Trial Outcomes & Findings for Treatment Of Hot Flashes/Flushes In Postmenopausal Women (WARM Study) (NCT NCT00604825)

NCT ID: NCT00604825

Last Updated: 2017-10-03

Results Overview

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. The severity of AEs was assessed by the investigator as mild, moderate or severe.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 356 participants
• Primary outcome timeframe: Up to 21 weeks
• Results posted on: 2017-10-03

Participant Flow

The study was conducted from at 75 centers (2 in Spain, 3 each in Argentina, New Zealand and the United Kingdom, 4 in Italy, 5 in Australia, 6 in Sweden, 12 in Germany, and 37 in the United States) from 17-July-2007 to 23-July-2008.

A total of 982 healthy postmenopausal participants with moderate to extremely severe vasomotor symptoms were screened (626 screen failures) and 356 were randomized.

Participant milestones

Measure	Placebo Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg Eligible participants received GSK232802 25 milligram (mg) tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Overall Study STARTED	90	87	89	90
Overall Study COMPLETED	81	72	73	79
Overall Study NOT COMPLETED	9	15	16	11

Reasons for withdrawal

Measure	Placebo Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg Eligible participants received GSK232802 25 milligram (mg) tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Overall Study Adverse Event	2	6	7	4
Overall Study Lost to Follow-up	0	3	1	0
Overall Study Protocol Violation	0	1	0	0
Overall Study Withdrawal by Subject	4	3	5	5
Overall Study Lack of Efficacy	3	2	1	0
Overall Study Did not meet eligibility criteria	0	0	2	0
Overall Study Physician Decision	0	0	0	1
Overall Study Exclusion criterion met	0	0	0	1

Baseline Characteristics

Treatment Of Hot Flashes/Flushes In Postmenopausal Women (WARM Study)

Baseline characteristics by cohort

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	Total n=356 Participants Total of all reporting groups
Age, Continuous	55.2 Years STANDARD_DEVIATION 4.17 • n=5 Participants	54.9 Years STANDARD_DEVIATION 4.72 • n=7 Participants	54.2 Years STANDARD_DEVIATION 4.78 • n=5 Participants	54.0 Years STANDARD_DEVIATION 5.18 • n=4 Participants	54.6 Years STANDARD_DEVIATION 4.73 • n=21 Participants
Sex: Female, Male Female	90 Participants n=5 Participants	87 Participants n=7 Participants	89 Participants n=5 Participants	90 Participants n=4 Participants	356 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	31 Participants n=21 Participants
Race (NIH/OMB) White	84 Participants n=5 Participants	78 Participants n=7 Participants	79 Participants n=5 Participants	79 Participants n=4 Participants	320 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 21 weeks

Population: Safety Population which comprised of all randomized participants who received at least one dose of investigational product.

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. The severity of AEs was assessed by the investigator as mild, moderate or severe.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=88 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE AE	54 Participants	52 Participants	45 Participants	51 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE SAE	2 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE Mild AE	19 Participants	20 Participants	8 Participants	18 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE Moderate AE	30 Participants	25 Participants	32 Participants	23 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) and Number of Participants With Mild, Moderate and Severe AE Severe AE	5 Participants	7 Participants	4 Participants	10 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

SBP and DBP were measured after the participant had rested for at least 5 minutes in a sitting or supine position. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in SBP and DBP at Week 12 are presented.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=88 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 SBP	2.6 Millimeters of mercury Standard Deviation 15.26	1.8 Millimeters of mercury Standard Deviation 12.19	-1.6 Millimeters of mercury Standard Deviation 11.04	-0.4 Millimeters of mercury Standard Deviation 12.61
Change From Baseline in Vital Signs of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 12 DBP	0.1 Millimeters of mercury Standard Deviation 8.38	1.0 Millimeters of mercury Standard Deviation 9.28	0.7 Millimeters of mercury Standard Deviation 7.04	-0.1 Millimeters of mercury Standard Deviation 9.06

