A Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms (REPLENISH)

• ClinicalTrials.gov Identifier: NCT01942668
• Recruitment Status: Completed
• First Posted: September 16, 2013
• Results First Posted: May 6, 2019
• Last Update Posted: May 6, 2019
• Sponsor: TherapeuticsMD
• Information provided by (Responsible Party): TherapeuticsMD

Study Description

Brief Summary:

This study will be a prospective, randomized, double-blind, placebo-controlled, parallel group, multicenter trial of postmenopausal subjects with an intact uterus.

Condition or disease	Intervention/treatment	Phase
Menopause	Drug: Estradiol; Drug: Progesterone; Drug: Placebo	Phase 3

Detailed Description:

Postmenopausal subjects with an intact uterus who meet the study entry criteria will be randomized to one of five treatment arms (four active and one placebo) and followed for 12 months. During the Screening period all subjects will be provided with a diary to self-assess the frequency and severity of their vasomotor symptoms. Subjects experiencing a minimum daily frequency of ≥7 (or ≥50 per week) moderate to severe hot flushes will participate in a VMS Substudy during the first 12 weeks of treatment. The Substudy subjects will be stratified by treatment arm within the sites, and only Substudy subjects have the possibility of being randomized to placebo. Subjects who qualify for the study except for experiencing a minimum daily frequency of ≥7 (or ≥50 per week) moderate to severe hot flushes will be stratified within sites to one of the four active treatment arms and followed for 12 months, but will not participate in the VMS Substudy. (However, VMS information will be collected from all subjects during the first 12 weeks of treatment.) All Study Subjects: Postmenopausal women with an intact uterus who seek relief from hot flushes and meet all other inclusion/exclusion criteria are eligible for 12 months of study treatment.

VMS Substudy Subjects: A subset of All Study Subjects who have ≥7 per day or ≥50 per week moderate to severe hot flushes (as determined during Screening) are eligible for the 12-week VMS Substudy and for a total of 12 months of study treatment.

Clinical evaluations will be performed at the following time points:

• Screening Period (Week: - 8.5) (up to -60 Days)
• Visit 1 Randomization (Week 0) (Day 1)
• Visit 2 Interim (Week 4)
• Visit 3 Interim (Week 8)
• Visit 4 Interim (Week 12)
• Visit 5 Interim (Month 6)
• Visit 6 Interim (Month 9)
• Visit 7 End of Treatment (Month 12)

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1845 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms in Postmenopausal Women With an Intact Uterus
• Actual Study Start Date: August 5, 2013
• Actual Primary Completion Date: October 28, 2016
• Actual Study Completion Date: October 28, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment 1; Combined Estradiol 1 mg / Progesterone 100 mg softgel capsule formulation and placebo taken orally once a day for twelve months.	Drug: Estradiol; Other Names: 17B-estradiol; Estrace; Drug: Progesterone; Other Name: Prometrium; Drug: Placebo
Experimental: Treatment 2; Combined Estradiol 0.5 mg / Progesterone 100 mg softgel capsule formulation and placebo taken orally once a day for twelve months.	Drug: Estradiol; Other Names: 17B-estradiol; Estrace; Drug: Progesterone; Other Name: Prometrium; Drug: Placebo
Experimental: Treatment 3; Combined Estradiol 0.5 mg / Progesterone 50 mg softgel capsule formulation and placebo, taken orally once a day for twelve months.	Drug: Estradiol; Other Names: 17B-estradiol; Estrace; Drug: Progesterone; Other Name: Prometrium; Drug: Placebo
Experimental: Treatment 4; Combined Estradiol 0.25 mg / Progesterone 50 mg softgel capsule formulation and placebo, taken orally once a day for twelve months.	Drug: Estradiol; Other Names: 17B-estradiol; Estrace; Drug: Progesterone; Other Name: Prometrium; Drug: Placebo
Placebo Comparator: Placebo; Two Placebo softgel capsules taken orally once a day for twelve months.	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
2. Co-Primary Efficacy Endpoint: Frequency of Moderate to Severe Vasomotor Symptoms (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
3. Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
   Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
4. Co-Primary Efficacy Endpoint: Severity of Moderate to Severe Vasomotor Symptoms (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
   Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
5. Primary Safety Endpoint: Endometrial Protection - Hyperplasia [ Time Frame: Baseline and Month 12 ]
   Endometrial biopsies centrally evaluated by 2 primary pathologists using criteria from Blaustein's Pathology text. Pathologists classified bx into 1 of following 3 categories: Cat.1: Non-endometrial malignancy/non-hyperplasia; Cat.2: Endometrial hyperplasia; Cat.3: Endometrial malignancy. Consensus reached when 2 primary pathologist agreed on any of above categories; if primary pathologists disagreed on presence of hyperplasia, result of 3rd pathologist was utilized and final decision regarding presence of hyperplasia was based on diagnosis of majority. If all 3 reads disparate, final diagnosis based on most severe dx. Incidence rate calculated as: I=A/B where I=incidence rate at M12 evaluation, A=all new subjects with biopsies positive for endometrial hyperplasia during study but post-Baseline, B=all subjects w/biopsies following M11 meeting criteria specified plus all subjects w/biopsies positive for endometrial hyperplasia by any pathologists before M11.

Secondary Outcome Measures :

