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

• Sponsor: Warner Chilcott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01816139
• Collaborator: (none)
• Enrollment: 576
• Locations: 48
• Arms: 2
• Actual Duration (Months): 9.6
• Patients Per Site: 12
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The primary objective of this study is to compare the efficacy of WC3011 with placebo vaginal gel in postmenopausal women for the relief of vaginal dryness caused by vaginal atrophy as measured by self-assessment, vaginal pH and vaginal smear.

Condition or Disease	Intervention/Treatment	Phase
Vulvovaginal Atrophy	Drug: Vehicle; Drug: WC3011 Estradiol Vaginal Cream	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 576 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Double-Blind, Vehicle-Controlled Study to Evaluate the Safety and Efficacy of WC3011 in Postmenopausal Women
• Actual Study Start Date: Jan 31, 2013
• Actual Primary Completion Date: Nov 19, 2013
• Actual Study Completion Date: Nov 19, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vehicle (2 Times/Week) Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	Drug: Vehicle; Vehicle Cream applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks
Placebo Comparator: 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.	Drug: WC3011 Estradiol Vaginal Cream; WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Final Assessment [Baseline (Day 0) to final assessment (Up to Week 12)]

   Participant's self-assessment of Vaginal Dryness was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment.

2. Change From Baseline in Vaginal pH to Final Assessment [Baseline (Day 0) to final assessment (Up to Week 12)]

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

3. 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.

4. 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 Outcome Measures

1. Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12 [Baseline (Day 0) to Weeks 2, 4, 8, and 12]

   Participant's self-assessment of Vaginal Dryness was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement.

2. Change From Baseline in Participants Self-Assessment of the Symptoms of VVA [Baseline (Day 0) to Weeks 2, 4, 8, 12 and Final Assessment]

   Self-Assessment of the symptoms of VVA (vaginal and/or vulvar irritation/ Itching, dysuria, and dyspareunia) were evaluated by a questionnaire. Each symptom was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate, or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement. Final Assessment is defined as the last available post-baseline assessment for the given efficacy endpoint.

3. Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity [Baseline (Day 0) and Weeks 2, 4, 8, 12 and Final Assessment]

   Vaginal bleeding associated with sexual activity was assessed by participants as either "present" or "absent". Number of participants with assessment "present" are reported. Final assessment is defined as the last available postbaseline assessment.

4. Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment [Baseline (Day 0) to Week 12 and Final Assessment]

   Investigator's assessment of vaginal health was performed by visual inspection of the vagina with respect to the signs of VVA: atrophy, pallor, vaginal dryness, friability, and petechiae each graded on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores are worse. A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment.

5. Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12 [Baseline (Day 0) to Week 12]

   Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of superficial cells. A positive change from Baseline indicates improvement.

6. Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12 [Baseline (Day 0) to Week 12]

   Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of parabasal cells. A negative change from Baseline indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed informed consent

• Moderate to severe vaginal dryness

• Postmenopausal meeting one of the following: 12 months spontaneous amenorrhea, 6 months spontaneous amenorrhea with serum Follicle-stimulating hormone (FSH) > 40 milli-International Unit (mIU)/mL, 6 weeks postsurgical bilateral oophorectomy confirmed by surgical report, ultrasound or serum FSH > 40 mIU/mL, 6 weeks postsurgical hysterectomy with ovary failure confirmed by serum FSH > 40 mIU/mL

• Age ≥ 40 years or if bilateral oophorectomy ≥ 35 years

• Vaginal pH >5.0

• Less than or equal 5% superficial cells on vaginal wall cytologic smear

• Normal breast exam; if > 40 years, documentation of negative mammogram

Exclusion Criteria:

• Randomization in PR-04409, participation in clinical trial or use of investigational drug within 30 days prior to screening

• Smokes ≥ 15 cigarettes/day

• Known or suspected premalignant or malignant disease

• Cardiovascular disease, insulin-dependent diabetes mellitus, congestive heart failure, stroke or ischemic attack, thrombophlebitis or thromboembolic disorder