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Heart rate was measured after the participant had rested for at least 5 minutes in a sitting or supine position. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in heart rate at Week 12 are presented.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Vital Sign of Heart Rate at Week 12	-0.2 Beats per minute Standard Deviation 9.84	0.6 Beats per minute Standard Deviation 8.27	2.8 Beats per minute Standard Deviation 8.09	0.3 Beats per minute Standard Deviation 9.66

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Serum hormone markers included TSH. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in TSH at Week 12 are presented.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=78 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Thyroid Stimulating Hormone (TSH) at Week 12	0.236 Milliunits/Liter Standard Deviation 0.8942	0.034 Milliunits/Liter Standard Deviation 0.9951	0.397 Milliunits/Liter Standard Deviation 1.3453	0.238 Milliunits/Liter Standard Deviation 0.9280

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Serum hormone markers included T4 and additional pharmacodynamics marker included insulin. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in T4 and insulin at Week 12 are presented.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=88 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Thyroxine (T4) and Insulin at Week 12 T4	-0.190 Picomole per Liter Standard Deviation 1.8660	-0.350 Picomole per Liter Standard Deviation 1.6473	-0.582 Picomole per Liter Standard Deviation 1.6272	-0.425 Picomole per Liter Standard Deviation 1.8863
Change From Baseline in Thyroxine (T4) and Insulin at Week 12 Insulin	12.747 Picomole per Liter Standard Deviation 83.3643	4.563 Picomole per Liter Standard Deviation 49.2320	3.205 Picomole per Liter Standard Deviation 44.1258	-19.297 Picomole per Liter Standard Deviation 137.5697

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Fasting lipids included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholestereol direct and triglycerides. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline in fasting lipid profile at Week 12 are presented.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=88 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Fasting Lipid Profile at Week 12 Cholesterol	0.055 Millimole per Liter Standard Deviation 0.7977	0.019 Millimole per Liter Standard Deviation 0.5600	-0.203 Millimole per Liter Standard Deviation 0.5985	-0.062 Millimole per Liter Standard Deviation 0.7300
Change From Baseline in Fasting Lipid Profile at Week 12 HDL cholestereol, direct	0.047 Millimole per Liter Standard Deviation 0.1851	0.093 Millimole per Liter Standard Deviation 0.2296	0.070 Millimole per Liter Standard Deviation 0.2184	0.069 Millimole per Liter Standard Deviation 0.2357
Change From Baseline in Fasting Lipid Profile at Week 12 LDL cholesterol	0.030 Millimole per Liter Standard Deviation 0.6987	-0.221 Millimole per Liter Standard Deviation 0.4564	-0.430 Millimole per Liter Standard Deviation 0.5290	0.208 Millimole per Liter Standard Deviation 0.6744
Change From Baseline in Fasting Lipid Profile at Week 12 Triglycerides	-0.060 Millimole per Liter Standard Deviation 0.7480	0.309 Millimole per Liter Standard Deviation 0.4718	0.370 Millimole per Liter Standard Deviation 0.6892	0.166 Millimole per Liter Standard Deviation 0.4941

PRIMARY outcome

Timeframe: Baseline (Week 0) to Week 12

Population: Uterine Safety Population which comprised of all randomized participants who had a uterus and also received at least one dose of investigational product. Only those participants available at the specified time points were analyzed.

All participants with an intact uterus participating in this study underwent a TVUS at Baseline and at Week 12, to investigate the cause of any abnormal uterine bleeding during the study. In the event the TVUS was not well visualized or there were abnormal findings at either visit, or the bi-layer thickness exceeded 5 millimeter at Week 12, a SIS was conducted to visualize the anterior and posterior walls. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline and Week 12 in heart rate are presented.

