Trial Outcomes & Findings for Safety & Efficacy WC3011 (Estradiol Vaginal Cream) in the Treatment of Vulvovaginal Atrophy in Postmenopausal Women (NCT NCT01400776)

NCT ID: NCT01400776

Last Updated: 2022-05-09

Results Overview

The severity of vaginal dryness was assessed and recorded on a questionnaire by the participants using the following 4 point scale where, 0=None (The symptom is not present), 1=Mild (The symptom is present but may be intermittent; does not interfere with participants activities or lifestyle), 2=Moderate (The symptom is present. Participant is usually aware of the symptom, but activities and lifestyle are only occasionally affected), and 3=Severe (The symptom is present. Participant is usually aware and bothered by the symptom and have modified participant's activities and/or lifestyle due to the symptom. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 722 participants
• Primary outcome timeframe: Baseline (Day 0) to Week 12/Final Visit
• Results posted on: 2022-05-09

Participant Flow

Participant milestones

Measure	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.	Vehicle (2 Times/Week) Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Overall Study STARTED	238	124	237	123
Overall Study COMPLETED	217	119	209	114
Overall Study NOT COMPLETED	21	5	28	9

Reasons for withdrawal

Measure	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.	Vehicle (2 Times/Week) Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Overall Study Adverse Event	7	2	9	2
Overall Study Lost to Follow-up	1	0	4	1
Overall Study Withdrew Consent	4	2	6	1
Overall Study Protocol Deviation	6	1	5	2
Overall Study Reason not Specified	3	0	4	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=238 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=124 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=237 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Total n=722 Participants Total of all reporting groups
Age, Continuous	58.4 years STANDARD_DEVIATION 6.27 • n=5 Participants	57.8 years STANDARD_DEVIATION 6.34 • n=7 Participants	58.0 years STANDARD_DEVIATION 6.03 • n=5 Participants	58.7 years STANDARD_DEVIATION 6.58 • n=4 Participants	58.2 years STANDARD_DEVIATION 6.26 • n=21 Participants
Sex: Female, Male Female	238 Participants n=5 Participants	124 Participants n=7 Participants	237 Participants n=5 Participants	123 Participants n=4 Participants	722 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants	10 Participants n=4 Participants	45 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	224 Participants n=5 Participants	118 Participants n=7 Participants	222 Participants n=5 Participants	113 Participants n=4 Participants	677 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Black or African American	29 Participants n=5 Participants	18 Participants n=7 Participants	27 Participants n=5 Participants	14 Participants n=4 Participants	88 Participants n=21 Participants
Race (NIH/OMB) White	202 Participants n=5 Participants	105 Participants n=7 Participants	208 Participants n=5 Participants	106 Participants n=4 Participants	621 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) to Week 12/Final Visit

Population: Modified Intent-to-Treat Population (mITT) included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

The severity of vaginal dryness was assessed and recorded on a questionnaire by the participants using the following 4 point scale where, 0=None (The symptom is not present), 1=Mild (The symptom is present but may be intermittent; does not interfere with participants activities or lifestyle), 2=Moderate (The symptom is present. Participant is usually aware of the symptom, but activities and lifestyle are only occasionally affected), and 3=Severe (The symptom is present. Participant is usually aware and bothered by the symptom and have modified participant's activities and/or lifestyle due to the symptom. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Week 12/Final Visit Baseline	2.49 score on a scale Standard Deviation 0.50	2.46 score on a scale Standard Deviation 0.52	2.50 score on a scale Standard Deviation 0.50	2.50 score on a scale Standard Deviation 0.50
Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-1.27 score on a scale Standard Deviation 0.90	-0.99 score on a scale Standard Deviation 0.89	-1.31 score on a scale Standard Deviation 0.93	-1.17 score on a scale Standard Deviation 0.97

PRIMARY outcome

Timeframe: Baseline (Day 0) to Week 12/Final Visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Vaginal pH was obtained at final visit of the study. The pH was a numeric value from a scale of 0 to 14 expressing the acidity or alkalinity of the vaginal fluids where 7 was neutral, lower values were more acidic (values of 0-6) and higher values more alkaline (values of 8-14). A negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Vaginal pH to Week 12/Final Visit Baseline	6.51 score on a scale Standard Deviation 0.96	6.49 score on a scale Standard Deviation 0.86	6.40 score on a scale Standard Deviation 0.93	6.40 score on a scale Standard Deviation 0.86
Change From Baseline in Vaginal pH to Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-1.08 score on a scale Standard Deviation 1.14	-0.37 score on a scale Standard Deviation 0.92	-0.99 score on a scale Standard Deviation 1.05	-0.46 score on a scale Standard Deviation 0.90

