Vulvovaginal Atrophy
Conditions
Keywords
Vulvovaginal Atrophy, Dyspareunia, Postmenopausal
Brief summary
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.
Interventions
Daily for 14 days followed by 3 times per week for 10 weeks
DRUGVehicle
Daily for 14 days followed by 3 times per 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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Participant's Self-Assessment of Symptom of Vulvovaginal Atrophy (VVA): Dyspareunia (Pain Associated With Sexual Activity) to Final Assessment | Baseline (Day 0) to final assessment (Up to Week 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. Final Assessment is defined as the last available post-baseline assessment for the given efficacy endpoint. |
| 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 post-baseline assessment for the given efficacy endpoint. |
| 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 Vaginal pH to Week 12 | Baseline 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. |
| Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Baseline 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. |
| Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Baseline 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 the Percentage of Vaginal Superficial Cells to Week 12 | Baseline 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 the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Baseline (Day 0) to Weeks 2, 4, 8, 12, and final assessment (Up to Week 12) | 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. |
| Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Baseline (Day 0), Weeks 2, 4, 8, 12 and final assessment (Up to Week 12) | 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. |
| 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 (Up to Week 12) | 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 (3 Times/Week) Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks. | 271 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks. | 277 |
| Total | 548 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 10 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Protocol Deviation | 7 | 4 |
| Overall Study | Reason not Specified | 2 | 1 |
| Overall Study | Withdrew Consent | 12 | 4 |
Baseline characteristics
| Characteristic | Vehicle (3 Times/Week) | WC3011 Estradiol Vaginal Cream (3 Times/Week) | Total |
|---|---|---|---|
| Age, Continuous | 58.6 years STANDARD_DEVIATION 6.1 | 58.7 years STANDARD_DEVIATION 6.4 | 58.6 years STANDARD_DEVIATION 6.3 |
| Sex: Female, Male Female | 271 Participants | 277 Participants | 548 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 / 271 | 0 / 277 |
| other Total, other adverse events | 42 / 271 | 38 / 277 |
| serious Total, serious adverse events | 1 / 271 | 3 / 277 |
Outcome results
Primary
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.
Time frame: Baseline (Day 0) to final assessment (Up to Week 12)
Population: Modified Intent-to-treat (mITT) Population included participants in the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of Symptom of Vulvovaginal Atrophy (VVA): Dyspareunia (Pain Associated With Sexual Activity) to Final Assessment | Baseline | 2.7 score on a scale | Standard Deviation 0.44 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of Symptom of Vulvovaginal Atrophy (VVA): Dyspareunia (Pain Associated With Sexual Activity) to Final Assessment | Change from Baseline to Final Assessment | -1.2 score on a scale | Standard Deviation 0.93 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of Symptom of Vulvovaginal Atrophy (VVA): Dyspareunia (Pain Associated With Sexual Activity) to Final Assessment | Baseline | 2.7 score on a scale | Standard Deviation 0.45 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of Symptom of Vulvovaginal Atrophy (VVA): Dyspareunia (Pain Associated With Sexual Activity) to Final Assessment | Change from Baseline to Final Assessment | -1.5 score on a scale | Standard Deviation 0.97 |
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 the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | Baseline | 50.6 percentage of parabasal cells | Standard Deviation 43.09 |
| Vehicle (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | Change From Baseline to Final Assessment | -14.6 percentage of parabasal cells | Standard Deviation 39.55 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | Baseline | 53.5 percentage of parabasal cells | Standard Deviation 42 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment | Change From Baseline to Final Assessment | -48.5 percentage of parabasal cells | Standard Deviation 45.11 |
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 the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | Baseline | 0.2 percentage of superficial cells | Standard Deviation 0.75 |
| Vehicle (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | Change from Baseline to Final Assessment | 1.4 percentage of superficial cells | Standard Deviation 6.08 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | Baseline | 0.2 percentage of superficial cells | Standard Deviation 0.7 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment | Change from Baseline to Final Assessment | 10.1 percentage of superficial cells | Standard Deviation 16.72 |
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 post-baseline assessment for the given efficacy endpoint.
Time frame: Baseline (Day 0) to final assessment (Up to Week 12)
Population: mITT Population included participants in the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Change From Baseline in Vaginal pH to Final Assessment | Baseline | 6.35 score on a scale | Standard Deviation 0.66 |
| Vehicle (3 Times/Week) | Change From Baseline in Vaginal pH to Final Assessment | Change from Baseline to Final Assessment | -0.53 score on a scale | Standard Deviation 0.92 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Vaginal pH to Final Assessment | Baseline | 6.37 score on a scale | Standard Deviation 0.66 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Vaginal pH to Final Assessment | Change from Baseline to Final Assessment | -1.36 score on a scale | Standard Deviation 0.89 |
Secondary
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.