1. Endometrial Protection - Hyperplasia [ Time Frame: Baseline and Month 12 ]
   Endometrial biopsies centrally evaluated by 3 primary pathologists using criteria described in Blaustein's Pathology text. Pathologists classified biopsy into 1 of following 3 categories: Cat.1: Non-endometrial malignancy/non-hyperplasia; Cat.2: Endometrial hyperplasia; Cat.3: Endometrial malignancy. Consensus was reached when the 2 of 3 pathologist readers agreed on any of the above categories; if all three reads were disparate, the final diagnosis was based on the most severe diagnosis. Incidence rate calculated as: I=A/B where I=incidence rate at M12 evaluation, A=all new subjects with biopsies positive for endometrial hyperplasia during study but post-Baseline, B=all subjects with biopsies following M11 meeting the criteria specified plus all subjects with biopsies positive for endometrial hyperplasia by any of the pathologists before M11.
2. Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS) [ Time Frame: Baseline and Week 1 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
3. Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS) [ Time Frame: Baseline and Week 2 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
4. Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS) [ Time Frame: Baseline and Week 3 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
5. Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
6. Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS) [ Time Frame: Baseline and Week 5 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
7. Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS) [ Time Frame: Baseline and Week 6 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
8. Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS) [ Time Frame: Baseline and Week 7 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
9. Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS) [ Time Frame: Baseline and Week 8 ]
   Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
10. Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS) [ Time Frame: Baseline and Week 9 ]
    Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
11. Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS) [ Time Frame: Baseline and Week 10 ]
    Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
12. Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS) [ Time Frame: Baseline and Week 11 ]
    Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
13. Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
    Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of moderate to severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of moderate to severe hot flushes for the subject week.
14. Severity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS) [ Time Frame: Baseline and Week 1 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
15. Severity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS) [ Time Frame: Baseline and Week 2 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
16. Severity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS) [ Time Frame: Baseline and Week 3 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
17. Severity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
18. Severity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS) [ Time Frame: Baseline and Week 5 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
19. Severity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS) [ Time Frame: Baseline and Week 6 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
20. Severity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS) [ Time Frame: Baseline and Week 7 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
21. Severity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS) [ Time Frame: Baseline and Week 8 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
22. Severity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS) [ Time Frame: Baseline and Week 9 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
23. Severity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS) [ Time Frame: Baseline and Week 10 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
24. Severity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS) [ Time Frame: Baseline and Week 11 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
25. Severity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
    Mean change in severity of moderate to severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score = (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of moderate to severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
26. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS) [ Time Frame: Baseline and Week 1 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
27. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS) [ Time Frame: Baseline and Week 2 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
28. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS) [ Time Frame: Baseline and Week 3 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
29. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
30. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS) [ Time Frame: Baseline and Week 5 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
31. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS) [ Time Frame: Baseline and Week 6 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
32. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS) [ Time Frame: Baseline and Week 7 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
33. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS) [ Time Frame: Baseline and Week 8 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
34. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS) [ Time Frame: Baseline and Week 9 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
35. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS) [ Time Frame: Baseline and Week 10 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
36. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS) [ Time Frame: Baseline and Week 11 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
37. Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
    Mean change in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The weekly frequency of mild, moderate and severe hot flushes was calculated from the daily diary record using a forward counting process of 7 day intervals beginning with the baseline date. Weekly frequency equals total number of mild, moderate and severe hot flushes for the subject week.
38. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS) [ Time Frame: Baseline and Week 1 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 1. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
39. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS) [ Time Frame: Baseline and Week 2 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 2. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
40. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS) [ Time Frame: Baseline and Week 3 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 3. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
41. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 4. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
42. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS) [ Time Frame: Baseline and Week 5 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 5. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
43. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS) [ Time Frame: Baseline and Week 6 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 6. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
44. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS) [ Time Frame: Baseline and Week 7 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 7. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
45. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS) [ Time Frame: Baseline and Week 8 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 8. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
46. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS) [ Time Frame: Baseline and Week 9 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 9. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
47. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS) [ Time Frame: Baseline and Week 10 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 10. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
48. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS) [ Time Frame: Baseline and Week 11 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 11. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
49. Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
    Mean change in severity of mild, moderate and severe vasomotor symptoms at Baseline to mild, moderate to severe vasomotor symptoms at Week 12. The baseline was the most recent 7 consecutive days of data prior to randomization. The severity score was derived as follows: mild = 1, moderate = 2, severe = 3. Baseline Weekly Severity Score =(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days). On Treatment Weekly Severity Score = [(number of mild hot flushes for 7 days) x 1 + (number of moderate hot flushes for 7 days) x 2 + (number of severe hot flushes for 7 days) x 3] / (total number of mild, moderate and severe hot flushes over 7 days).
50. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS) [ Time Frame: Baseline and Week 1 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe VMS from Baseline to Week 1.
51. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS) [ Time Frame: Baseline and Week 2 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 2.
52. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS) [ Time Frame: Baseline and Week 3 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 3.
53. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4.
54. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS) [ Time Frame: Baseline and Week 5 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 5.
55. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS) [ Time Frame: Baseline and Week 6 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 6.
56. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS) [ Time Frame: Baseline and Week 7 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 7.
57. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS) [ Time Frame: Baseline and Week 8 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8.
58. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS) [ Time Frame: Baseline and Week 9 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 9.
59. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS) [ Time Frame: Baseline and Week 10 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 10.
60. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS) [ Time Frame: Baseline and Week 11 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 11.
61. Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12.
62. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS) [ Time Frame: Baseline and Week 1 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 1.
63. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS) [ Time Frame: Baseline and Week 2 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 2.
64. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS) [ Time Frame: Baseline and Week 3 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 3.
65. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 4.
66. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS) [ Time Frame: Baseline and Week 5 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 5.
67. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS) [ Time Frame: Baseline and Week 6 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 6.
68. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS) [ Time Frame: Baseline and Week 7 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 7.
69. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS) [ Time Frame: Baseline and Week 8 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 8.
70. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS) [ Time Frame: Baseline and Week 9 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 9.
71. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS) [ Time Frame: Baseline and Week 10 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 10.
72. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS) [ Time Frame: Baseline and Week 11 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 11.
73. Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
    Number of Subjects with >=50%, and separately, >=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 12.
74. Clinical Global Impression (CGI) - Week 4 (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
    The number and percentage of subjects for each possible response to the CGI at Week 4. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
75. Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS) [ Time Frame: Baseline and Week 4 ]
    Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4 for the respective CGI category. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
76. Clinical Global Impression (CGI) - Week 8 (MITT-VMS) [ Time Frame: Baseline and Week 8 ]
    The number and percentage of subjects for each possible response to the CGI at Week 8. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
77. Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS) [ Time Frame: Baseline and Week 8 ]
    Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8 for the respective CGI category. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
78. Clinical Global Impression (CGI) - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
    The number and percentage of subjects for each possible response to the CGI at Week 12. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
79. Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
    Mean change in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12 for the respective CGI category. The CGI score is a seven point scale where subjects were asked to rate the total improvement, whether or not in her judgment it was due entirely to drug treatment, compared to her condition at admission to the study. Scale: Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse. Results for the top two responses (Very Much Improved and Much Improved) and No Change or Worsening (Minimally worse, Much worse, Very much worse) were combined for each group and active treatment groups compare to placebo.
80. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 1 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
81. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 2 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
82. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 3 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
83. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 4 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
84. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 5 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
85. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 6 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
86. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 7 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
87. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 8 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
88. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 9 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
89. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 10 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
90. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 11 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
91. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: Cycle 12 to 13 ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
92. Number of Subjects Without Bleeding for Consecutive Cycles [ Time Frame: The 13th Cycle ]
    No bleeding was defined as the absence of bleeding. Cumulative rates for no bleeding was defined as the percentage of women who reported consecutive cycles of no bleeding for a given cycle of time.
93. Number of Subjects With Cumulative Amenorrhea From Cycle 1 to 13 [ Time Frame: Cycle 1 to 13 ]
    Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 1 to 13 was calculated and compared between active and placebo treatments.
94. Number of Subjects With Cumulative Amenorrhea From Cycle 2 to 13 [ Time Frame: Cycle 2 to 13 ]
    Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 2 to 13 was calculated and compared between active and placebo treatments.
95. Number of Subjects With Cumulative Amenorrhea From Cycle 3 to 13 [ Time Frame: Cycle 3 to 13 ]
    Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 3 to 13 was calculated and compared between active and placebo treatments.
96. Number of Subjects With Cumulative Amenorrhea From Cycle 4 to 13 [ Time Frame: Cycle 4 to 13 ]
    Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 4 to 13 was calculated and compared between active and placebo treatments.
97. Number of Subjects With Cumulative Amenorrhea From Cycle 5 to 13 [ Time Frame: Cycle 5 to 13 ]
    Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 5 to 13 was calculated and compared between active and placebo treatments.
98. Number of Subjects With Cumulative Amenorrhea From Cycle 6 to 13 [ Time Frame: Cycle 6 to 13 ]
    Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 6 to 13 was calculated and compared between active and placebo treatments.
99. Number of Subjects With Cumulative Amenorrhea From Cycle 7 to 13 [ Time Frame: Cycle 7 to 13 ]
    Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 7 to 13 was calculated and compared between active and placebo treatments.
100. Number of Subjects With Cumulative Amenorrhea From Cycle 8 to 13 [ Time Frame: Cycle 8 to 13 ]
     Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 8 to 13 was calculated and compared between active and placebo treatments.
101. Number of Subjects With Cumulative Amenorrhea From Cycle 9 to 13 [ Time Frame: Cycle 9 to 13 ]
     Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 9 to 13 was calculated and compared between active and placebo treatments.
102. Number of Subjects With Cumulative Amenorrhea From Cycle 10 to 13 [ Time Frame: Cycle 10 to 13 ]
     Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 10 to 13 was calculated and compared between active and placebo treatments.
103. Number of Subjects With Cumulative Amenorrhea From Cycle 11 to 13 [ Time Frame: Cycle 11 to 13 ]
     Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 11 to 13 was calculated and compared between active and placebo treatments.
104. Number of Subjects With Cumulative Amenorrhea From Cycle 12 to 13 [ Time Frame: Cycle 12 to 13 ]
     Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from Cycle 12 to 13 was calculated and compared between active and placebo treatments.
105. Number of Subjects With Cumulative Amenorrhea From the 13th Cycle [ Time Frame: The 13th Cycle ]
     Cumulative amenorrhea is defined as the absence of bleeding or spotting for a cumulative period. Cumulative rates of amenorrhea were defined as the percentage of women who reported consecutive cycles of amenorrhea for a given cycle of time. Within each treatment arm, the percentage of subjects with cumulative amenorrhea from the 13th Cycle was calculated and compared between active and placebo treatments.
106. Subject Incidence With Spotting - Trimester 1 (Safety Pop.) [ Time Frame: Trimester 1 ]
     Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
107. Subject Incidence With Spotting - Trimester 2 (Safety Pop.) [ Time Frame: Trimester 2 ]
     Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
108. Subject Incidence With Spotting - Trimester 3 (Safety Pop.) [ Time Frame: Trimester 3 ]
     Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
109. Subject Incidence With Spotting - Trimester 4 (Safety Pop.) [ Time Frame: Trimester 4 ]
     Summary of subject incidence with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
110. Number of Days With Spotting - Trimester 1 (Safety Pop.) [ Time Frame: Trimester 1 ]
     Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
111. Number of Days With Spotting - Trimester 2 (Safety Pop.) [ Time Frame: Trimester 2 ]
     Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
112. Number of Days With Spotting - Trimester 3 (Safety Pop.) [ Time Frame: Trimester 3 ]
     Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
113. Number of Days With Spotting - Trimester 4 (Safety Pop.) [ Time Frame: Trimester 4 ]
     Summary of the number of days with spotting per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
114. Subject Incidence With Bleeding - Trimester 1 (Safety Pop.) [ Time Frame: Trimester 1 ]
     Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
115. Subject Incidence With Bleeding - Trimester 2 (Safety Pop.) [ Time Frame: Trimester 2 ]
     Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
116. Subject Incidence With Bleeding - Trimester 3 (Safety Pop.) [ Time Frame: Trimester 3 ]
     Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
117. Subject Incidence With Bleeding - Trimester 4 (Safety Pop.) [ Time Frame: Trimester 4 ]
     Summary of subject incidence with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
118. Number of Days With Bleeding - Trimester 1 (Safety Pop.) [ Time Frame: Trimester 1 ]
     Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
119. Number of Days With Bleeding - Trimester 2 (Safety Pop.) [ Time Frame: Trimester 2 ]
     Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
120. Number of Days With Bleeding - Trimester 3 (Safety Pop.) [ Time Frame: Trimester 3 ]
     Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
121. Number of Days With Bleeding - Trimester 4 (Safety Pop.) [ Time Frame: Trimester 4 ]
     Summary of the number of days with bleeding per trimester as recorded in a daily diary. A trimester is defined as every 90 days since Day 1.
122. Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Changes in Vasomotor Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being "not at all bothered" and 8 being "extremely bothered".
123. Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Changes in Vasomotor Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being "not at all bothered" and 8 being "extremely bothered".
124. Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Changes in Vasomotor Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being "not at all bothered" and 8 being "extremely bothered".
125. Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Changes in Psychosocial Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being "not at all bothered" and 8 being "extremely bothered".
126. Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Changes in Psychosocial Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being "not at all bothered" and 8 being "extremely bothered".
127. Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Changes in Psychosocial Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being "not at all bothered" and 8 being "extremely bothered".
128. Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Changes in Physical Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being "not at all bothered" and 8 being "extremely bothered".
129. Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Changes in Physical Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being "not at all bothered" and 8 being "extremely bothered".
130. Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Changes in Physical Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being "not at all bothered" and 8 being "extremely bothered".
131. Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Changes in Sexual Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being "not at all bothered" and 8 being "extremely bothered".
132. Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Changes in Sexual Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being "not at all bothered" and 8 being "extremely bothered".
133. Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Changes in Sexual Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being "not at all bothered" and 8 being "extremely bothered".
134. Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Changes in Overall Scores from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being "not at all bothered" and 8 being "extremely bothered".
135. Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Changes in Overall Scores from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being "not at all bothered" and 8 being "extremely bothered".
136. Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Changes in Overall Scores from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being "not at all bothered" and 8 being "extremely bothered".
137. Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
138. Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
139. Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
140. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
141. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
142. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
143. Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
144. Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
145. Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
146. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
147. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
148. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
149. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS_4_new = (6-MOS_4_old) x 20; MOS_12_new = (6-MOS_12_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
150. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS_4_new = (6-MOS_4_old) x 20; MOS_12_new = (6-MOS_12_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
151. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS_4_new = (6-MOS_4_old) x 20; MOS_12_new = (6-MOS_12_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
152. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
153. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
154. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
155. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
156. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
157. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
158. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
159. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
160. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
161. Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline (BL) to Week 12 in MOS Optimal Sleep Score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where >0 = overall improvement and <0 = overall worsening in the study arm.
162. Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline (BL) to Month 6 in MOS Optimal Sleep Score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where >0 = overall improvement and <0 = overall worsening in the study arm.
163. Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline (BL) to Month 12 in MOS Optimal Sleep Score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where >0 = overall improvement and <0 = overall worsening in the study arm.
164. Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT) [ Time Frame: Baseline and Week 12 ]
     Changes in Vasomotor Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being "not at all bothered" and 8 being "extremely bothered".
165. Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT) [ Time Frame: Baseline and Month 6 ]
     Changes in Vasomotor Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being "not at all bothered" and 8 being "extremely bothered".
166. Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT) [ Time Frame: Baseline and Month 12 ]
     Changes in Vasomotor Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Vasomotor domain score is mean of = Q1,Q2, Q3, with 1 being "not at all bothered" and 8 being "extremely bothered".
167. Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT) [ Time Frame: Baseline and Week 12 ]
     Changes in Psychosocial Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being "not at all bothered" and 8 being "extremely bothered".
168. Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT) [ Time Frame: Baseline and Month 6 ]
     Changes in Psychosocial Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being "not at all bothered" and 8 being "extremely bothered".
169. Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT) [ Time Frame: Baseline and Month 12 ]
     Changes in Psychosocial Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Psychosocial domain score is mean of = Q4 to Q10, with 1 being "not at all bothered" and 8 being "extremely bothered".
170. Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT) [ Time Frame: Baseline and Week 12 ]
     Changes in Physical Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being "not at all bothered" and 8 being "extremely bothered".
171. Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT) [ Time Frame: Baseline and Month 6 ]
     Changes in Physical Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being "not at all bothered" and 8 being "extremely bothered".
172. Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT) [ Time Frame: Baseline and Month 12 ]
     Changes in Physical Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Physical domain score is mean of = Q11 to Q26, with 1 being "not at all bothered" and 8 being "extremely bothered".
173. Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT) [ Time Frame: Baseline and Week 12 ]
     Changes in Sexual Domain Score from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being "not at all bothered" and 8 being "extremely bothered".
174. Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT) [ Time Frame: Baseline and Month 6 ]
     Changes in Sexual Domain Score from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being "not at all bothered" and 8 being "extremely bothered".
175. Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT) [ Time Frame: Baseline and Month 12 ]
     Changes in Sexual Domain Score from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The scale contains four domains: vasomotor, psychosocial, physical and sexual. Each domain is scored separately. Sexual domain score is mean of = Q27 to Q29, with 1 being "not at all bothered" and 8 being "extremely bothered".
176. Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT) [ Time Frame: Baseline and Week 12 ]
     Change in Overall Scores from Baseline to Week 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being "not at all bothered" and 8 being "extremely bothered".
177. Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT) [ Time Frame: Baseline and Month 6 ]
     Change in Overall Scores from Baseline to Month 6. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being "not at all bothered" and 8 being "extremely bothered".
178. Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT) [ Time Frame: Baseline and Month 12 ]
     Change in Overall Scores from Baseline to Month 12. The MENQOL is self-administered questionnaire which assessed changes in quality of life over a one-month period. It is composed of 29 questions indicating if subject experienced the problem (Yes/No) and if Yes, rating scale ranged from 0=Not bothered at all to 6=Extremely bothered. The scale contains four domains: vasomotor, psychosocial, physical and sexual. For analysis, the original scores were converted to the analysis score ranging from 1-8 where No=1, 0=2, 1=3...and 6=8. The Overall Score is the mean of the 4 domain scores with 1 being "not at all bothered" and 8 being "extremely bothered".
179. Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
180. Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
181. Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Total Sleep Score as compared w/Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Total score includes items Q1, 3, 4, 5, 6, 7, 8, 9, & 12. Scoring method: Answers to Q3, 5, 6, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q1, 4, & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Total score= average of item scores; ranges =0 to 100, where higher score means worse outcome. If any of individual questions used to obtain total score is missing, total score will be set to missing value.
182. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
183. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
184. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Disturbance individual score as compared with Placebo. MOS-Sleep Self Report Questionnaire is 12 items that measure 6 dimensions of sleep over past 4 wks. Q1 scored on scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 self-reported hrs of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep disturbance includes items Q1, Q3, Q7, Q8. Scoring method: Answer to Q1 is rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25. Answers to Q3, 7, 8 are reversed & rescaled to realign to be same direction and range(0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Score is average of item scores; score range=0 to 100, where higher score means worse outcome.
185. Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
186. Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
187. Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Snoring individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Snoring item is Q10. Scoring method: Answer to Q10 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
188. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
189. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
190. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Short of Breath or Headache(SOBHA) individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. SOBHA item is Q5. Scoring method: Answer to Q5 is reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score range=0 to 100, where higher score means worse outcome.
191. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS_4_new = (6-MOS_4_old) x 20; MOS_12_new = (6-MOS_12_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
192. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS_4_new = (6-MOS_4_old) x 20; MOS_12_new = (6-MOS_12_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
193. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Adequacy individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Adequacy includes items Q4, Q12. Scoring method: Answers for Q4 and Q12 are reversed and rescaled to 0-100 as follows: MOS_4_new = (6-MOS_4_old) x 20; MOS_12_new = (6-MOS_12_old) x 20. Score is the average of item scores; score range = 0 to 100, where higher score means better outcome.
194. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
195. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
196. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Somnolence individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-Q12 are scored 1-6 ranging from 1=All of the time to 6=None of the time. Sleep Somnolence items include Q6, Q9, Q11. Scoring method: Answers to Q6, Q 9 and Q11 are reversed & rescaled to 0 to 100 such that 0="best possible" & 100="worst possible". MOS_n_new <- (6-MOS_n_old) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
197. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
198. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
199. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Problems Index I individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self-reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index I includes items Q4, Q5, Q7, Q8, Q9, Q12. Scoring method: Answers to Q, 5, 7, 8, 9 are reversed & rescaled to realign to be same direction and range (0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20. Answers to Q4, & 12 are rescaled to 0-100 as follows: MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
200. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline to Wk 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
201. Medical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline to Month 6 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
202. Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline to Month 12 in MOS Sleep Problems Index II individual score as compared with Placebo. The MOS-Sleep Self Report Questionnaire is composed of 12 items that measure 6 dimensions of sleep over the past 4 weeks. Q1 is scored on a scale 1-5: 1=0-15 min, 2=16-30 min...5=>60 mins. Q2 is self reported hours of sleep per night. Q3-12 scored 1-6 where 1=All of the time to 6=None of the time. Sleep Problems Index II items include Q1, Q3, Q4, Q5, Q6, Q7, Q8, Q9, Q12. Scoring method: Answers to Q3, 5, 6, 7, 8, & 9 are reversed & rescaled to realign to be same direction and range 0 to 100 with 0="best possible" & 100="worst possible" as follows: MOS_n_new = (6-MOS_n_old) x 20, for n=Q3, 5, 6, 7, 8, and 9. Answers to Q1, 4 & 12 are rescaled to 0-100 as follows: MOS_1_new =(MOS_1_old - 1) x 25; MOS_4_new =(MOS_4_old - 1) x 20; MOS_12_new=(MOS_12_old - 1) x 20. Score is the average of item scores; score range range=0 to 100, where higher score means worse outcome.
203. Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT) [ Time Frame: Baseline and Week 12 ]
     Change from Baseline (BL) to Wk 12 in MOS Optimal Sleep Score as compared with Placebo.The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where >0 = overall improvement and <0 = overall worsening in the study arm.
204. Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT) [ Time Frame: Baseline and Month 6 ]
     Change from Baseline (BL) to Month 6 in MOS Optimal Sleep Score as compared with Placebo.The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where >0 = overall improvement and <0 = overall worsening in the study arm.
205. Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT) [ Time Frame: Baseline and Month 12 ]
     Change from Baseline (BL) to Month 12 in MOS Optimal Sleep Score as compared with Placebo.The MOS-Sleep Self Report Questionnaire is composed of 12 items measuring 6 dimensions of sleep over the past 4 wks. Optimal sleep is based on Q2 (self-reported average hrs sleep per night in past 4 wks). Scoring method: hrs of sleep coded 0 (non-optimal) or 1 (optimal) where 1-6 hrs & 9-23 hrs = 0, 7-8 hrs = 1. Change from BL: subject sleeps 7-8 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = -1; subject sleeps 1-6 or 9-23 hrs at BL & 7-8 hrs at follow-up, change = +1; subject sleeps 1-6 or 9-23 hrs at BL & 1-6 or 9-23 hrs at follow-up, change = 0. Mean change from BL: changes are summed to give the Net Total (equivalent to the number subjects w/ improved sleep hrs minus the number subjects w/ worsened sleep hrs), which is divided by the number of subjects to give the mean proportion of net change, where >0 = overall improvement and <0 = overall worsening in the study arm.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Be a female between the ages of 40 and 65 years (at the time of randomization) who is willing to participate in the study, as documented by signing the informed consent form.