• Increased frequency/severity headaches with estrogen therapy

• Drug addiction/alcohol abuse within last 2 years

• Currently taking St. John's Wort or anticoagulant

• Uncontrolled hypertension or thyroid disorder, clinically significant depression or untreated urinary tract infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warner Chilcott Investigational Study Site	Huntsville	Alabama	United States	35801
2	Warner Chilcott Investigational Study Site	Mobile	Alabama	United States	36608
3	Warner Chilcott Investigational Study Site	Phoenix	Arizona	United States	85032
4	Warner Chilcott Investigational Study Site	Scottsdale	Arizona	United States	85251
5	Warner Chilcott Investigational Study Site	Tucson	Arizona	United States	85712
6	Warner Chilcott Investigational Study Site	San Diego	California	United States	92103
7	Warner Chilcott Investigational Study Site	San Diego	California	United States	92108
8	Warner Chilcott Investigational Study Site	San Diego	California	United States	92123
9	Warner Chilcott Investigational Study Site	New London	Connecticut	United States	06320
10	Warner Chilcott Investigational Study Site	Boynton Beach	Florida	United States	33472
11	Warner Chilcott Investigational Study Site	Clearwater	Florida	United States	33759
12	Warner Chilcott Investigational Study Site	Jacksonville	Florida	United States	32216
13	Warner Chilcott Investigational Study Site	Miami	Florida	United States	33143
14	Warner Chilcott Investigational Study Site	Miami	Florida	United States	33186
15	Warner Chilcott Investigational Study Site	Ormond Beach	Florida	United States	32174
16	Warner Chilcott Investigational Study Site	Palm Beach Gardens	Florida	United States	33410
17	Warner Chilcott Investigational Study Site	Pinellas Park	Florida	United States	33781
18	Warner Chilcott Investigational Study Site	West Palm Beach	Florida	United States	33409
19	Warner Chilcott Investigational Study Site	Atlanta	Georgia	United States	30328
20	Warner Chilcott Investigational Study Site	Roswell	Georgia	United States	30075
21	Warner Chilcott Investigational Study Site	Savannah	Georgia	United States	31406
22	Warner Chilcott Investigational Study Site	Granger	Indiana	United States	46530
23	Warner Chilcott Investigational Study Site	Marrero	Louisiana	United States	70072
24	Warner Chilcott Investigational Study Site	New Orleans	Louisiana	United States	70115
25	Warner Chilcott Investigational Study Site	Kalamazoo	Michigan	United States	49009
26	Warner Chilcott Investigational Study Site	Las Vegas	Nevada	United States	89106
27	Warner Chilcott Investigational Study Site	Las Vegas	Nevada	United States	89113
28	Warner Chilcott Investigational Study Site	Moorestown	New Jersey	United States	08057
29	Warner Chilcott Investigational Study Site	Greensboro	North Carolina	United States	27408
30	Warner Chilcott Investigational Study Site	New Bern	North Carolina	United States	28562
31	Warner Chilcott Investigational Study Site	Winston-Salem	North Carolina	United States	27103
32	Warner Chilcott Investigational Study Site	Cleveland	Ohio	United States	44122
33	Warner Chilcott Investigational Study Site	Columbus	Ohio	United States	43213
34	Warner Chilcott Investigational Study Site	Jenkintown	Pennsylvania	United States	19046
35	Warner Chilcott Investigational Study Site	Philadelphia	Pennsylvania	United States	19114
36	Warner Chilcott Investigational Study Site	Pittsburgh	Pennsylvania	United States	15206
37	Warner Chilcott Investigational Study Site	Bluffton	South Carolina	United States	29910
38	Warner Chilcott Investigational Study Site	Dallas	Texas	United States	75230
39	Warner Chilcott Investigational Study Site	Dallas	Texas	United States	75231
40	Warner Chilcott Investigational Study Site	Dallas	Texas	United States	75234
41	Warner Chilcott Investigational Study Site	Houston	Texas	United States	77030
42	Warner Chilcott Investigational Study Site	San Antonio	Texas	United States	78229
43	Warner Chilcott Investigational Study Site	Salt Lake City	Utah	United States	84109
44	Warner Chilcott Investigational Study Site	Salt Lake City	Utah	United States	84121
45	Warner Chilcott Investigational Study Site	Norfolk	Virginia	United States	23507
46	Warner Chilcott Investigational Study Site	Richmond	Virginia	United States	23233
47	Warner Chilcott Investigational Study Site	Seattle	Washington	United States	98105
48	Warner Chilcott Investigational Study Site	Spokane	Washington	United States	99207