Time frame: Baseline (Day 0) to Weeks 2, 4, 8, 12, and final assessment (Up to Week 12)
Population: mITT Population included participants in the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Week 12 | -0.6 score on a scale | Standard Deviation 0.95 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Week 8 | -0.2 score on a scale | Standard Deviation 0.73 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Week 4 | -0.5 score on a scale | Standard Deviation 0.94 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Week 12 | -0.2 score on a scale | Standard Deviation 0.78 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Final Assessment | -0.5 score on a scale | Standard Deviation 0.98 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Final Assessment | -0.2 score on a scale | Standard Deviation 0.8 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Week 2 | -0.3 score on a scale | Standard Deviation 0.94 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Baseline | 2.3 score on a scale | Standard Deviation 0.8 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Baseline | 0.4 score on a scale | Standard Deviation 0.74 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Week 2 | -0.6 score on a scale | Standard Deviation 1.08 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Week 8 | -0.5 score on a scale | Standard Deviation 0.98 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Week 4 | -0.8 score on a scale | Standard Deviation 0.96 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Week 8 | -0.9 score on a scale | Standard Deviation 0.98 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Week 2 | -0.1 score on a scale | Standard Deviation 0.82 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Week 12 | -0.9 score on a scale | Standard Deviation 0.98 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Baseline | 0.9 score on a scale | Standard Deviation 0.89 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Final Assessment | -0.8 score on a scale | Standard Deviation 0.98 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Week 4 | -0.2 score on a scale | Standard Deviation 0.76 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Final Assessment | -1.2 score on a scale | Standard Deviation 0.97 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Baseline | 1.0 score on a scale | Standard Deviation 0.89 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Week 2 | -0.3 score on a scale | Standard Deviation 0.94 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Week 4 | -0.3 score on a scale | Standard Deviation 0.96 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Week 8 | -0.4 score on a scale | Standard Deviation 0.97 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Week 12 | -0.4 score on a scale | Standard Deviation 0.96 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Itching-Change From Baseline to Final Assessment | -0.4 score on a scale | Standard Deviation 0.95 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Baseline | 0.4 score on a scale | Standard Deviation 0.72 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Week 2 | -0.1 score on a scale | Standard Deviation 0.77 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Week 4 | -0.1 score on a scale | Standard Deviation 0.8 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Week 8 | -0.2 score on a scale | Standard Deviation 0.76 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Week 12 | -0.2 score on a scale | Standard Deviation 0.75 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Dysuria-Change From Baseline to Final Assessment | -0.2 score on a scale | Standard Deviation 0.72 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Baseline | 2.3 score on a scale | Standard Deviation 0.73 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Week 2 | -0.7 score on a scale | Standard Deviation 1 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Week 8 | -1.1 score on a scale | Standard Deviation 0.91 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Week 12 | -1.2 score on a scale | Standard Deviation 0.94 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Other Symptoms of VVA to Weeks 2, 4, 8, 12, and Final Assessment | Vaginal Dryness-Change From Baseline to Week 4 | -0.9 score on a scale | Standard Deviation 0.91 |
Secondary
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.
Time frame: Baseline to Weeks 2, 4, 8 and 12
Population: mITT Population included participants in the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Change From Baseline to Week 2 | -0.8 score on a scale | Standard Deviation 0.87 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Change From Baseline to Week 8 | -1.2 score on a scale | Standard Deviation 0.92 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Change From Baseline to Week 4 | -1.1 score on a scale | Standard Deviation 0.93 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Change From Baseline to Week 12 | -1.2 score on a scale | Standard Deviation 0.9 |
| Vehicle (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Baseline | 2.7 score on a scale | Standard Deviation 0.44 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Change From Baseline to Week 12 | -1.5 score on a scale | Standard Deviation 0.95 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Baseline | 2.7 score on a scale | Standard Deviation 0.45 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Change From Baseline to Week 2 | -0.8 score on a scale | Standard Deviation 0.89 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Change From Baseline to Week 4 | -1.2 score on a scale | Standard Deviation 0.93 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Participant's Self-Assessment of the Symptom of VVA: Dyspareunia to Weeks 2, 4, 8, and 12 | Change From Baseline to Week 8 | -1.5 score on a scale | Standard Deviation 0.96 |
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 (Up to Week 12)
Population: mITT Population included participants in the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 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 | 1.8 score on a scale | Standard Deviation 0.68 |
| Vehicle (3 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 | -0.5 score on a scale | Standard Deviation 0.85 |
| Vehicle (3 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 | -0.5 score on a scale | Standard Deviation 0.83 |
| Vehicle (3 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 0.93 |
| Vehicle (3 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 | -0.6 score on a scale | Standard Deviation 0.95 |
| Vehicle (3 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 | -0.6 score on a scale | Standard Deviation 0.95 |