2. Be a postmenopausal woman with an intact uterus and a Screening serum estradiol level of ≤50 pg/mL. Postmenopausal is defined herein as:

   1. ≥ 12 months of spontaneous amenorrhea, or
   2. at least 6 months of spontaneous amenorrhea with a Screening serum FSH level of >40 mIU/ml, or
   3. ≥ 6 weeks postsurgical bilateral oophorectomy.
3. Be seeking treatment or relief for vasomotor symptoms associated with menopause.

4. To participate in the VMS Substudy, a subject must also report ≥7 moderate to severe hot flushes per day, or ≥50 per week, at the baseline assessment during Screening (subjects whose hot flushes are less frequent may still participate as non-Substudy subjects.

   Note: A minimum of 14 consecutive days of complete hot flush diary data are required during the baseline assessment at Screening, and these consecutive days must occur within the last 14 days prior to the Randomization visit (not counting the Randomization visit day itself). The most recent 7 consecutive days of data prior to randomization (Day -7 to Day -1) will be used to determine the baseline number of mild, moderate and severe hot flushes for each subject.

5. Have a Body Mass Index (BMI) less than or equal to 34 kg/mP2P. (BMI values should be rounded to the nearest integer [e.g., 34.4 rounds down to 34, while 26.5 rounds up to 27]).
6. Be willing to abstain from using products (other than study medication) that contain estrogen, progestin, or progesterone throughout study participation.

7. Be judged by the principal or sub-investigator physician as being in otherwise generally good health based on a medical evaluation performed during the Screening period prior to the initial dose of study medication. The medical evaluation findings must include:

   1. a normal or non-clinically significant physical examination, including vital signs (sitting blood pressure, heart rate, respiratory rate and temperature). Sitting systolic blood pressure is ≤140 mmHg and diastolic blood pressure ≤90 mmHg at Screening. A subject may be taking up to two antihypertensive medications.
   2. a normal or non-clinically significant pelvic examination.
   3. a mammogram that shows no sign of significant disease (can be performed within previous 6 months prior to initial dose of study medication). Subjects must have a BI-RADS 1 or 2 to enroll in the study. An incomplete mammogram result, i.e. BI-RADS 0, is not acceptable. The site must obtain a copy of the official report for the subject's study file, and it must be verified that the mammogram itself is available if needed for additional assessment.
   4. a normal or non-clinically significant clinical breast examination. An acceptable breast examination is defined as no masses or other findings identified that are suspicious of malignancy.
   5. a normal Screening Papanicolaou ("Pap") smear. (Subjects with findings of atypical glandular cells [AGC], AGUS, ASCUS with high risk HPV type upon reflex testing, LSIL, ASC-H, HSIL, dysplastic cells, or malignant cells must be excluded from randomization.)
   6. an acceptable result from an evaluable Screening endometrial biopsy. The endometrial biopsy reports by the two central pathologists at Screening must each specify one of the following: proliferative endometrium; weakly proliferative endometrium; disordered proliferative pattern; secretory endometrium; endometrial tissue other (including benign, inactive or atrophic fragments of endometrial epithelium, glands, stroma, etc); endometrial tissue insufficient for diagnosis; no endometrium identified; or no tissue identified. However, at least one pathologist must identify sufficient tissue to evaluate the biopsy. Additionally, the endometrial biopsy reports by the two central pathologists of Other Findings at Screening must each specify one of the following: endometrial polyp not present; benign endometrial polyp; or polyp other. (See Exclusion criterion #27)
   7. a normal or non-clinically significant 12-lead ECG.