Outcome measures

Measure	Placebo n=54 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=53 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=52 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=51 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) TVUS Bi-layer Endometrial Thickness	-0.07 Millimeter Standard Deviation 1.255	0.13 Millimeter Standard Deviation 1.383	0.79 Millimeter Standard Deviation 1.895	1.12 Millimeter Standard Deviation 2.051
Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) SIS Posterior Endometrial Thickness	8.40 Millimeter Standard Deviation NA Single participant	0.90 Millimeter Standard Deviation NA Single participant	—	—
Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) SIS Anterior Endometrial Thickness	-1.20 Millimeter Standard Deviation NA Single participant	1.70 Millimeter Standard Deviation NA Single participant	—	—
Change From Baseline in Bi-layer Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) or Saline Infusion Sonohysterography (SIS) SIS Total Endometrial Thickness	7.20 Millimeter Standard Deviation NA Single participant	2.60 Millimeter Standard Deviation NA Single participant	—	—

PRIMARY outcome

Timeframe: Baseline (Week 0) to Week 12

Population: Uterine safety Population. Only those participants available at the specified time points were analyzed.

Endometrial biopsies were conducted at Baseline and end-of-treatment (end-of-treatment values were defined as the last available post-Baseline values before treatment was stopped) for all study participants with an intact uterus. These procedures were performed by an experienced physician. Each biopsy was obtained after the TVUS was performed. Proliferative endometrium also meant hyperplasia without atypia (normal).

Outcome measures

Measure	Placebo n=54 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=53 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=52 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=51 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Endometrial Biopsy Pathology Baseline · Normal	29 Participants	33 Participants	34 Participants	31 Participants
Endometrial Biopsy Pathology Baseline · No tissue/insufficient tissue	23 Participants	19 Participants	17 Participants	20 Participants
Endometrial Biopsy Pathology Baseline · Proliferative endometrium	1 Participants	0 Participants	1 Participants	0 Participants
Endometrial Biopsy Pathology Baseline · Progestational endometrium	0 Participants	1 Participants	0 Participants	0 Participants
Endometrial Biopsy Pathology Baseline · Polyp	0 Participants	0 Participants	0 Participants	0 Participants
Endometrial Biopsy Pathology End of treatment · Normal	19 Participants	27 Participants	24 Participants	31 Participants
Endometrial Biopsy Pathology End of treatment · No tissue/insufficient tissue	23 Participants	19 Participants	16 Participants	9 Participants
Endometrial Biopsy Pathology End of treatment · Proliferative endometrium	0 Participants	1 Participants	0 Participants	3 Participants
Endometrial Biopsy Pathology End of treatment · Progestational endometrium	0 Participants	0 Participants	0 Participants	1 Participants
Endometrial Biopsy Pathology End of treatment · Polyp	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Follow-up (Day 112)

Population: Uterine Safety Population. Only those participants available at the specified time points were analyzed.

After completion of the 12-week treatment period, participants with an intact uterus received a 14-day cycle of progestogen (10 mg medroxyprogesterone acetate [MPA]) to induce withdrawal bleeding. All participants were required to return to clinic for Follow-Up Visit. Participants were asked to record occurrence of bleeding/spotting each day, from the day MPA dosing began until Follow-up using the following criteria: None (no bleeding or spotting), Spotting: any vaginal flow requiring not more than one sanitary napkin or tampon per day (lightly stained and not soaked through) and Bleeding: any vaginal flow requiring more than one sanitary napkin or tampon per day. The following information was recorded in electronic case report form: start and stop date of MPA administration as well as dates of any spotting/bleeding. Duration of spotting or bleeding is presented.

Outcome measures

Measure	Placebo n=48 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=48 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=42 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=47 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Occurrence of Withdrawal Bleeding-duration of Spotting/Bleeding	0.0 Days Interval 0.0 to 23.0	0.0 Days Interval 0.0 to 36.0	0.0 Days Interval 0.0 to 45.0	1.0 Days Interval 0.0 to 30.0

PRIMARY outcome

Timeframe: Up to Follow-up (Day 112)

Population: Uterine Safety Population. Only those participants available at the specified time points were analyzed.

