2 Times/Week) | Change From Baseline in Vaginal pH to Final Assessment | Change from Baseline to Final Assessment | -0.31 score on a scale | Standard Deviation 0.8 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Vaginal pH to Final Assessment | Baseline | 6.34 score on a scale | Standard Deviation 0.65 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Vaginal pH to Final Assessment | Change from Baseline to Final Assessment | -1.26 score on a scale | Standard Deviation 0.99 |
Secondary
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.
Time frame: Baseline (Day 0) to Weeks 2, 4, 8, and 12
Population: mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Change from Baseline to Week 2 | -0.9 score on a scale | Standard Deviation 0.92 |
| Vehicle (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Change from Baseline to Week 8 | -1.2 score on a scale | Standard Deviation 0.87 |
| Vehicle (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Change from Baseline to Week 4 | -1.1 score on a scale | Standard Deviation 0.87 |
| Vehicle (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Change from Baseline to Week 12 | -1.2 score on a scale | Standard Deviation 0.9 |
| Vehicle (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Baseline | 2.5 score on a scale | Standard Deviation 0.5 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Change from Baseline to Week 12 | -1.5 score on a scale | Standard Deviation 0.93 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Baseline | 2.5 score on a scale | Standard Deviation 0.5 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Change from Baseline to Week 2 | -1.0 score on a scale | Standard Deviation 0.94 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Change from Baseline to Week 4 | -1.2 score on a scale | Standard Deviation 0.86 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 | Change from Baseline to Week 8 | -1.4 score on a scale | Standard Deviation 0.85 |
Secondary
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.
Time frame: Baseline (Day 0) to Weeks 2, 4, 8, 12 and Final Assessment
Population: mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Baseline | 1.1 score on a scale | Standard Deviation 0.97 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Week 2 | -0.5 score on a scale | Standard Deviation 0.93 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Week 4 | -0.6 score on a scale | Standard Deviation 0.99 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Week 8 | -0.6 score on a scale | Standard Deviation 0.95 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Week 12 | -0.7 score on a scale | Standard Deviation 1 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Final Assessment | -0.7 score on a scale | Standard Deviation 0.99 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Baseline | 0.3 score on a scale | Standard Deviation 0.66 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Week 2 | -0.1 score on a scale | Standard Deviation 0.71 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Week 4 | -0.1 score on a scale | Standard Deviation 0.75 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Week 8 | -0.2 score on a scale | Standard Deviation 0.65 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Week 12 | -0.2 score on a scale | Standard Deviation 0.65 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Final Assessment | -0.2 score on a scale | Standard Deviation 0.64 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Baseline | 2.1 score on a scale | Standard Deviation 0.92 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Week 2 | -0.7 score on a scale | Standard Deviation 0.91 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Week 4 | -1.0 score on a scale | Standard Deviation 0.9 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Week 8 | -0.9 score on a scale | Standard Deviation 0.99 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Week 12 | -1.1 score on a scale | Standard Deviation 0.97 |
| Vehicle (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Final Assessment | -1.0 score on a scale | Standard Deviation 0.95 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Week 2 | -0.7 score on a scale | Standard Deviation 1.04 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Baseline | 1.1 score on a scale | Standard Deviation 0.97 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Week 8 | -0.2 score on a scale | Standard Deviation 0.75 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Week 2 | -0.5 score on a scale | Standard Deviation 0.95 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Final Assessment | -1.1 score on a scale | Standard Deviation 1.11 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Week 4 | -0.6 score on a scale | Standard Deviation 0.89 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Week 12 | -0.2 score on a scale | Standard Deviation 0.69 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Week 8 | -0.6 score on a scale | Standard Deviation 0.92 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Week 4 | -1.1 score on a scale | Standard Deviation 1.05 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Week 12 | -0.7 score on a scale | Standard Deviation 0.94 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Final Assessment | -0.2 score on a scale | Standard Deviation 0.71 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Vaginal Itching - Change from Baseline to Final Assessment | -0.6 score on a scale | Standard Deviation 0.99 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Week 12 | -1.1 score on a scale | Standard Deviation 1.12 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Baseline | 0.4 score on a scale | Standard Deviation 0.72 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Baseline | 2.1 score on a scale | Standard Deviation 0.99 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Week 2 | -0.2 score on a scale | Standard Deviation 0.66 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dyspareunia - Change from Baseline to Week 8 | -1.2 score on a scale | Standard Deviation 1.03 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in Participants Self-Assessment of the Symptoms of VVA | Dysuria - Change from Baseline to Week 4 | -0.2 score on a scale | Standard Deviation 0.69 |
Secondary
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.