Exclusion Criteria:

• To participate in the study, a subject must NOT:

  1. Be currently hospitalized.
  2. Have a history of thrombosis of deep veins or arteries or a thromboembolic disorder.
  3. Have a history of coronary artery or cerebrovascular disease (e.g., myocardial infarction, angina, stroke, TIA).
  4. Have a history of a chronic liver or kidney dysfunction/disorder (e.g., Hepatitis C or chronic renal failure).
  5. Have a history of a malabsorption disorder (e.g., gastric bypass, Crohn's disease).
  6. Have a history of gallbladder dysfunction/disorders (e.g., cholangitis, cholecystitis), unless gallbladder has been removed.
  7. Have a history of diabetes, thyroid disease or any other endocrinological disease. (Subjects with diet-controlled diabetes or controlled hypothyroid disease at Screening are not excluded.)
  8. Have a history of estrogen-dependent neoplasia.
  9. Have a history of atypical ductal hyperplasia of the breast.
  10. Have a finding of clinically significant uterine fibroids at Screening.
  11. Have had a uterine ablation.
  12. Have a history of undiagnosed vaginal bleeding.
  13. Have any history of endometrial hyperplasia, melanoma, or uterine/endometrial, breast or ovarian cancer.
  14. Have any history of other malignancy within the last 5 years, with the exception of basal cell (excluded if within 1 year) or non-invasive squamous cell (excluded if within 1 year) carcinoma of the skin.
  15. Have a history of any other cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, psychological (e.g., bipolar disorder, schizophrenia, major depressive disorder), or musculoskeletal disease or disorder that is clinically significant in the opinion of the Principal Investigator or Medical Sub-Investigator.

  16. Have any of the following clinical laboratory values at Screening:

      1. fasting triglyceride of ≥300 mg/dL and/or total cholesterol of ≥300mg/dL
      2. positive laboratory finding for Factor V Leiden mutation
      3. AST or ALT ≥1.5 times the upper limit of normal (ULN)
      4. fasting glucose >125 mg/dL
  17. Be known to be pregnant or have a positive urine pregnancy test. (Note: A pregnancy test is not required for subjects who have had bilateral tubal ligation, bilateral oophorectomy, or are 55 years old or greater and have experienced cessation of menses for at least 1 year.)
  18. Have contraindication to estrogen and/or progestin therapy or allergy to the use of estradiol and/or progesterone or any components of the investigational drugs.
  19. Use 15 or more cigarettes per day or currently use any electronic cigarettes.
  20. Have a history of drug and/or alcohol abuse within one year of start of study.
  21. Have used, within 28 days prior to the initial dose of study medication at Visit 1, any medication known to induce or inhibit CYP3A4 enzyme activity that may affect estrogen and/or progestin drug metabolism. (See 48TUSection 4.3U48T)
  22. Have used, within 28 days prior to Screening, or plan to use during the study, any prescription or over-the-counter (OTC) medications (including herbal products, such as St. John's Wort) that would be expected to alter progesterone or estrogen activity or is being used to treat vasomotor symptoms. (See Section 4.3U48T)

  23. Have used estrogen alone or estrogen/progestin, SERM (selective estrogen receptor modulator), testosterone, or estrogen/testosterone for any of the following time periods:

      1. Vaginal nonsystemic hormonal products (rings, creams, gels) within 7 days prior to Screening, or vaginal systemic products (e.g., FemRing) within 28 days prior to Screening.
      2. Transdermal estrogen alone or estrogen/progestin products within 8 weeks prior to Screening.
      3. Oral estrogen and/or progestin and/or SERM therapy within 8 weeks prior to Screening.
      4. Progestational implants, estrogen or estrogen/progestational injectable drug therapy within 3 months prior to Screening.
      5. Estrogen pellet therapy or progestational injectable drug therapy within 6 months prior to Screening.
      6. Percutaneous estrogen lotions/gels within 8 weeks prior to Screening.
      7. Oral, topical, vaginal, patch, implantable or injectable androgen therapy within 8 weeks prior to Screening.
  24. Have used an intrauterine device (IUD) within the 12 weeks prior to Screening.
  25. For subjects in the VMS Substudy only: use of medication that may affect the outcome of the vasomotor symptom endpoints within 28 days prior to Screening (e.g. SSRIs [selective serotonin reuptake inhibitors], SNRIs [serotonin and norepinephrine reuptake inhibitors], aldomet, dopaminergic or antidopaminergic drugs, gabapentin, clonidine, or bellergal.)
  26. Have any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the subject from safely participating in the study or complying with protocol requirements.
  27. Have a Screening endometrial biopsy sample that is found by both primary pathologists to have endometrial tissue insufficient for diagnosis, no endometrium identified, or no tissue identified. (With the approval of the Medical Monitor, the Screening endometrial biopsy may be repeated once.)
  28. Endometrial polyps with atypical nuclei reported by at least 1 central pathologist.
  29. Have contraindication to any planned study assessments (e.g., endometrial biopsy).
  30. Have participated in another clinical trial within 30 days prior to Screening, have received an investigational drug within the three months prior to the initial dose of study medication, or be likely to participate in a clinical trial or receive another investigational medication during the study.
  31. Currently use marijuana.

Contacts and Locations

Locations

United States, Alabama

Simon Williamson Clinic

Birmingham, Alabama, United States, 35211

Medical Affiliated Research Center

Huntsville, Alabama, United States, 35801

Coastal Clinical Research

Mobile, Alabama, United States, 36608

Mobile Ob-Gyn, P.C.

Mobile, Alabama, United States, 36608

Montgomery Women's Health

Montgomery, Alabama, United States, 36117

United States, Arizona

Advanced Research Associates

Glendale, Arizona, United States, 85308

Cactus Clinical Research

Mesa, Arizona, United States, 85209

Precision Trials

Phoenix, Arizona, United States, 85032

Radiant Research (Tucson)

Tucson, Arizona, United States, 85712

Visions Clinical Research Tucson

Tucson, Arizona, United States, 85712

United States, Arkansas

Health Star Research, LLC

Hot Springs, Arkansas, United States, 71913

United States, California

Sutter East Bay Medical Foundation

Berkeley, California, United States, 94705

Grossmont Center for Clinical Research

La Mesa, California, United States, 91942

Futura Research

Norwalk, California, United States, 90650

Medical Center for Clinical Research

San Diego, California, United States, 92108

Women's Health Care Research Corp.

San Diego, California, United States, 92111

Radiant Research, Inc.

Santa Rosa, California, United States, 95405

Diablo Clinical Research

Walnut Creek, California, United States, 94598

United States, Colorado

Downtown Women's Healthcare

Denver, Colorado, United States, 80209

Horizon's Clinical Research Center

Denver, Colorado, United States, 80220

Red Rocks OB/Gyn

Lakewood, Colorado, United States, 80228

United States, Connecticut

Clinical Research Consulting

Milford, Connecticut, United States, 06460

Coastal Connecticut Research

New London, Connecticut, United States, 06320

United States, Florida

South Florida Medical Research

Aventura, Florida, United States, 33180

Nature Coast Clinical Research

Crystal River, Florida, United States, 34429

Clinical Physiology Associates

Fort Myers, Florida, United States, 33916

Southeastern Integrated Medical, PL, d/b/a Florida Medical Research

Gainesville, Florida, United States, 32607

UF College of Medicine-Jacksonville, Dept. of Obstetrics and Gynecology

Jacksonville, Florida, United States, 32207

Suncoast Research

Margate, Florida, United States, 33063

Accelovance

Melbourne, Florida, United States, 32934

Suncoast Clinical Research, Inc

New Port Richey, Florida, United States, 34652

Ideal Clinical Research

North Miami Beach, Florida, United States, 33162

Segal Institute

North Miami, Florida, United States, 33161

Compass Research

Orlando, Florida, United States, 32806

Radiant Research (St. Petersburg)

Pinellas Park, Florida, United States, 33781

All Women's Healthcare of West Broward Discovery Clinical Research

Plantation, Florida, United States, 33324

Comprehensive Clinical Trials

West Palm Beach, Florida, United States, 33409

United States, Georgia

Radiant Research (Atlanta)

Atlanta, Georgia, United States, 30328

Women's Health Associates

Atlanta, Georgia, United States, 30342

Soapstone Center for Clinical Research

Decatur, Georgia, United States, 30034

Wake Research - Mount Vernon Clinical Research

Sandy Springs, Georgia, United States, 30328

Fellows Research Alliance

Savannah, Georgia, United States, 31406

United States, Idaho

Elite Clinical Trials

Blackfoot, Idaho, United States, 83221

Advanced Clinical Research

Meridian, Idaho, United States, 83642

United States, Illinois

Biofortis

Addison, Illinois, United States, 60101

Women's Health Practice

Champaign, Illinois, United States, 61820

Radiant Research (Chicago)

Chicago, Illinois, United States, 60654

United States, Indiana

The South Bend Clinic Granger

Granger, Indiana, United States, 46530

Davis Clinic

Indianapolis, Indiana, United States, 46250

United States, Kansas

Cypress Medical Research Center, LLC

Wichita, Kansas, United States, 67226

United States, Kentucky

Central Kentucky Research Associates

Lexington, Kentucky, United States, 40509

Bluegrass Clinical Research

Louisville, Kentucky, United States, 40291

United States, Louisiana

Horizon Research Group

Eunice, Louisiana, United States, 70535

United States, Maryland

Maryland Center for Sexual Health

Lutherville, Maryland, United States, 21093

United States, Michigan

Quest Research Institute

Bingham Farms, Michigan, United States, 48025

Female Pelvic Medicine & Urogynecology

Grand Rapids, Michigan, United States, 49503

Beyer Research

Kalamazoo, Michigan, United States, 49009

Saginaw Valley Medical Research Group

Saginaw, Michigan, United States, 48604

United States, Missouri

Radiant Research (St. Louis)

Saint Louis, Missouri, United States, 63141

United States, Montana

Billings Clinical Research

Billings, Montana, United States, 59101

Montana Health

Billings, Montana, United States, 59102

United States, Nebraska

Women's Clinic of Lincoln

Lincoln, Nebraska, United States, 68510

United States, Nevada

Affiliated Clinical Research INC

Las Vegas, Nevada, United States, 89113

Affiliated Clinical Research

Las Vegas, Nevada, United States, 89128

United States, New Jersey

Lawrence OB-GYN Clinical Research

Lawrenceville, New Jersey, United States, 08648

United States, New Mexico

Albuquerque Clinical Trials, Inc.

Albuquerque, New Mexico, United States, 87102

Bosque Women's Care

Albuquerque, New Mexico, United States, 87109

Southwest Clinical Research

Albuquerque, New Mexico, United States, 87109

United States, New York

Columbia University

New York, New York, United States, 10032

Suffolk OB/GYN

Port Jefferson, New York, United States, 11777

Upstate Clinical Research Associates

Williamsville, New York, United States, 14221

United States, North Carolina

Women's Wellness Clinic

Durham, North Carolina, United States, 27713

Carolina Medical Trials

High Point, North Carolina, United States, 27262

Centre OBGYN

Raleigh, North Carolina, United States, 27607

Wake County Research

Raleigh, North Carolina, United States, 27612

Lyndhurst Clinical Research

Salem, North Carolina, United States, 27103

Carolina Medical Trials

Winston-Salem, North Carolina, United States, 27103

Hawthorne Research

Winston-Salem, North Carolina, United States, 27103

Triad Ob-Gyn

Winston-Salem, North Carolina, United States, 27103

United States, North Dakota

Lillestol Research

Fargo, North Dakota, United States, 58103

United States, Ohio

Radiant Research (Akron)

Akron, Ohio, United States, 44311

University of Cincinnati Physicians Company

Cincinnati, Ohio, United States, 45267-0457

Rapid Medical Research

Cleveland, Ohio, United States, 44122

Columbus Center for Women's Health Research

Columbus, Ohio, United States, 43213

HWC Women's Research Center

Englewood, Ohio, United States, 45322

United States, Oklahoma

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States, 73112

United States, Oregon

Sunstone Medical Research

Medford, Oregon, United States, 97504

United States, Pennsylvania

The Clinical Trial Center

Jenkintown, Pennsylvania, United States, 19046

Clinical Research of Philadelphia

Philadelphia, Pennsylvania, United States, 19114

Clinical Trials Research Services, LLC

Pittsburgh, Pennsylvania, United States, 15206

United States, Rhode Island

Omega Medical Research

Warwick, Rhode Island, United States, 02886

United States, South Carolina

Fellows Research Group

Bluffton, South Carolina, United States, 29910

Vista Clinical Research

Columbia, South Carolina, United States, 29201

Upstate Pharmaceutical Research

Greenville, South Carolina, United States, 29615

Coastal Carolina Research Center

Mount Pleasant, South Carolina, United States, 29464

United States, Tennessee

Chattanooga Medical Research

Chattanooga, Tennessee, United States, 37404

Volunteer Research Group/NOCCR

Knoxville, Tennessee, United States, 37920

United States, Texas

DiscoveResearch, Inc.

