Trial Outcomes & Findings for Study to Evaluate Safety and Efficacy of WC3011 (Estradiol Vaginal Cream) in Postmenopausal Women With Dyspareunia (NCT NCT01845649)

Last Updated: 2022-05-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

550 participants

Primary outcome timeframe

Baseline (Day 0) to final assessment (Up to Week 12)

Results posted on

2022-05-09

Participant Flow

Participant milestones

Participant milestones
Measure	Vehicle (3 Times/Week) Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	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.
Overall Study STARTED	273	277
Overall Study Safety Population	271	277
Overall Study Modified Intent-to-treat (mITT) Population	233	239
Overall Study COMPLETED	242	255
Overall Study NOT COMPLETED	31	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Vehicle (3 Times/Week) Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	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.
Overall Study Adverse Event	7	10
Overall Study Lack of Efficacy	1	1
Overall Study Lost to Follow-up	2	2
Overall Study Withdrew Consent	12	4
Overall Study Protocol Deviation	7	4
Overall Study Reason not Specified	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vehicle (3 Times/Week) n=271 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=277 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.	Total n=548 Participants Total of all reporting groups
Age, Continuous	58.6 years STANDARD_DEVIATION 6.1 • n=5 Participants	58.7 years STANDARD_DEVIATION 6.4 • n=7 Participants	58.6 years STANDARD_DEVIATION 6.3 • n=5 Participants
Sex: Female, Male Female	271 Participants n=5 Participants	277 Participants n=7 Participants	548 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
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	2.7 score on a scale Standard Deviation 0.45
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	-1.5 score on a scale Standard Deviation 0.97

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
Change From Baseline in Vaginal pH to Final Assessment Baseline	6.35 score on a scale Standard Deviation 0.66	6.37 score on a scale Standard Deviation 0.66
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	-1.36 score on a scale Standard Deviation 0.89

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment Baseline	0.2 percentage of superficial cells Standard Deviation 0.75	0.2 percentage of superficial cells Standard Deviation 0.70
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	10.1 percentage of superficial cells Standard Deviation 16.72

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment Baseline	50.6 percentage of parabasal cells Standard Deviation 43.09	53.5 percentage of parabasal cells Standard Deviation 42.00
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	-48.5 percentage of parabasal cells Standard Deviation 45.11

SECONDARY outcome

Timeframe: Baseline to Weeks 2, 4, 8 and 12

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
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	2.7 score on a scale Standard Deviation 0.45
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	-0.8 score on a scale Standard Deviation 0.89
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	-1.2 score on a scale Standard Deviation 0.93
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	-1.5 score on a scale Standard Deviation 0.96
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 0.90	-1.5 score on a scale Standard Deviation 0.95

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
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	1.0 score on a scale Standard Deviation 0.89
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	-0.3 score on a scale Standard Deviation 0.94
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	-0.3 score on a scale Standard Deviation 0.96
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	-0.4 score on a scale Standard Deviation 0.97
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	-0.4 score on a scale Standard Deviation 0.96
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	-0.4 score on a scale Standard Deviation 0.95
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	0.4 score on a scale Standard Deviation 0.72
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	-0.1 score on a scale Standard Deviation 0.77
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	-0.1 score on a scale Standard Deviation 0.80
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	-0.2 score on a scale Standard Deviation 0.76
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	-0.2 score on a scale Standard Deviation 0.75
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 0.80	-0.2 score on a scale Standard Deviation 0.72
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 0.80	2.3 score on a scale Standard Deviation 0.73
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	-0.7 score on a scale Standard Deviation 1.00
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	-0.9 score on a scale Standard Deviation 0.91
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	-1.1 score on a scale Standard Deviation 0.91
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	-1.2 score on a scale Standard Deviation 0.94
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	-1.2 score on a scale Standard Deviation 0.97

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit Baseline	27.0 percentage of participants	28.0 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit Week 2	15.9 percentage of participants	16.4 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit Week 4	7.9 percentage of participants	7.2 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit Week 8	10.8 percentage of participants	6.7 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit Week 12	12.1 percentage of participants	7.5 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity at Each Visit Final Assessment	14.4 percentage of participants	6.5 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
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 0.60	2.0 score on a scale Standard Deviation 0.64
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	-0.9 score on a scale Standard Deviation 0.84
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	-0.9 score on a scale Standard Deviation 0.83
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	1.8 score on a scale Standard Deviation 0.70
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	-0.9 score on a scale Standard Deviation 0.84
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	-0.9 score on a scale Standard Deviation 0.85
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	1.8 score on a scale Standard Deviation 0.75
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	-0.9 score on a scale Standard Deviation 0.94
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	-0.9 score on a scale Standard Deviation 0.95
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	1.2 score on a scale Standard Deviation 0.99
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	-1.0 score on a scale Standard Deviation 0.99
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	-1.0 score on a scale Standard Deviation 0.97
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	0.8 score on a scale Standard Deviation 0.89
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	-0.6 score on a scale Standard Deviation 0.86
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	-0.6 score on a scale Standard Deviation 0.85

SECONDARY outcome

Timeframe: Baseline to Week 12

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
Change From Baseline in Vaginal pH to Week 12 Baseline	6.35 score on a scale Standard Deviation 0.66	6.37 score on a scale Standard Deviation 0.66
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	-1.35 score on a scale Standard Deviation 0.89

SECONDARY outcome

Timeframe: Baseline to Week 12

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 Baseline	0.2 percentage of superficial cells Standard Deviation 0.75	0.2 percentage of superficial cells Standard Deviation 0.70
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	10.5 percentage of superficial cells Standard Deviation 17.19

SECONDARY outcome

Timeframe: Baseline to Week 12

Outcome measures

Outcome measures
Measure	Vehicle (3 Times/Week) n=233 Participants Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=239 Participants WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 Baseline	50.6 percentage of parabasal cells Standard Deviation 43.09	53.5 percentage of parabasal cells Standard Deviation 42.00
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	-48.2 percentage of parabasal cells Standard Deviation 45.65

Adverse Events

Vehicle (3 Times/Week)

Serious events: 1 serious events

Other events: 42 other events

Deaths: 0 deaths

WC3011 Estradiol Vaginal Cream (3 Times/Week)

Serious events: 3 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vehicle (3 Times/Week) n=271 participants at risk Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=277 participants at risk WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
Cardiac disorders Atrial Fibrillation	0.37% 1/271 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.	0.00% 0/277 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.
Infections and infestations Appendicitis	0.00% 0/271 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.	0.36% 1/277 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.
Injury, poisoning and procedural complications Accidental Overdose	0.00% 0/271 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.	0.36% 1/277 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain Neoplasm	0.00% 0/271 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.	0.36% 1/277 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.
Vascular disorders Deep vein thrombosis	0.00% 0/271 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.	0.36% 1/277 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure	Vehicle (3 Times/Week) n=271 participants at risk Vehicle applied to the vagina daily for 14 days followed by dosing 3 times per week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=277 participants at risk WC3011 estradiol vaginal cream applied daily for 14 days followed by dosing 3 times per week for 10 weeks.
Infections and infestations Urinary tract infection	7.7% 21/271 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.	3.6% 10/277 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.
General disorders Application site pain	5.5% 15/271 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.	3.2% 9/277 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.
Infections and infestations Vulvovaginal mycotic infection	3.3% 9/271 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.	6.9% 19/277 • Up to Week 12 Safety population included participants who were randomized into the study and took at least 1 dose of study drug.

Additional Information

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER