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

Endometrial Protection - Hyperplasia

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.

Time frame: Baseline and Month 12

Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

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.

Time frame: Baseline and Week 1

Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

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.

Time frame: Baseline and Week 2

Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

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.

Time frame: Baseline and Week 3

Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

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.

Time frame: Baseline and Week 4

Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

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.

Time frame: Baseline and Week 5

Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

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.

Time frame: Baseline and Week 6

Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

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.

Time frame: Baseline and Week 7

Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

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.

Time frame: Baseline and Week 8

Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

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.

Time frame: Baseline and Week 9

Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

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.

Time frame: Baseline and Week 10

Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

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.

Time frame: Baseline and Week 11

Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

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.

Time frame: Baseline and Week 12

Severity of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

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).

Time frame: Baseline and Week 1

Severity of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

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).

Time frame: Baseline and Week 2

Severity of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

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).

Time frame: Baseline and Week 3

Severity of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

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).

Time frame: Baseline and Week 4

Severity of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

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).

Time frame: Baseline and Week 5

Severity of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

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).

Time frame: Baseline and Week 6

Severity of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

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).

Time frame: Baseline and Week 7

Severity of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

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).

Time frame: Baseline and Week 8

Severity of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

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).

Time frame: Baseline and Week 9

Severity of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

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).

Time frame: Baseline and Week 10

Severity of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

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).

Time frame: Baseline and Week 11

Severity of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

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).

Time frame: Baseline and Week 12

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

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.

Time frame: Baseline and Week 1

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

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.

Time frame: Baseline and Week 2

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

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.

Time frame: Baseline and Week 3

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

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.

Time frame: Baseline and Week 4

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

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.

Time frame: Baseline and Week 5

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

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.

Time frame: Baseline and Week 6

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

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.

Time frame: Baseline and Week 7

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

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.

Time frame: Baseline and Week 8

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

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.

Time frame: Baseline and Week 9

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

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.

Time frame: Baseline and Week 10

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

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.

Time frame: Baseline and Week 11

Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

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.

Time frame: Baseline and Week 12

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

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).

Time frame: Baseline and Week 1

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

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).

Time frame: Baseline and Week 2

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

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).

Time frame: Baseline and Week 3

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

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).

Time frame: Baseline and Week 4

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

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).

Time frame: Baseline and Week 5

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

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).

Time frame: Baseline and Week 6

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

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).

Time frame: Baseline and Week 7

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

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).

Time frame: Baseline and Week 8

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

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).

Time frame: Baseline and Week 9

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

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).

Time frame: Baseline and Week 10

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

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).

Time frame: Baseline and Week 11

Severity of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

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).

Time frame: Baseline and Week 12

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 1 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe VMS from Baseline to Week 1.

Time frame: Baseline and Week 1

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 2 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 2.

Time frame: Baseline and Week 2

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 3 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 3.

Time frame: Baseline and Week 3

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 4 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 4.

Time frame: Baseline and Week 4

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 5 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 5.

Time frame: Baseline and Week 5

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 6 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 6.

Time frame: Baseline and Week 6

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 7 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 7.

Time frame: Baseline and Week 7

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 8 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 8.

Time frame: Baseline and Week 8

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 9 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 9.

Time frame: Baseline and Week 9

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 10 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 10.

Time frame: Baseline and Week 10

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 11 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 11.

Time frame: Baseline and Week 11

Reduction of Frequency of Moderate to Severe Vasomotor Symptoms - Week 12 (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of moderate to severe vasomotor symptoms from Baseline to Week 12.

Time frame: Baseline and Week 12

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 1 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 1.

Time frame: Baseline and Week 1

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 2 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 2.

Time frame: Baseline and Week 2

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 3 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 3.

Time frame: Baseline and Week 3

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 4 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 4.

Time frame: Baseline and Week 4

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 5 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 5.

Time frame: Baseline and Week 5

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 6 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 6.

Time frame: Baseline and Week 6

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 7 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 7.

Time frame: Baseline and Week 7

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 8 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 8.

Time frame: Baseline and Week 8

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 9 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 9.

Time frame: Baseline and Week 9

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 10 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 10.

Time frame: Baseline and Week 10

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 11 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 11.

Time frame: Baseline and Week 11

Reduction of Frequency of Mild, Moderate and Severe Vasomotor Symptoms - Week 12 - (MITT-VMS)

Number of Subjects with \>=50%, and separately, \>=75% reduction in frequency of mild, moderate and severe vasomotor symptoms from Baseline to Week 12.

Time frame: Baseline and Week 12

Clinical Global Impression (CGI) - Week 4 (MITT-VMS)

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.

Time frame: Baseline and Week 4

Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 4 (MITT-VMS)

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.

Time frame: Baseline and Week 4

Clinical Global Impression (CGI) - Week 8 (MITT-VMS)

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.

Time frame: Baseline and Week 8

Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 8 (MITT-VMS)

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.

Time frame: Baseline and Week 8

Clinical Global Impression (CGI) - Week 12 (MITT-VMS)

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.

Time frame: Baseline and Week 12

Mean Change in Frequency of Moderate to Severe VMS for the Respective CGI Category - Week 12 (MITT-VMS)

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.

Time frame: Baseline and Week 12

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 1 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 2 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 3 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 4 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 5 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 6 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 7 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 8 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 9 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 10 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 11 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: Cycle 12 to 13

Number of Subjects Without Bleeding for Consecutive Cycles

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.

Time frame: The 13th Cycle

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 1 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 2 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 3 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 4 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 5 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 6 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 7 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 8 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 9 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 10 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 11 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: Cycle 12 to 13

Number of Subjects With Cumulative Amenorrhea From 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.

Time frame: The 13th Cycle

Subject Incidence With Spotting - Trimester 1 (Safety Pop.)

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.

Time frame: Trimester 1

Subject Incidence With Spotting - Trimester 2 (Safety Pop.)

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.

Time frame: Trimester 2

Subject Incidence With Spotting - Trimester 3 (Safety Pop.)

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.

Time frame: Trimester 3

Subject Incidence With Spotting - Trimester 4 (Safety Pop.)

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.

Time frame: Trimester 4

Number of Days With Spotting - Trimester 1 (Safety Pop.)

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.

Time frame: Trimester 1

Number of Days With Spotting - Trimester 2 (Safety Pop.)

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.

Time frame: Trimester 2

Number of Days With Spotting - Trimester 3 (Safety Pop.)

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.

Time frame: Trimester 3

Number of Days With Spotting - Trimester 4 (Safety Pop.)

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.

Time frame: Trimester 4

Subject Incidence With Bleeding - Trimester 1 (Safety Pop.)

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.

Time frame: Trimester 1

Subject Incidence With Bleeding - Trimester 2 (Safety Pop.)

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.

Time frame: Trimester 2

Subject Incidence With Bleeding - Trimester 3 (Safety Pop.)

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.

Time frame: Trimester 3

Subject Incidence With Bleeding - Trimester 4 (Safety Pop.)

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.

Time frame: Trimester 4

Number of Days With Bleeding - Trimester 1 (Safety Pop.)

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.

Time frame: Trimester 1

Number of Days With Bleeding - Trimester 2 (Safety Pop.)

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.

Time frame: Trimester 2

Number of Days With Bleeding - Trimester 3 (Safety Pop.)

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.

Time frame: Trimester 3

Number of Days With Bleeding - Trimester 4 (Safety Pop.)

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.

Time frame: Trimester 4

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT-VMS)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT-VMS)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT-VMS)

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".

Time frame: Baseline and Month 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT-VMS)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT-VMS)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT-VMS)

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".

Time frame: Baseline and Month 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT-VMS)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT-VMS)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT-VMS)

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".

Time frame: Baseline and Month 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT-VMS)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT-VMS)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT-VMS)

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".

Time frame: Baseline and Month 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT-VMS)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT-VMS)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT-VMS)

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".

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT-VMS)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT-VMS)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT-VMS)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 (MITT-VMS)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT-VMS)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT-VMS)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT-VMS)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT-VMS)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT-VMS)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT-VMS)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT-VMS)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT-VMS)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT-VMS)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT-VMS)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT-VMS)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT-VMS)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT-VMS)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT-VMS)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT-VMS)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT-VMS)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT-VMS)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT-VMS)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 6 - (MITT-VMS)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT-VMS)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT-VMS)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT-VMS)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT-VMS)

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.

Time frame: Baseline and Month 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Week 12 (MITT)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 6 (MITT)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Vasomotor Domain Score - Month 12 (MITT)

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".

Time frame: Baseline and Month 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Week 12 (MITT)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 6 (MITT)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Psychosocial Domain Score - Month 12 (MITT)

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".

Time frame: Baseline and Month 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Week 12 (MITT)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 6 (MITT)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Physical Domain Score - Month 12 (MITT)

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".

Time frame: Baseline and Month 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Week 12 (MITT)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 6 (MITT)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Sexual Domain Score - Month 12 (MITT)

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".

Time frame: Baseline and Month 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Week 12 (MITT)

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".

Time frame: Baseline and Week 12

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 6 (MITT)

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".

Time frame: Baseline and Month 6

Menopause-specific Quality of Life Questionnaire (MENQOL) - Overall Scores - Month 12 (MITT)

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".

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Week 12 (MITT)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 6 (MITT)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Sleep Scale - Total Sleep Score - Month 12 (MITT)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Week 12 - (MITT)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 6 - (MITT)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Disturbance - Month 12 - (MITT)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Week 12 - (MITT)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 6 - (MITT)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Snoring - Month 12 - (MITT)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Week 12 - (MITT)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 6 - (MITT)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Short of Breath or Headache - Month 12 - (MITT)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Week 12 - (MITT)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 6 - (MITT)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Adequacy - Month 12 - (MITT)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Week 12 - (MITT)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 6 - (MITT)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Somnolence - Month 12 - (MITT)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Week 12 - (MITT)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 6 - (MITT)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index I - Month 12 - (MITT)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Week 12 - (MITT)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Sleep Problems Index II - Month 6 - (MITT)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Individual Score for Sleep Problems Index II - Month 12 - (MITT)

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.

Time frame: Baseline and Month 12

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Week 12 - (MITT)

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.

Time frame: Baseline and Week 12

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 6 - (MITT)

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.

Time frame: Baseline and Month 6

Medical Outcomes Sleep Study (MOS) Optimal Sleep - Month 12 - (MITT)

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.

Time frame: Baseline and Month 12