PRIMARY outcome

Timeframe: Baseline (Day 0) to Week 12/Final Visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of superficial cells. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=227 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=225 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=117 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Percentage of Vaginal Superficial Cells to Week 12/Final Visit Change from Baseline to Week 12/Final Visit	11.44 percentage of superficial cells Standard Deviation 14.74	3.05 percentage of superficial cells Standard Deviation 7.11	17.30 percentage of superficial cells Standard Deviation 19.27	4.02 percentage of superficial cells Standard Deviation 12.16
Change From Baseline in Percentage of Vaginal Superficial Cells to Week 12/Final Visit Baseline	0.85 percentage of superficial cells Standard Deviation 3.76	0.66 percentage of superficial cells Standard Deviation 1.62	0.79 percentage of superficial cells Standard Deviation 1.63	0.66 percentage of superficial cells Standard Deviation 1.21

PRIMARY outcome

Timeframe: Baseline (Day 0) to Week 12/Final Visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of parabasal cells. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=227 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=225 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=117 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Percentage of Vaginal Parabasal Cells to Week 12/Final Visit Baseline	48.36 percentage of parabasal cells Standard Deviation 43.46	47.78 percentage of parabasal cells Standard Deviation 44.51	42.56 percentage of parabasal cells Standard Deviation 41.03	45.24 percentage of parabasal cells Standard Deviation 42.47
Change From Baseline in Percentage of Vaginal Parabasal Cells to Week 12/Final Visit Change from Baseline to Week 12/Final Visit	41.7 percentage of parabasal cells Standard Deviation 42.76	-8.20 percentage of parabasal cells Standard Deviation 29.56	-38.5 percentage of parabasal cells Standard Deviation 39.78	-16.0 percentage of parabasal cells Standard Deviation 32.75

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 12 and Week 12/Final visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to atrophy scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=233 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Investigator's Assessment of Atrophy to Week 12 and Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-0.74 score on a scale Standard Deviation 0.80	-0.48 score on a scale Standard Deviation 0.72	-0.75 score on a scale Standard Deviation 0.81	-0.44 score on a scale Standard Deviation 0.77
Change From Baseline in Investigator's Assessment of Atrophy to Week 12 and Week 12/Final Visit Baseline	1.88 score on a scale Standard Deviation 0.60	1.94 score on a scale Standard Deviation 0.70	1.90 score on a scale Standard Deviation 0.64	1.88 score on a scale Standard Deviation 0.63
Change From Baseline in Investigator's Assessment of Atrophy to Week 12 and Week 12/Final Visit Change from Baseline to Week 12	-0.77 score on a scale Standard Deviation 0.80	-0.47 score on a scale Standard Deviation 0.71	-0.76 score on a scale Standard Deviation 0.81	-0.44 score on a scale Standard Deviation 0.76

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 12 and Week 12/Final visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to pallor scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Investigator's Assessment of Pallor to Week 12 and Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-0.71 score on a scale Standard Deviation 0.82	-0.39 score on a scale Standard Deviation 0.76	-0.77 score on a scale Standard Deviation 0.80	-0.59 score on a scale Standard Deviation 0.81
Change From Baseline in Investigator's Assessment of Pallor to Week 12 and Week 12/Final Visit Baseline	1.76 score on a scale Standard Deviation 0.67	1.72 score on a scale Standard Deviation 0.76	1.74 score on a scale Standard Deviation 0.70	1.83 score on a scale Standard Deviation 0.67
Change From Baseline in Investigator's Assessment of Pallor to Week 12 and Week 12/Final Visit Change from Baseline to Week 12	-0.73 score on a scale Standard Deviation 0.81	-0.36 score on a scale Standard Deviation 0.75	-0.78 score on a scale Standard Deviation 0.79	-0.59 score on a scale Standard Deviation 0.81