| Vehicle (3 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 | 0.7 score on a scale | Standard Deviation 0.83 |
| Vehicle (3 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 | -0.3 score on a scale | Standard Deviation 0.78 |
| Vehicle (3 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 | -0.3 score on a scale | Standard Deviation 0.78 |
| Vehicle (3 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 0.6 |
| Vehicle (3 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 | -0.5 score on a scale | Standard Deviation 0.75 |
| Vehicle (3 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 | -0.5 score on a scale | Standard Deviation 0.75 |
| Vehicle (3 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 | 1.8 score on a scale | Standard Deviation 0.69 |
| Vehicle (3 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 | -0.6 score on a scale | Standard Deviation 0.75 |
| Vehicle (3 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 | -0.6 score on a scale | Standard Deviation 0.75 |
| WC3011 Estradiol Vaginal Cream (3 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 | 1.8 score on a scale | Standard Deviation 0.75 |
| WC3011 Estradiol Vaginal Cream (3 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 0.85 |
| WC3011 Estradiol Vaginal Cream (3 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 | -0.9 score on a scale | Standard Deviation 0.94 |
| WC3011 Estradiol Vaginal Cream (3 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 | 1.8 score on a scale | Standard Deviation 0.7 |
| WC3011 Estradiol Vaginal Cream (3 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 | -0.9 score on a scale | Standard Deviation 0.95 |
| WC3011 Estradiol Vaginal Cream (3 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 0.64 |
| WC3011 Estradiol Vaginal Cream (3 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 | 1.2 score on a scale | Standard Deviation 0.99 |
| WC3011 Estradiol Vaginal Cream (3 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 0.85 |
| WC3011 Estradiol Vaginal Cream (3 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 | -1.0 score on a scale | Standard Deviation 0.99 |
| WC3011 Estradiol Vaginal Cream (3 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 | -0.9 score on a scale | Standard Deviation 0.84 |
| WC3011 Estradiol Vaginal Cream (3 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 | -1.0 score on a scale | Standard Deviation 0.97 |
| WC3011 Estradiol Vaginal Cream (3 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 0.84 |
| WC3011 Estradiol Vaginal Cream (3 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 0.89 |
| WC3011 Estradiol Vaginal Cream (3 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 | -0.9 score on a scale | Standard Deviation 0.83 |
| WC3011 Estradiol Vaginal Cream (3 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 0.86 |
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 to Week 12
Population: mITT Population included participants in the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Baseline | 50.6 percentage of parabasal cells | Standard Deviation 43.09 |
| Vehicle (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Change From Baseline to Week 12 | -14.9 percentage of parabasal cells | Standard Deviation 39.88 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Baseline | 53.5 percentage of parabasal cells | Standard Deviation 42 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 | Change From Baseline to Week 12 | -48.2 percentage of parabasal cells | Standard Deviation 45.65 |
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 to Week 12
Population: mITT Population included participants in the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | Baseline | 0.2 percentage of superficial cells | Standard Deviation 0.75 |
| Vehicle (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | Change From Baseline to Week 12 | 1.2 percentage of superficial cells | Standard Deviation 5.35 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | Change From Baseline to Week 12 | 10.5 percentage of superficial cells | Standard Deviation 17.19 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 | Baseline | 0.2 percentage of superficial cells | Standard Deviation 0.7 |
Secondary
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.
Time frame: Baseline to Week 12
Population: mITT Population included participants in the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Change From Baseline in Vaginal pH to Week 12 | Baseline | 6.35 score on a scale | Standard Deviation 0.66 |
| Vehicle (3 Times/Week) | Change From Baseline in Vaginal pH to Week 12 | Change From Baseline to Week 12 | -0.53 score on a scale | Standard Deviation 0.93 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Vaginal pH to Week 12 | Baseline | 6.37 score on a scale | Standard Deviation 0.66 |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Change From Baseline in Vaginal pH to Week 12 | Change From Baseline to Week 12 | -1.35 score on a scale | Standard Deviation 0.89 |
Secondary
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.
Time frame: Baseline (Day 0), Weeks 2, 4, 8, 12 and final assessment (Up to Week 12)
Population: mITT Population included participants in the Safety population who had at least 1 postbaseline primary efficacy assessment and met all of the following inclusion criteria: ≤5% superficial cells on a vaginal wall smear, a vaginal pH \>5.0, and the participants most bothersome symptom of VVA was dyspareunia 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 (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Baseline | 27.0 percentage of participants |
| Vehicle (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Week 2 | 15.9 percentage of participants |
| Vehicle (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Week 4 | 7.9 percentage of participants |
| Vehicle (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Week 8 | 10.8 percentage of participants |
| Vehicle (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Week 12 | 12.1 percentage of participants |
| Vehicle (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Final Assessment | 14.4 percentage of participants |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Week 12 | 7.5 percentage of participants |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Baseline | 28.0 percentage of participants |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Week 8 | 6.7 percentage of participants |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Week 2 | 16.4 percentage of participants |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Final Assessment | 6.5 percentage of participants |
| WC3011 Estradiol Vaginal Cream (3 Times/Week) | Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit | Week 4 | 7.2 percentage of participants |