Sponsors and Collaborators

• Warner Chilcott

Investigators

• Study Director: Anna Chan, PharmD, Warner Chilcott

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Warner Chilcott
• ClinicalTrials.gov Identifier: NCT01816139
• Other Study ID Numbers: PR-05812
• First Posted: Mar 21, 2013
• Last Update Posted: May 9, 2022
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Warner Chilcott: vaginal dryness; vaginal atrophy; estrogen
• Additional relevant MeSH terms: Atrophy; Estradiol

Study Results

Participant Flow

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Period Title: Overall Study
STARTED	289	287
Safety Population	287	286
Modified Intent-to-treat (mITT) Population	240	248
COMPLETED	261	265
NOT COMPLETED	28	22

Baseline Characteristics

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)	Total
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	Total of all reporting groups
Overall Participants	287	286	573
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.8 (6.1)	59.5 (6.7)	59.6 (6.4)
Sex: Female, Male (Count of Participants)
Female	287 100%	286 100%	573 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Final Assessment
Description	Participant's self-assessment of Vaginal Dryness was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment.
Time Frame	Baseline (Day 0) to final assessment (Up to Week 12)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat (mITT) Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	240	248
Baseline	2.5 (0.50)	2.5 (0.50)
Change from Baseline to Final Assessment	-1.2 (0.92)	-1.4 (0.94)

2. Primary Outcome

Title	Change From Baseline in Vaginal pH to Final Assessment
Description	Vaginal pH was obtained at baseline and final visit of the study. The pH was a numeric value from 0 to 14 expressing the acidity or alkalinity of the vaginal fluids where 7 was neutral, lower values were more acidic (values of 0-6) and higher values more alkaline (values of 8-14). A negative change from Baseline indicates improvement. Final assessment is defined as the last available postbaseline assessment.
Time Frame	Baseline (Day 0) to final assessment (Up to Week 12)

Outcome Measure Data

Analysis Population Description

mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	240	248
Baseline	6.33 (0.65)	6.34 (0.65)
Change from Baseline to Final Assessment	-0.31 (0.80)	-1.26 (0.99)

3. Primary Outcome

Title	Change From Baseline in the Percentage of Vaginal Superficial Cells to Final Assessment
Description	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)

Outcome Measure Data

Analysis Population Description

mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	240	248
Baseline	0.3 (1.05)	0.4 (1.13)
Change from Baseline to Final Assessment	0.8 (5.68)	8.6 (14.49)

4. Primary Outcome

Title	Change From Baseline in the Percentage of Vaginal Parabasal Cells to Final Assessment
Description	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)

Outcome Measure Data

Analysis Population Description

mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	240	248
Baseline	46.5 (44.81)	44.2 (42.29)
Change from Baseline to Final Assessment	-4.4 (42.93)	-37.4 (42.62)

5. Secondary Outcome

Title	Change From Baseline in Participant's Self-Assessment of Severity of Vaginal Dryness to Weeks 2, 4, 8, and 12
Description	Participant's self-assessment of Vaginal Dryness was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 0) to Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	240	248
Baseline	2.5 (0.50)	2.5 (0.50)
Change from Baseline to Week 2	-0.9 (0.92)	-1.0 (0.94)
Change from Baseline to Week 4	-1.1 (0.87)	-1.2 (0.86)
Change from Baseline to Week 8	-1.2 (0.87)	-1.4 (0.85)
Change from Baseline to Week 12	-1.2 (0.90)	-1.5 (0.93)

6. Secondary Outcome

Title	Change From Baseline in Participants Self-Assessment of the Symptoms of VVA
Description	Self-Assessment of the symptoms of VVA (vaginal and/or vulvar irritation/ Itching, dysuria, and dyspareunia) were evaluated by a questionnaire. Each symptom was scored on a 4-point scale where: 0=none, 1=mild, 2=moderate, or 3=severe. Higher scores indicate the most bothersome symptoms. A negative change from Baseline indicates improvement. Final Assessment is defined as the last available post-baseline assessment for the given efficacy endpoint.
Time Frame	Baseline (Day 0) to Weeks 2, 4, 8, 12 and Final Assessment

Outcome Measure Data

Analysis Population Description

mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	240	248
Vaginal Itching - Baseline	1.1 (0.97)	1.1 (0.97)
Vaginal Itching - Change from Baseline to Week 2	-0.5 (0.93)	-0.5 (0.95)
Vaginal Itching - Change from Baseline to Week 4	-0.6 (0.99)	-0.6 (0.89)
Vaginal Itching - Change from Baseline to Week 8	-0.6 (0.95)	-0.6 (0.92)
Vaginal Itching - Change from Baseline to Week 12	-0.7 (1.00)	-0.7 (0.94)
Vaginal Itching - Change from Baseline to Final Assessment	-0.7 (0.99)	-0.6 (0.99)
Dysuria - Baseline	0.3 (0.66)	0.4 (0.72)
Dysuria - Change from Baseline to Week 2	-0.1 (0.71)	-0.2 (0.66)
Dysuria - Change from Baseline to Week 4	-0.1 (0.75)	-0.2 (0.69)
Dysuria - Change from Baseline to Week 8	-0.2 (0.65)	-0.2 (0.75)
Dysuria - Change from Baseline to Week 12	-0.2 (0.65)	-0.2 (0.69)
Dysuria - Change from Baseline to Final Assessment	-0.2 (0.64)	-0.2 (0.71)
Dyspareunia - Baseline	2.1 (0.92)	2.1 (0.99)
Dyspareunia - Change from Baseline to Week 2	-0.7 (0.91)	-0.7 (1.04)
Dyspareunia - Change from Baseline to Week 4	-1.0 (0.90)	-1.1 (1.05)
Dyspareunia - Change from Baseline to Week 8	-0.9 (0.99)	-1.2 (1.03)
Dyspareunia - Change from Baseline to Week 12	-1.1 (0.97)	-1.1 (1.12)
Dyspareunia - Change from Baseline to Final Assessment	-1.0 (0.95)	-1.1 (1.11)

7. Secondary Outcome

Title	Percentage of Participants With Vaginal Bleeding Associated With Sexual Activity
Description	Vaginal bleeding associated with sexual activity was assessed by participants as either "present" or "absent". Number of participants with assessment "present" are reported. Final assessment is defined as the last available postbaseline assessment.
Time Frame	Baseline (Day 0) and Weeks 2, 4, 8, 12 and Final Assessment

Outcome Measure Data

Analysis Population Description

mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	184	177
Baseline	18.5 6.4%	24.3 8.5%
Week 2	8.4 2.9%	8.4 2.9%
Week 4	6.1 2.1%	4.6 1.6%
Week 8	8.0 2.8%	6.7 2.3%
Week 12	6.6 2.3%	3.8 1.3%
Final Assessment	7.9 2.8%	5.1 1.8%

8. Secondary Outcome

Title	Change From Baseline in the Investigator's Assessment of Each of the Signs of VVA to Week 12 and Final Assessment
Description	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