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 12 and Week 12/Final visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to vaginal dryness scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Investigator's Assessment of Vaginal Dryness to Week 12 and Week 12/Final Visit Baseline	1.92 score on a scale Standard Deviation 0.68	1.85 score on a scale Standard Deviation 0.73	1.83 score on a scale Standard Deviation 0.75	1.87 score on a scale Standard Deviation 0.76
Change From Baseline in Investigator's Assessment of Vaginal Dryness to Week 12 and Week 12/Final Visit Change from Baseline to Week 12	-0.94 score on a scale Standard Deviation 0.88	-0.53 score on a scale Standard Deviation 0.82	-0.90 score on a scale Standard Deviation 0.89	-0.74 score on a scale Standard Deviation 0.91
Change From Baseline in Investigator's Assessment of Vaginal Dryness to Week 12 and Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-0.91 score on a scale Standard Deviation 0.89	-0.55 score on a scale Standard Deviation 0.83	-0.89 score on a scale Standard Deviation 0.90	-0.76 score on a scale Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 12 and Week 12/Final visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to friability scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Investigator's Assessment of Friability to Week 12 and Week 12/Final Visit Baseline	1.04 score on a scale Standard Deviation 0.91	1.02 score on a scale Standard Deviation 0.94	0.94 score on a scale Standard Deviation 0.89	1.04 score on a scale Standard Deviation 0.93
Change From Baseline in Investigator's Assessment of Friability to Week 12 and Week 12/Final Visit Change from Baseline to Week 12	-0.66 score on a scale Standard Deviation 0.90	-0.47 score on a scale Standard Deviation 0.86	-0.60 score on a scale Standard Deviation 0.87	-0.52 score on a scale Standard Deviation 0.89
Change From Baseline in Investigator's Assessment of Friability to Week 12 and Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-0.64 score on a scale Standard Deviation 0.89	-0.48 score on a scale Standard Deviation 0.86	-0.61 score on a scale Standard Deviation 0.86	-0.52 score on a scale Standard Deviation 0.89

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 12 and Week 12/Final visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to petechiae scored on a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Investigator's Assessment of Petechiae to Week 12 and Week 12/Final Visit Change from Baseline to Week 12	-0.47 score on a scale Standard Deviation 0.74	-0.38 score on a scale Standard Deviation 0.72	-0.47 score on a scale Standard Deviation 0.82	-0.29 score on a scale Standard Deviation 0.73
Change From Baseline in Investigator's Assessment of Petechiae to Week 12 and Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-0.44 score on a scale Standard Deviation 0.73	-0.40 score on a scale Standard Deviation 0.71	-0.46 score on a scale Standard Deviation 0.82	-0.30 score on a scale Standard Deviation 0.75
Change From Baseline in Investigator's Assessment of Petechiae to Week 12 and Week 12/Final Visit Baseline	0.74 score on a scale Standard Deviation 0.78	0.89 score on a scale Standard Deviation 0.89	0.70 score on a scale Standard Deviation 0.83	0.71 score on a scale Standard Deviation 0.81

SECONDARY outcome

Timeframe: Baseline (Day 0) to Weeks 2, 4, 8 and 12

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Participant's self-assessment of symptoms of VVA (severity of vaginal dryness) was scored according to a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8 and 12 Baseline	2.49 score on a scale Standard Deviation 0.50	2.46 score on a scale Standard Deviation 0.52	2.50 score on a scale Standard Deviation 0.50	2.50 score on a scale Standard Deviation 0.50
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	-0.83 score on a scale Standard Deviation 0.86	-0.79 score on a scale Standard Deviation 0.88	-0.95 score on a scale Standard Deviation 0.90	-0.79 score on a scale Standard Deviation 0.84
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	-1.07 score on a scale Standard Deviation 0.82	-0.93 score on a scale Standard Deviation 0.90	-1.12 score on a scale Standard Deviation 0.91	-0.95 score on a scale Standard Deviation 0.90
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	-1.25 score on a scale Standard Deviation 0.84	-1.02 score on a scale Standard Deviation 0.90	-1.43 score on a scale Standard Deviation 0.90	-1.11 score on a scale Standard Deviation 0.91
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	-1.30 score on a scale Standard Deviation 0.91	-0.97 score on a scale Standard Deviation 0.90	-1.36 score on a scale Standard Deviation 0.94	-1.20 score on a scale Standard Deviation 0.98