Bryan, Texas, United States, 77802

Advanced Research Associates

Corpus Christi, Texas, United States, 78414

Research Across America

Dallas, Texas, United States, 75234

Brownstone Clinical Trials

Fort Worth, Texas, United States, 76104

Advances in Health

Houston, Texas, United States, 77030

The Women's Hospital of Texas

Houston, Texas, United States, 77054

TMC Life Research

Houston, Texas, United States, 77054

Protenium Clinical Research

Hurst, Texas, United States, 76054

MacArthur OB/GYN

Irving, Texas, United States, 75062

Clinical Trials of Texas

San Antonio, Texas, United States, 78229

Stone Oak, LLC dba Discovery Clinical Trials

San Antonio, Texas, United States, 78258

NECRSA

Schertz, Texas, United States, 78154

United States, Utah

PRO/ Salt Lake Women's Center

Draper, Utah, United States, 84020

Wasatch Clinical Research, LLC

Salt Lake City, Utah, United States, 84107

Jean Brown Research

Salt Lake City, Utah, United States, 84124

United States, Virginia

UVA/Midlife Health at North Ridge

Charlottesville, Virginia, United States, 22908

Clinical Research Center Eastern Virginia Medical School

Norfolk, Virginia, United States, 23507

Virginia Women's Center

Richmond, Virginia, United States, 23233

National Clinical Research-Richmond, Inc

Richmond, Virginia, United States, 23294

Tidewater Clinical Research

Virginia Beach, Virginia, United States, 23456

United States, Washington

Seattle Women's Health Research, Gynecology

Seattle, Washington, United States, 98105

North Spokane Women's Health

Spokane, Washington, United States, 99027

Sponsors and Collaborators

TherapeuticsMD

Investigators

• Study Director: Sebastian Mirkin, MD; TherapeuticsMD

More Information

Publications:

Hilditch JR, Lewis J, Peter A, van Maris B, Ross A, Franssen E, Guyatt GH, Norton PG, Dunn E. A menopause-specific quality of life questionnaire: development and psychometric properties. Maturitas. 1996 Jul;24(3):161-75. doi: 10.1016/s0378-5122(96)82006-8. Erratum In: Maturitas 1996 Nov;25(3):231.

Gerlinger C, Gude K, Hiemeyer F, Schmelter T, Schafers M. An empirically validated responder definition for the reduction of moderate to severe hot flushes in postmenopausal women. Menopause. 2012 Jul;19(7):799-803. doi: 10.1097/gme.0b013e31823de8ba.

Spritzer, K. L. & Hays, R. D. (2003, November). MOS Sleep Scale: A Manual for Use and Scoring, Version 1.0. Los Angeles, CA.

Kurman RJ, Ellenson L H, and Ronnett B.M., ed. Blaustein's Pathology of the Female Genital Tract. 6th ed. New York, NY: Springer; 2011:305-452.

Revicki D, Hays RD, Cella D, Sloan J. Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol. 2008 Feb;61(2):102-9. doi: 10.1016/j.jclinepi.2007.03.012. Epub 2007 Aug 3.

Hays RD and Stewart AL. Sleep measures. In AL Stewart & JE Ware (eds), Measuring functioning and well-being: The Medical Outcomes Study approach (pp 235-259). Durham, NC: Duke University Press, 1992.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

McClung MR, Kagan R, Graham S, Bernick B, Mirkin S, Constantine G. Effects of E2/P4 oral capsules on bone turnover in women with vasomotor symptoms. Menopause. 2022 Feb 14;29(3):304-308. doi: 10.1097/GME.0000000000001915.

Constantine GD, Simon JA, Kaunitz AM, Pickar JH, Revicki DA, Graham S, Bernick B, Mirkin S. TX-001HR is associated with a clinically meaningful effect on severity of moderate to severe vasomotor symptoms in the REPLENISH trial. Menopause. 2020 Nov;27(11):1236-1241. doi: 10.1097/GME.0000000000001602.

Black DR, Minkin MJ, Graham S, Bernick B, Mirkin S. Effects of combined 17beta-estradiol and progesterone on weight and blood pressure in postmenopausal women of the REPLENISH trial. Menopause. 2020 Sep 14;28(1):32-39. doi: 10.1097/GME.0000000000001659.

Kaunitz AM, Bitner D, Constantine GD, Bernick B, Graham S, Mirkin S. 17beta-estradiol/progesterone in a single, oral, softgel capsule (TX-001HR) significantly increased the number of vasomotor symptom-free days in the REPLENISH trial. Menopause. 2020 Dec;27(12):1382-1387. doi: 10.1097/GME.0000000000001615.

Mirkin S, Goldstein SR, Archer DF, Pickar JH, Graham S, Bernick B. Endometrial safety and bleeding profile of a 17beta-estradiol/progesterone oral softgel capsule (TX-001HR). Menopause. 2020 Apr;27(4):410-417. doi: 10.1097/GME.0000000000001480.

Lobo RA, Kaunitz AM, Santoro N, Bernick B, Graham S, Mirkin S. Metabolic and cardiovascular effects of TX-001HR in menopausal women with vasomotor symptoms. Climacteric. 2019 Dec;22(6):610-616. doi: 10.1080/13697137.2019.1640197. Epub 2019 Jul 31.

Mirkin S, Graham S, Revicki DA, Bender RH, Bernick B, Constantine GD. Relationship between vasomotor symptom improvements and quality of life and sleep outcomes in menopausal women treated with oral, combined 17beta-estradiol/progesterone. Menopause. 2019 Jan 9;26(6):637-642. doi: 10.1097/GME.0000000000001294.

Kagan R, Constantine G, Kaunitz AM, Bernick B, Mirkin S. Improvement in sleep outcomes with a 17beta-estradiol-progesterone oral capsule (TX-001HR) for postmenopausal women. Menopause. 2018 Dec 21;26(6):622-628. doi: 10.1097/GME.0000000000001278.

Lobo RA, Archer DF, Kagan R, Kaunitz AM, Constantine GD, Pickar JH, Graham S, Bernick B, Mirkin S. A 17beta-Estradiol-Progesterone Oral Capsule for Vasomotor Symptoms in Postmenopausal Women: A Randomized Controlled Trial. Obstet Gynecol. 2018 Jul;132(1):161-170. doi: 10.1097/AOG.0000000000002645. Erratum In: Obstet Gynecol. 2018 Sep;132(3):786.

Mirkin S, Amadio JM, Bernick BA, Pickar JH, Archer DF. 17beta-Estradiol and natural progesterone for menopausal hormone therapy: REPLENISH phase 3 study design of a combination capsule and evidence review. Maturitas. 2015 May;81(1):28-35. doi: 10.1016/j.maturitas.2015.02.266. Epub 2015 Mar 9.

• Responsible Party: TherapeuticsMD
• ClinicalTrials.gov Identifier: NCT01942668
• Other Study ID Numbers: TXC12-05; REPLENISH Trial ( Other Identifier: Sponsor )
• First Posted: September 16, 2013
• Results First Posted: May 6, 2019
• Last Update Posted: May 6, 2019
• Last Verified: April 2019

Keywords provided by TherapeuticsMD:

Vasomotor symptoms; Hot flashes; Endometrial protection

Additional relevant MeSH terms:

Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate; Progesterone; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins