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Estradiol Vaginal Softgel Capsules in Treating Symptoms of Vulvar and Vaginal Atrophy in Postmenopausal Women (REJOICE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02253173
Recruitment Status : Completed
First Posted : October 1, 2014
Results First Posted : May 25, 2017
Last Update Posted : May 25, 2017
Sponsor:
Information provided by (Responsible Party):
TherapeuticsMD

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Vulvovaginal Atrophy
Menopause
Dyspareunia
Painful Intercourse
Interventions Drug: Estradiol
Drug: Placebo
Enrollment 764
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Period Title: Overall Study
Started 191 191 190 192
Completed 175 174 177 178
Not Completed 16 17 13 14
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule Total
Hide Arm/Group Description

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Total of all reporting groups
Overall Number of Baseline Participants 191 191 190 192 764
Hide Baseline Analysis Population Description
The modified intent to treat (MITT) population was the primary efficacy population, defined as all ITT subjects who received the treatment to which they were randomized, had baseline values for all co-primary variables, and had at least one post-baseline value for any of the four co-primary variables at any visit.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 191 participants 191 participants 190 participants 192 participants 764 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
148
  77.5%
162
  84.8%
156
  82.1%
151
  78.6%
617
  80.8%
>=65 years
43
  22.5%
29
  15.2%
34
  17.9%
41
  21.4%
147
  19.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 191 participants 191 participants 190 participants 192 participants 764 participants
59.8  (5.90) 58.5  (6.29) 58.9  (6.26) 59.3  (6.07) 59.1  (6.14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 191 participants 191 participants 190 participants 192 participants 764 participants
Female
191
 100.0%
191
 100.0%
190
 100.0%
192
 100.0%
764
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 191 participants 191 participants 190 participants 192 participants 764 participants
Canada 13 10 15 12 50
United States 178 181 175 180 714
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters
Number Analyzed 191 participants 191 participants 190 participants 192 participants 764 participants
162.7  (6.86) 162.9  (6.93) 162.3  (6.37) 162.2  (6.30) 162.5  (6.62)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 191 participants 191 participants 190 participants 192 participants 764 participants
70.4  (14.26) 71.1  (13.49) 70.6  (13.7) 70.4  (13.6) 70.6  (13.74)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 191 participants 191 participants 190 participants 192 participants 764 participants
26.5  (4.87) 26.8  (4.68) 26.7  (4.79) 26.7  (4.59) 26.7  (4.73)
1.Primary Outcome
Title Co-Primary Efficacy Endpoint - Vaginal Superficial Cells
Hide Description • Change from Baseline to Week 12 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
Time Frame Baseline and 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo
Hide Arm/Group Description:
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Overall Number of Participants Analyzed 170 171 174 172
Least Squares Mean (Standard Error)
Unit of Measure: percentage of vaginal superficial cells
17.50  (1.542) 16.72  (1.540) 23.20  (1.529) 5.63  (1.537)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
2.Primary Outcome
Title Co-Primary Efficacy Endpoint - Vaginal Parabasal Cells
Hide Description • Change from Baseline to Week 12 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
Time Frame Baseline and 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo
Hide Arm/Group Description:
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Overall Number of Participants Analyzed 170 171 174 172
Least Squares Mean (Standard Error)
Unit of Measure: percentage of vaginal parabasal cells
-40.63  (1.755) -44.07  (1.751) -45.55  (1.745) -6.73  (1.750)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
3.Primary Outcome
Title Co-Primary Efficacy Endpoint - Vaginal pH
Hide Description • Change from Baseline to Week 12 in vaginal pH as compared to placebo
Time Frame Baseline and 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo
Hide Arm/Group Description:
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Overall Number of Participants Analyzed 170 171 174 174
Least Squares Mean (Standard Error)
Unit of Measure: pH units
-1.32  (0.066) -1.42  (0.066) -1.34  (0.066) -0.28  (0.066)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
4.Primary Outcome
Title Co-Primary Efficacy Endpoint - Severity of Most Bothersome Symptom (Dyspareunia)
Hide Description

• Change from Baseline to Week 12 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 12

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo
Hide Arm/Group Description:
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Postmenopausal women self-administered intravaginally one capsule daily for 14 days and then bi-weekly for 10 weeks.
Overall Number of Participants Analyzed 151 154 159 163
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.52  (0.071) -1.69  (0.071) -1.69  (0.071) -1.28  (0.070)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0149
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
5.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Superficial Cells
Hide Description • Change from Baseline to Week 2 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 186 188 184 185
Least Squares Mean (Standard Error)
Unit of Measure: percentage of vaginal superficial cells
31.35  (1.496) 31.93  (1.488) 38.85  (1.500) 6.05  (1.498)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
6.Secondary Outcome
Title Secondary Efficacy Endpoints- Vaginal Superficial Cells
Hide Description Change from Baseline to Week 6 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 172 170 173 176
Least Squares Mean (Standard Error)
Unit of Measure: percentage of vaginal superficial cells
18.41  (1.536) 16.88  (1.543) 22.65  (1.532) 5.43  (1.525)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
7.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Superficial Cells
Hide Description Change from Baseline to Week 8 in the percentage of vaginal superficial cells (by vaginal cytologic smear) compared to placebo
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 164 165 166 167
Least Squares Mean (Standard Error)
Unit of Measure: percentage of vaginal superficial cells
19.04  (1.561) 17.41  (1.558) 23.88  (1.554) 5.98  (1.551)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
8.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Parabasal Cells
Hide Description Change from Baseline to Week 2 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 186 188 184 185
Least Squares Mean (Standard Error)
Unit of Measure: percentage of vaginal parabasal cells
-40.23  (1.720) -44.42  (1.710) -45.60  (1.723) -7.00  (1.720)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
9.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Parabasal Cells
Hide Description Change from Baseline to Week 6 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 172 170 173 176
Least Squares Mean (Standard Error)
Unit of Measure: percentage of vaginal parabasal cells
-39.36  (1.750) -43.55  (1.752) -45.61  (1.746) -9.23  (1.741)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
10.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Parabasal Cells
Hide Description Change from Baseline to Week 8 in the percentage of vaginal parabasal cells (by vaginal cytologic smear) compared to placebo
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 164 165 166 167
Least Squares Mean (Standard Error)
Unit of Measure: percentage of vaginal parabasal cells
-41.87  (1.768) -43.78  (1.764) -45.08  (1.762) -7.86  (1.760)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
11.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal pH
Hide Description Change from Baseline to Week 2 in vaginal pH as compared to placebo
Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 186 188 184 186
Least Squares Mean (Standard Error)
Unit of Measure: pH units
-1.23  (0.064) -1.37  (0.064) -1.30  (0.065) -0.28  (0.064)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
12.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal pH
Hide Description Change from Baseline to Week 6 in vaginal pH as compared to placebo
Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 172 170 173 176
Least Squares Mean (Standard Error)
Unit of Measure: pH units
-1.32  (0.066) -1.40  (0.066) -1.48  (0.066) -0.30  (0.065)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
13.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal pH
Hide Description Change from Baseline to Week 8 in vaginal pH as compared to placebo
Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 164 165 166 167
Least Squares Mean (Standard Error)
Unit of Measure: pH units
-1.35  (0.067) -1.46  (0.067) -1.45  (0.066) -0.38  (0.066)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
14.Secondary Outcome
Title Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)
Hide Description

Change from Baseline to Week 2 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 2

Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 145 147 140 141
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.99  (0.072) -1.08  (0.072) -1.02  (0.073) -0.76  (0.072)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0260
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0105
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
15.Secondary Outcome
Title Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)
Hide Description

Change from Baseline to Week 6 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 6

Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 148 150 150 159
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.30  (0.072) -1.37  (0.072) -1.48  (0.072) -1.03  (0.070)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0069
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
16.Secondary Outcome
Title Secondary Efficacy Endpoints - Severity of Most Bothersome Symptom (Dyspareunia)
Hide Description

Change from Baseline to Week 8 on the severity of the MBS of dyspareunia (vaginal pain associated with sexual activity) associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 8

Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 140 136 129 143
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.52  (0.073) -1.64  (0.074) -1.62  (0.075) -1.15  (0.072)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
17.Secondary Outcome
Title Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)
Hide Description

Change from Baseline to Week 2 on the severity of vaginal dryness associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 2

Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 186 188 184 185
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.86  (0.066) -1.01  (0.065) -0.96  (0.066) -0.72  (0.066)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1269
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0082
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
18.Secondary Outcome
Title Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)
Hide Description

Change from Baseline to Week 6 on the severity of vaginal dryness associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 6

Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 172 170 172 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.14  (0.067) -1.27  (0.068) -1.23  (0.067) -0.90  (0.067)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0094
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
19.Secondary Outcome
Title Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)
Hide Description

Change from Baseline to Week 8 on the severity of vaginal dryness associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 8

Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 163 165 165 167
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.25  (0.069) -1.44  (0.068) -1.34  (0.068) -1.01  (0.068)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0128
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
20.Secondary Outcome
Title Secondary Efficacy Endpoints - Severity of Other VVA Symptoms (Vaginal Dryness)
Hide Description

Change from Baseline to Week 12 on the severity of vaginal dryness associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 12

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 171 173 176 174
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.27  (0.068) -1.47  (0.067) -1.47  (0.067) -0.97  (0.067)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
21.Secondary Outcome
Title Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)
Hide Description

Change from Baseline to Week 2 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 2

Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 186 188 184 185
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.47  (0.054) -0.56  (0.053) -0.51  (0.054) -0.47  (0.054)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9616
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2439
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6518
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
22.Secondary Outcome
Title Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)
Hide Description

Change from Baseline to Week 6 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 6

Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 172 170 172 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.57  (0.055) -0.64  (0.055) -0.61  (0.055) -0.55  (0.055)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7829
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2328
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4118
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
23.Secondary Outcome
Title Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)
Hide Description

Change from Baseline to Week 8 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 8

Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 163 165 165 167
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.74  (0.056) -0.76  (0.056) -0.73  (0.056) -0.59  (0.056)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0639
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0356
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0914
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
24.Secondary Outcome
Title Secondary Efficacy Endpoints - Other VVA Symptoms (Vulvar and/or Vaginal Itching or Irritation)
Hide Description

Change from Baseline to Week 12 on the severity of vulvar and/or vaginal itching or irritation associated with VVA as compared to placebo

VVA Symptoms Self-Assessment Questionnaire Severity Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe.

Subjects assessed severity at Baseline and Week 12

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 171 173 176 174
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.75  (0.055) -0.81  (0.055) -0.77  (0.055) -0.60  (0.055)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0503
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0263
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
25.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)
Hide Description

Change from Baseline to Week 2 in Vaginal Color as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 2

Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 185 187 184 187
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.69  (0.048) -0.77  (0.047) -0.78  (0.048) -0.40  (0.047)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
26.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)
Hide Description

Change from Baseline to Week 6 in Vaginal Color as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 6

Time Frame Baseline to Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 172 170 173 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.82  (0.049) -0.93  (0.049) -0.89  (0.049) -0.50  (0.048)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
27.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)
Hide Description

Change from Baseline to Week 8 in Vaginal Color as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 8

Time Frame Baseline to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 164 165 166 167
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.98  (0.050) -1.04  (0.050) -0.99  (0.049) -0.50  (0.049)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
28.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Color)
Hide Description

Change from Baseline to Week 12 in Vaginal Color as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Color: No atrophy (pink) = 0; Mild (lighter in color) = 1; Moderate(pale in color) = 2; Severe (transparent/no color or inflamed) = 3 Severity was assessed by the Investigator at Baseline and Week 12

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 171 173 175 175
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.97  (0.049) -1.06  (0.049) -0.96  (0.049) -0.60  (0.049)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
29.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)
Hide Description

Change from Baseline to Week 2 in Vaginal Epithelial Integrity as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

Severity was assessed by the Investigator at Baseline and Week 2

Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 185 187 184 186
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.85  (0.049) -0.87  (0.049) -0.93  (0.049) -0.53  (0.049)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
30.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)
Hide Description

Change from Baseline to Week 6 in Vaginal Epithelial Integrity as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

Severity was assessed by the Investigator at Baseline and Week 6

Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 172 170 173 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.97  (0.051) -1.02  (0.051) -1.01  (0.051) -0.61  (0.050)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
31.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)
Hide Description

Change from Baseline to Week 8 in Vaginal Epithelial Integrity as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

Severity was assessed by the Investigator at Baseline and Week 8

Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 164 165 166 167
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.03  (0.052) -1.08  (0.051) -1.08  (0.051) -0.66  (0.051)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
32.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Integrity)
Hide Description

Change from Baseline to Week 12 in Vaginal Epithelial Integrity as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Integrity: No atrophy (normal) = 0; Mild (vaginal surface bleeds with scraping) = 1; Moderate (vaginal surface bleeds with light contact) = 2; Severe (vaginal surface has petechiae before contact and bleeds with light contact) = 3