After completion of the 12-week treatment period, participants with an intact uterus received a 14-day cycle of progestogen (10 mg MPA) to induce withdrawal bleeding. All participants were required to return to clinic for Follow-Up Visit. Participants were asked to record occurrence of bleeding/spotting each day, from the day MPA dosing began until Follow-up using the following criteria: None (no bleeding or spotting), Spotting: any vaginal flow requiring not more than one sanitary napkin or tampon per day (lightly stained and not soaked through) and Bleeding: any vaginal flow requiring more than one sanitary napkin or tampon per day. The following information was recorded in electronic case report form: start and stop date of MPA administration as well as dates of any spotting/bleeding. Duration of spotting, bleeding and also spotting/bleeding combined is presented.

Outcome measures

Measure	Placebo n=48 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=48 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=42 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=47 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined Number of days of spotting	0.0 Days Interval 0.0 to 12.0	0.0 Days Interval 0.0 to 9.0	0.0 Days Interval 0.0 to 10.0	0.0 Days Interval 0.0 to 16.0
Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined Number of days of bleeding	0.0 Days Interval 0.0 to 5.0	0.0 Days Interval 0.0 to 4.0	0.0 Days Interval 0.0 to 5.0	0.0 Days Interval 0.0 to 17.0
Occurrence of Withdrawal Bleeding-number of Days of Spotting, Number of Days of Bleeding, Number of Days of Spotting/Bleeding Combined Number of days of spotting/bleeding combined	0.0 Days Interval 0.0 to 14.0	0.0 Days Interval 0.0 to 11.0	0.0 Days Interval 0.0 to 13.0	1.0 Days Interval 0.0 to 20.0

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Intent-to-Treat Population (ITT) Population which comprised of all randomized participants. Last Observation Carried Forward (LOCF) was the imputation technique used.

Individual VMS (hot flash or night sweats) events were recorded by participants in an electronic diary (eDiary) using as Global Change Question. The frequency was assessed using the question 1 as "Since you started the study medication, how has the number of your hot flashes (including night sweats) changed?". the response was rated on a 7-point scale from +3 to -3, where +3=A great deal better, +2=Moderately better, +1=A little better, 0=No change, -1=A little worse, -2=Moderately worse and -3=A great deal worse. The score ranged from +3 to -3, where +3 implied absence of symptoms and lower score implied more severe symptoms. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Adjusted mean is presented as least square mean.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Mean Change in Frequency of Vasomotor Symptoms (VMS) From Baseline at Week 12	-5.53 Scores on a Scale Standard Error 0.466	-4.78 Scores on a Scale Standard Error 0.522	-4.31 Scores on a Scale Standard Error 0.500	-7.59 Scores on a Scale Standard Error 0.479

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.

Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change questions. VMS severity was as follows: mild=score of 1 (brief wave of heat with minimal discomfort, usually without perspiration; able to continue activity [or sleep]), moderate=score of 2(heat with some discomfort, usually with perspiration; minimal interruption of activity [or sleep]), severe=score of 3(intense heat with considerable discomfort, usually with heavy sweating; may be unable to resume activity [or sleep] right away) and extremely severe=score of 4 (unbearable heat with intense discomfort, usually with pouring sweat; may be unable to resume activity [or sleep] for quite a while). Total score ranged from 1 to 4 and is the sum of severity scores divided by total number of VMS events. Higher score indicates worst condition. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Mean Change in Severity of VMS From Baseline at Week 12	-0.37 Scores on a Scale Standard Error 0.093	-0.21 Scores on a Scale Standard Error 0.104	-0.05 Scores on a Scale Standard Error 0.099	-0.89 Scores on a Scale Standard Error 0.095