SECONDARY outcome

Timeframe: Baseline (Day 0) to Weeks 2, 4, 8, 12 and Week 12/Final visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Participant's self-assessment of symptoms of VVA (vaginal and/or vulvar irritation/itching) was scored according to a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Participant's Self-Assessment of Vaginal and/or Vulvar Irritation/Itching to Weeks 2, 4, 8, 12 and Week 12/Final Visit Baseline	1.26 score on a scale Standard Deviation 0.96	1.33 score on a scale Standard Deviation 1.00	1.11 score on a scale Standard Deviation 0.96	1.20 score on a scale Standard Deviation 0.89
Change From Baseline in Participant's Self-Assessment of Vaginal and/or Vulvar Irritation/Itching to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 2	-0.54 score on a scale Standard Deviation 1.09	-0.67 score on a scale Standard Deviation 0.95	-0.48 score on a scale Standard Deviation 1.05	-0.48 score on a scale Standard Deviation 1.04
Change From Baseline in Participant's Self-Assessment of Vaginal and/or Vulvar Irritation/Itching to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 4	-0.62 score on a scale Standard Deviation 1.14	-0.71 score on a scale Standard Deviation 0.92	-0.48 score on a scale Standard Deviation 1.08	-0.65 score on a scale Standard Deviation 1.01
Change From Baseline in Participant's Self-Assessment of Vaginal and/or Vulvar Irritation/Itching to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 8	-0.71 score on a scale Standard Deviation 1.11	-0.82 score on a scale Standard Deviation 1.03	-0.57 score on a scale Standard Deviation 0.97	-0.58 score on a scale Standard Deviation 1.00
Change From Baseline in Participant's Self-Assessment of Vaginal and/or Vulvar Irritation/Itching to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 12	-0.75 score on a scale Standard Deviation 1.03	-0.74 score on a scale Standard Deviation 1.02	-0.59 score on a scale Standard Deviation 1.04	-0.70 score on a scale Standard Deviation 0.86
Change From Baseline in Participant's Self-Assessment of Vaginal and/or Vulvar Irritation/Itching to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-0.74 score on a scale Standard Deviation 1.01	-0.74 score on a scale Standard Deviation 1.03	-0.58 score on a scale Standard Deviation 1.02	-0.63 score on a scale Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline (Day 0) to Weeks 2, 4, 8, 12 and Week 12/Final visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Participant's self-assessment of symptoms of VVA (dysuria) was scored according to a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Participant's Self-Assessment of Dysuria (Painful or Difficult Urination) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Baseline	0.38 score on a scale Standard Deviation 0.70	0.49 score on a scale Standard Deviation 0.75	0.45 score on a scale Standard Deviation 0.75	0.53 score on a scale Standard Deviation 0.80
Change From Baseline in Participant's Self-Assessment of Dysuria (Painful or Difficult Urination) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 2	-0.24 score on a scale Standard Deviation 0.67	-0.22 score on a scale Standard Deviation 0.71	-0.28 score on a scale Standard Deviation 0.74	-0.38 score on a scale Standard Deviation 0.77
Change From Baseline in Participant's Self-Assessment of Dysuria (Painful or Difficult Urination) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 4	-0.20 score on a scale Standard Deviation 0.68	-0.30 score on a scale Standard Deviation 0.60	-0.28 score on a scale Standard Deviation 0.76	-0.42 score on a scale Standard Deviation 0.77
Change From Baseline in Participant's Self-Assessment of Dysuria (Painful or Difficult Urination) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 8	-0.20 score on a scale Standard Deviation 0.75	-0.28 score on a scale Standard Deviation 0.72	-0.32 score on a scale Standard Deviation 0.75	-0.34 score on a scale Standard Deviation 0.85
Change From Baseline in Participant's Self-Assessment of Dysuria (Painful or Difficult Urination) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 12	-0.28 score on a scale Standard Deviation 0.68	-0.28 score on a scale Standard Deviation 0.64	-0.36 score on a scale Standard Deviation 0.72	-0.41 score on a scale Standard Deviation 0.79
Change From Baseline in Participant's Self-Assessment of Dysuria (Painful or Difficult Urination) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-0.27 score on a scale Standard Deviation 0.66	-0.27 score on a scale Standard Deviation 0.64	-0.34 score on a scale Standard Deviation 0.75	-0.39 score on a scale Standard Deviation 0.78

SECONDARY outcome

Timeframe: Baseline (Day 0) to Weeks 2, 4, 8, 12 and Week 12/Final visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Participant's self-assessment of symptoms of VVA (dyspareunia) was scored according to a 4-point scale where: 0= none, 1= mild, 2= moderate, or 3= severe. The negative change from Baseline indicates improvement. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=203 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=116 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=208 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=109 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Participant's Self-Assessment of Dyspareunia (Pain Associated With Sexual Activity) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Baseline	2.29 score on a scale Standard Deviation 0.93	2.23 score on a scale Standard Deviation 0.88	2.29 score on a scale Standard Deviation 0.85	2.38 score on a scale Standard Deviation 0.86
Change From Baseline in Participant's Self-Assessment of Dyspareunia (Pain Associated With Sexual Activity) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 2	-0.79 score on a scale Standard Deviation 1.06	-0.78 score on a scale Standard Deviation 1.07	-0.86 score on a scale Standard Deviation 1.06	-0.67 score on a scale Standard Deviation 1.01
Change From Baseline in Participant's Self-Assessment of Dyspareunia (Pain Associated With Sexual Activity) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 4	-1.04 score on a scale Standard Deviation 1.06	-1.03 score on a scale Standard Deviation 0.90	-1.06 score on a scale Standard Deviation 1.03	-0.78 score on a scale Standard Deviation 0.91
Change From Baseline in Participant's Self-Assessment of Dyspareunia (Pain Associated With Sexual Activity) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 12/Final Visit	-1.15 score on a scale Standard Deviation 1.07	-1.03 score on a scale Standard Deviation 1.00	-1.35 score on a scale Standard Deviation 1.02	-1.06 score on a scale Standard Deviation 1.07
Change From Baseline in Participant's Self-Assessment of Dyspareunia (Pain Associated With Sexual Activity) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 8	-1.08 score on a scale Standard Deviation 1.01	-1.04 score on a scale Standard Deviation 0.96	-1.36 score on a scale Standard Deviation 0.97	-1.07 score on a scale Standard Deviation 1.09
Change From Baseline in Participant's Self-Assessment of Dyspareunia (Pain Associated With Sexual Activity) to Weeks 2, 4, 8, 12 and Week 12/Final Visit Change from Baseline to Week 12	-1.15 score on a scale Standard Deviation 1.09	-1.06 score on a scale Standard Deviation 0.96	-1.39 score on a scale Standard Deviation 1.01	-1.09 score on a scale Standard Deviation 1.05

SECONDARY outcome

Timeframe: Baseline (Day 0) and Weeks 2, 4, 8, 12 and Week 12/Final visit

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Vaginal bleeding associated with sexual activity was assessed by participants as either "present" or "absent". Percentage of participants with assessment "present" are reported. Week 12/Final Visit is defined as the last available postbaseline assessment up to Week 12.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity as Per Participant's Self-Assessment to Weeks 2, 4, 8, 12 and Week 12/Final Visit Baseline	15.81 percentage of participants	17.89 percentage of participants	17.75 percentage of participants	24.79 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity as Per Participant's Self-Assessment to Weeks 2, 4, 8, 12 and Week 12/Final Visit Week 2	6.55 percentage of participants	7.32 percentage of participants	6.11 percentage of participants	9.24 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity as Per Participant's Self-Assessment to Weeks 2, 4, 8, 12 and Week 12/Final Visit Week 4	5.29 percentage of participants	6.50 percentage of participants	2.64 percentage of participants	5.00 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity as Per Participant's Self-Assessment to Weeks 2, 4, 8, 12 and Week 12/Final Visit Week 8	4.61 percentage of participants	4.96 percentage of participants	2.74 percentage of participants	6.90 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity as Per Participant's Self-Assessment to Weeks 2, 4, 8, 12 and Week 12/Final Visit Week 12	6.94 percentage of participants	5.04 percentage of participants	3.35 percentage of participants	6.19 percentage of participants
Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity as Per Participant's Self-Assessment to Weeks 2, 4, 8, 12 and Week 12/Final Visit Week 12/Final Visit	6.44 percentage of participants	4.88 percentage of participants	3.03 percentage of participants	5.79 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 12

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

Vaginal pH was obtained at final visit of the study. The pH was a numeric value from a scale of 0 to 14 expressing the acidity or alkalinity of the vaginal fluids where 7 was neutral, lower values were more acidic (values of 0-6) and higher values more alkaline (values of 8-14). A negative change from Baseline indicates improvement.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=234 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=231 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=121 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Vaginal pH to Week 12 Change from Baseline to Week 12	-1.10 score on a scale Standard Deviation 1.15	-0.34 score on a scale Standard Deviation 0.89	-1.01 score on a scale Standard Deviation 1.06	-0.47 score on a scale Standard Deviation 0.87
Change From Baseline in Vaginal pH to Week 12 Baseline	6.51 score on a scale Standard Deviation 0.96	6.49 score on a scale Standard Deviation 0.86	6.40 score on a scale Standard Deviation 0.93	6.40 score on a scale Standard Deviation 0.86

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 12

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

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.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=227 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=225 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=117 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Percentage of Vaginal Superficial Cells to Week 12 Baseline	0.85 percentage of superficial cells Standard Deviation 3.76	0.66 percentage of superficial cells Standard Deviation 1.62	0.79 percentage of superficial cells Standard Deviation 1.63	0.66 percentage of superficial cells Standard Deviation 1.21
Change From Baseline in Percentage of Vaginal Superficial Cells to Week 12 Change from Baseline to Week 12	11.66 percentage of superficial cells Standard Deviation 14.51	3.17 percentage of superficial cells Standard Deviation 7.02	17.66 percentage of superficial cells Standard Deviation 19.37	3.36 percentage of superficial cells Standard Deviation 10.31

SECONDARY outcome

Timeframe: Baseline (Day 0) to Week 12

Population: mITT Population included all participants in the safety population who had at least one postbaseline primary efficacy result. Number analyzed is the number of participants with evaluable data at the given timepoint.

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.

Outcome measures

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=227 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=123 Participants Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=225 Participants WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=117 Participants Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Change From Baseline in Percentage of Vaginal Parabasal Cells to Week 12 Change from Baseline to Week 12	-42.3 percentage of parabasal cells Standard Deviation 42.90	-8.08 percentage of parabasal cells Standard Deviation 29.90	-39.5 percentage of parabasal cells Standard Deviation 39.46	-14.9 percentage of parabasal cells Standard Deviation 31.93
Change From Baseline in Percentage of Vaginal Parabasal Cells to Week 12 Baseline	48.36 percentage of parabasal cells Standard Deviation 43.46	47.78 percentage of parabasal cells Standard Deviation 44.51	42.56 percentage of parabasal cells Standard Deviation 41.03	45.24 percentage of parabasal cells Standard Deviation 42.47

Adverse Events

WC3011 Estradiol Vaginal Cream (2 Times/Week)

Serious events: 1 serious events

Other events: 46 other events

Deaths: 0 deaths

Vehicle (2 Times/Week)

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

WC3011 Estradiol Vaginal Cream (3 Times/Week)

Serious events: 0 serious events

Other events: 57 other events

Deaths: 0 deaths

Vehicle (3 Times/Week)

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=238 participants at risk WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=124 participants at risk Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=237 participants at risk WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=123 participants at risk Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Hepatobiliary disorders Cholecystitis	0.00% 0/238 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	0.00% 0/124 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	0.00% 0/237 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	0.81% 1/123 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Large intestine perforation	0.42% 1/238 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	0.00% 0/124 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	0.00% 0/237 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	0.00% 0/123 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.42% 1/238 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	0.00% 0/124 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	0.00% 0/237 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	0.00% 0/123 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.

Other adverse events

Measure	WC3011 Estradiol Vaginal Cream (2 Times/Week) n=238 participants at risk WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	Vehicle (2 Times/Week) n=124 participants at risk Vehicle applied daily for 2 weeks, followed by dosing 2 times a week for 10 weeks.	WC3011 Estradiol Vaginal Cream (3 Times/Week) n=237 participants at risk WC3011 estradiol vaginal cream applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.	Vehicle (3 Times/Week) n=123 participants at risk Vehicle applied daily for 2 weeks, followed by dosing 3 times a week for 10 weeks.
Infections and infestations Vulvovaginal mycotic infection	5.0% 12/238 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	2.4% 3/124 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	11.0% 26/237 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	6.5% 8/123 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.
Reproductive system and breast disorders Vaginal discharge	5.5% 13/238 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	3.2% 4/124 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	4.2% 10/237 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	2.4% 3/123 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	3.4% 8/238 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	4.0% 5/124 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	5.1% 12/237 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	1.6% 2/123 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Urinary tract infection	5.0% 12/238 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	5.6% 7/124 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	3.0% 7/237 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	5.7% 7/123 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.
Infections and infestations Nasopharyngitis	1.3% 3/238 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	1.6% 2/124 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	4.6% 11/237 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.	6.5% 8/123 • From first dose through the last study visit (Up to 12 weeks) The safety population included all participants who were randomized and received at least one dose of study drug.

Additional Information

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: clinicaltrials@allergan.com

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