Time frame: Baseline (Day 0) to Week 12 and Final Assessment
Population: mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Pallor - Change from Baseline to Week 12 | -0.4 score on a scale | Standard Deviation 0.79 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Dryness - Change from Baseline to Final Assessment | -0.6 score on a scale | Standard Deviation 0.84 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Atrophy - Change from Baseline to Week 12 | -0.4 score on a scale | Standard Deviation 0.74 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Friability - Baseline | 1.1 score on a scale | Standard Deviation 0.86 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Pallor - Change from Baseline to Final Assessment | -0.4 score on a scale | Standard Deviation 0.79 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Friability - Change from Baseline to Week 12 | -0.5 score on a scale | Standard Deviation 0.81 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Pallor - Baseline | 1.9 score on a scale | Standard Deviation 0.67 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Friability - Change from Baseline to Final Assessment | -0.5 score on a scale | Standard Deviation 0.81 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Dryness - Baseline | 2.0 score on a scale | Standard Deviation 0.65 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Petechiae - Baseline | 0.8 score on a scale | Standard Deviation 0.86 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Atrophy - Change from Baseline to Final Assessment | -0.4 score on a scale | Standard Deviation 0.74 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Petechiae - Change from Baseline to Week 12 | -0.4 score on a scale | Standard Deviation 0.71 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Dryness - Change from Baseline to Week 12 | -0.6 score on a scale | Standard Deviation 0.84 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Petechiae - Change from Baseline to Final Assessment | -0.4 score on a scale | Standard Deviation 0.74 |
| Vehicle (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Atrophy - Baseline | 2.1 score on a scale | Standard Deviation 0.6 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Petechiae - Change from Baseline to Final Assessment | -0.6 score on a scale | Standard Deviation 0.83 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Atrophy - Baseline | 2.0 score on a scale | Standard Deviation 0.65 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Atrophy - Change from Baseline to Week 12 | -0.7 score on a scale | Standard Deviation 0.8 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Atrophy - Change from Baseline to Final Assessment | -0.7 score on a scale | Standard Deviation 0.79 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Pallor - Baseline | 1.9 score on a scale | Standard Deviation 0.66 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Pallor - Change from Baseline to Week 12 | -0.9 score on a scale | Standard Deviation 0.79 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Pallor - Change from Baseline to Final Assessment | -0.9 score on a scale | Standard Deviation 0.82 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Dryness - Baseline | 2.0 score on a scale | Standard Deviation 0.69 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Dryness - Change from Baseline to Week 12 | -1.1 score on a scale | Standard Deviation 0.89 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Dryness - Change from Baseline to Final Assessment | -1.1 score on a scale | Standard Deviation 0.89 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Friability - Baseline | 1.1 score on a scale | Standard Deviation 0.86 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Friability - Change from Baseline to Week 12 | -0.8 score on a scale | Standard Deviation 0.92 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Friability - Change from Baseline to Final Assessment | -0.8 score on a scale | Standard Deviation 0.92 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Petechiae - Baseline | 0.8 score on a scale | Standard Deviation 0.82 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment | Petechiae - Change from Baseline to Week 12 | -0.6 score on a scale | Standard Deviation 0.82 |
Secondary
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.
Time frame: Baseline (Day 0) to Week 12
Population: mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Baseline | 46.5 percentage of parabasal cells | Standard Deviation 44.81 |
| Vehicle (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Change from Baseline to Week 12 | -4.7 percentage of parabasal cells | Standard Deviation 43.39 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Baseline | 44.2 percentage of parabasal cells | Standard Deviation 42.29 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Change from Baseline to Week 12 | -38.7 percentage of parabasal cells | Standard Deviation 41.58 |
Secondary
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.
Time frame: Baseline (Day 0) to Week 12
Population: mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vehicle (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | Baseline | 0.3 percentage of superficial cells | Standard Deviation 1.05 |
| Vehicle (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | Change from Baseline to Week 12 | 0.6 percentage of superficial cells | Standard Deviation 3.35 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | Baseline | 0.4 percentage of superficial cells | Standard Deviation 1.13 |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | Change from Baseline to Week 12 | 9.3 percentage of superficial cells | Standard Deviation 14.87 |
Secondary
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.
Time frame: Baseline (Day 0) and Weeks 2, 4, 8, 12 and Final Assessment
Population: mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vehicle (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Baseline | 18.5 percentage of participants |
| Vehicle (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Week 2 | 8.4 percentage of participants |
| Vehicle (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Week 4 | 6.1 percentage of participants |
| Vehicle (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Week 8 | 8.0 percentage of participants |
| Vehicle (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Week 12 | 6.6 percentage of participants |
| Vehicle (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Final Assessment | 7.9 percentage of participants |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Week 12 | 3.8 percentage of participants |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Baseline | 24.3 percentage of participants |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Week 8 | 6.7 percentage of participants |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Week 2 | 8.4 percentage of participants |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Final Assessment | 5.1 percentage of participants |
| WC3011 Estradiol Vaginal Cream (2 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity | Week 4 | 4.6 percentage of participants |