Outcome Measure Data

Analysis Population Description

mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	240	248
Atrophy - Baseline	2.1 (0.60)	2.0 (0.65)
Atrophy - Change from Baseline to Week 12	-0.4 (0.74)	-0.7 (0.80)
Atrophy - Change from Baseline to Final Assessment	-0.4 (0.74)	-0.7 (0.79)
Pallor - Baseline	1.9 (0.67)	1.9 (0.66)
Pallor - Change from Baseline to Week 12	-0.4 (0.79)	-0.9 (0.79)
Pallor - Change from Baseline to Final Assessment	-0.4 (0.79)	-0.9 (0.82)
Dryness - Baseline	2.0 (0.65)	2.0 (0.69)
Dryness - Change from Baseline to Week 12	-0.6 (0.84)	-1.1 (0.89)
Dryness - Change from Baseline to Final Assessment	-0.6 (0.84)	-1.1 (0.89)
Friability - Baseline	1.1 (0.86)	1.1 (0.86)
Friability - Change from Baseline to Week 12	-0.5 (0.81)	-0.8 (0.92)
Friability - Change from Baseline to Final Assessment	-0.5 (0.81)	-0.8 (0.92)
Petechiae - Baseline	0.8 (0.86)	0.8 (0.82)
Petechiae - Change from Baseline to Week 12	-0.4 (0.71)	-0.6 (0.82)
Petechiae - Change from Baseline to Final Assessment	-0.4 (0.74)	-0.6 (0.83)

9. Secondary Outcome

Title	Change From Baseline in the Percentage of Vaginal Superficial Cells to Week 12
Description	Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of superficial cells. A positive change from Baseline indicates improvement.
Time Frame	Baseline (Day 0) to Week 12

Outcome Measure Data

Analysis Population Description

mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	240	248
Baseline	0.3 (1.05)	0.4 (1.13)
Change from Baseline to Week 12	0.6 (3.35)	9.3 (14.87)

10. Secondary Outcome

Title	Change From Baseline in the Percentage of Vaginal Parabasal Cells to Week 12
Description	Vaginal wall smears were collected from each participant. The smears were sent to the central laboratory for analysis to determine the percentage of parabasal cells. A negative change from Baseline indicates improvement.
Time Frame	Baseline (Day 0) to Week 12

Outcome Measure Data

Analysis Population Description

mITT Population included participants in safety population who had at least 1 postbaseline primary efficacy assessment and had: ≤5% superficial cells on a vaginal wall smear, a vaginal pH >5.0 and participant's most bothersome symptom of VVA was vaginal dryness with moderate to severe intensity. Number analyzed is the number of participants with available data at the given timepoint.

Arm/Group Title	Vehicle (2 Times/Week)	WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.	WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
Measure Participants	240	248
Baseline	46.5 (44.81)	44.2 (42.29)
Change from Baseline to Week 12	-4.7 (43.39)	-38.7 (41.58)

Adverse Events

Time Frame	From first dose through the last study visit (Up to 12 weeks)
Adverse Event Reporting Description	Safety Population included all participants who were randomized into the study and took at least 1 dose of study drug.
Arm/Group Title	Vehicle (2 Times/Week)		WC3011 Estradiol Vaginal Cream (2 Times/Week)
Arm/Group Description	Vehicle applied to the vagina daily for 2 weeks followed by dosing 2 times a week for 10 weeks.		WC3011 estradiol vaginal cream applied daily for 2 weeks followed by dosing 2 times a week for 10 weeks.
All Cause Mortality
	Vehicle (2 Times/Week)		WC3011 Estradiol Vaginal Cream (2 Times/Week)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/287 (0%)		0/286 (0%)
Serious Adverse Events
	Vehicle (2 Times/Week)		WC3011 Estradiol Vaginal Cream (2 Times/Week)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/287 (0.7%)		2/286 (0.7%)
Cardiac disorders
Myocardial Infarction	0/287 (0%)		1/286 (0.3%)
Gastrointestinal disorders
Hiatus Hernia	0/287 (0%)		1/286 (0.3%)
General disorders
Non-Cardiac Chest Pain	1/287 (0.3%)		0/286 (0%)
Infections and infestations
Postoperative Wound Infection	1/287 (0.3%)		0/286 (0%)
Other (Not Including Serious) Adverse Events
	Vehicle (2 Times/Week)		WC3011 Estradiol Vaginal Cream (2 Times/Week)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/287 (12.2%)		38/286 (13.3%)
General disorders
Application site pain	16/287 (5.6%)		9/286 (3.1%)
Infections and infestations
Urinary tract infection	17/287 (5.9%)		15/286 (5.2%)
Vulvovaginal mycotic infection	3/287 (1%)		15/286 (5.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.