Severity was assessed by the Investigator at Baseline and Week 12

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 171 173 175 175
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.97  (0.051) -1.07  (0.051) -1.01  (0.050) -0.60  (0.050)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
33.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)
Hide Description

Change from Baseline to Week 2 in Vaginal Epithelial Surface Thickness as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

Severity was assessed by the Investigator at Baseline and Week 2

Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 185 187 184 186
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.76  (0.049) -0.76  (0.049) -0.76  (0.049) -0.40  (0.049)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
34.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)
Hide Description

Change from Baseline to Week 6 in Vaginal Epithelial Surface Thickness as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

Severity was assessed by the Investigator at Baseline and Week 6

Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 172 170 173 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.85  (0.051) -0.93  (0.051) -0.90  (0.050) -0.53  (0.050)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
35.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)
Hide Description

Change from Baseline to Week 8 in Vaginal Epithelial Surface Thickness as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

Severity was assessed by the Investigator at Baseline and Week 8

Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 164 165 166 167
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.96  (0.051) -1.04  (0.051) -0.99  (0.051) -0.59  (0.051)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
36.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Epithelial Surface Thickness)
Hide Description

Change from Baseline to Week 12 in Vaginal Epithelial Surface Thickness as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Epithelial Surface Thickness: No atrophy (rogation and elasticity of vault) = 0; Mild (poor rogation with some elasticity noted of vaginal vault) = 1; Moderate (smooth, some elasticity of vaginal vault) = 2; Severe [smooth, no elasticity, constriction of the upper one third of vagina or loss of vaginal tone (cystocele and rectocele)] = 3

Severity was assessed by the Investigator at Baseline and Week 12

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 12 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 171 173 175 175
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.98  (0.051) -1.03  (0.051) -0.94  (0.050) -0.61  (0.050)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
37.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)
Hide Description

Change from Baseline to Week 2 in Vaginal Secretions as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain) = 3

Severity was assessed by the Investigator at Baseline and Week 2

Time Frame Baseline and Week 2
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 2 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 185 187 184 186
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.79  (0.050) -0.83  (0.050) -0.86  (0.050) -0.54  (0.050)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
38.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)
Hide Description

Change from Baseline to Week 6 in Vaginal Secretions as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3

Severity was assessed by the Investigator at Baseline and Week 6

Time Frame Baseline and Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 6 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 172 170 173 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.90  (0.051) -0.95  (0.051) -0.97  (0.051) -0.60  (0.051)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
39.Secondary Outcome
Title Secondary Efficacy Endpoints - Vaginal Mucosa Assessment (Vaginal Secretions)
Hide Description

Change from Baseline to Week 8 in Vaginal Secretions as compared to placebo

Vaginal Mucosa Assessment Scale - Vaginal Secretions: No atrophy (normal clear secretions noted on vaginal walls) = 0; Mild (superficial coating of secretions, difficulty with speculum insertion) = 1; Moderate (scant not covering the entire vaginal vault, may need lubrication with speculum insertion to prevent pain) = 2; Severe (none, inflamed, ulceration noted, need lubrication with speculum insertion to prevent pain] = 3

Severity was assessed by the Investigator at Baseline and Week 8

Time Frame Baseline and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
For the statistical test utilized (MMRM), the number of subjects analyzed varied based on if they had both Baseline and Week 8 data so it would not necessarily match the overall number of subjects in the MITT Population at Baseline.
Arm/Group Title Estradiol 4mcg Vaginal Softgel Capsule Estradiol 10mcg Vaginal Softgel Capsule Estradiol 25mcg Vaginal Softgel Capsule Placebo Vaginal Softgel Capsule
Hide Arm/Group Description:

Estradiol 4mcg Vaginal Softgel Capsule

Estradiol

Estradiol 10mcg Vaginal Softgel Capsule

Estradiol

Estradiol 25mcg Vaginal Softgel Capsule

Estradiol

Placebo Vaginal Softgel Capsule

Placebo

Overall Number of Participants Analyzed 164 165 166 167
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.00  (0.052) -1.04  (0.052) -1.06  (0.052) -0.63  (0.052)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Estradiol 4mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Estradiol 10mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Estradiol 25mcg Vaginal Softgel Capsule, Placebo Vaginal Softgel Capsule
Comments [Not Specified]