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Thrombotic marker included fibrinogen. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=70 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=65 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=67 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=75 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Thrombotic Marker- Fibrinogen at Week 12	-0.081 Gram per LIter Standard Deviation 0.5889	-0.246 Gram per LIter Standard Deviation 0.8377	-0.293 Gram per LIter Standard Deviation 0.6487	-0.198 Gram per LIter Standard Deviation 0.5291

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Thrombotic marker included tPA antigen. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=79 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=70 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=70 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=75 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Thrombotic Marker- Tissue Plasminogen Activator (tPA) Antigen at Week 12	0.200 Microgram per Liter Standard Deviation 3.0996	-0.139 Microgram per Liter Standard Deviation 2.2818	-1.224 Microgram per Liter Standard Deviation 2.8039	0.115 Microgram per Liter Standard Deviation 2.4548

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Inflammatory marker included hs-CRP. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=78 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=69 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=72 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline and Week 12 in Inflammatory Marker- High Sensitivity C-reactive Protein (Hs-CRP) at Week 12	0.008 Milligram per Liter Standard Deviation 1.5780	2.181 Milligram per Liter Standard Deviation 9.4203	0.833 Milligram per Liter Standard Deviation 2.3385	0.557 Milligram per Liter Standard Deviation 3.6617

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Inflammatory marker included Endothelin-1. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=76 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=67 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=71 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=73 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline and Week 12 in Inflammatory Marker- Endothelin-1 at Week 12	-1.204 Nanogram per Liter Standard Deviation 1.4544	-0.897 Nanogram per Liter Standard Deviation 1.3425	-1.087 Nanogram per Liter Standard Deviation 1.5720	-0.945 Nanogram per Liter Standard Deviation 1.6884

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Hematology parameter included hematocrit. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=80 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=71 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=72 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=76 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline and Week 12 in Hematology Parameter- Hematocrit at Week 12	-0.003 Fraction Standard Deviation 0.0303	-0.006 Fraction Standard Deviation 0.0192	-0.019 Fraction Standard Deviation 0.0313	-0.002 Fraction Standard Deviation 0.0198

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Hematology parameter included MCH. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=80 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=71 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=72 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=76 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Hematology Parameter- Mean Corpuscle Hemoglobin (MCH) at Week 12	-0.260 Picograms Standard Deviation 0.6118	-0.221 Picograms Standard Deviation 0.6094	-0.207 Picograms Standard Deviation 0.6878	-0.326 Picograms Standard Deviation 0.6005

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Hematology parameter included MCV. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=80 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=71 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=72 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=76 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Hematology Parameter- Mean Corpuscle Volume (MCV) at Week 12	-0.813 Femtoliters Standard Deviation 1.8356	-0.169 Femtoliters Standard Deviation 2.1179	-0.694 Femtoliters Standard Deviation 2.2558	-0.368 Femtoliters Standard Deviation 1.7802

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Hematology parameter included RBC count. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=80 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=71 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=72 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=76 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Hematology Parameter- Red Blood Cell (RBC) Count at Week 12	0.005 Trillion cells per Liter Standard Deviation 0.3073	-0.059 Trillion cells per Liter Standard Deviation 0.1833	-0.179 Trillion cells per Liter Standard Deviation 0.3053	-0.005 Trillion cells per Liter Standard Deviation 0.2103

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Hematology parameters included Hemoglobin and MCHC. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=80 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=71 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=72 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=76 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 Hemoglobin	-1.275 Gram per Liter Standard Deviation 8.9216	-2.887 Gram per Liter Standard Deviation 5.6050	-5.944 Gram per Liter Standard Deviation 8.3293	-1.382 Gram per Liter Standard Deviation 6.3476
Change From Baseline in Hematology Parameters- Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at Week 12 MCHC	-0.275 Gram per Liter Standard Deviation 8.2768	-2.000 Gram per Liter Standard Deviation 9.0885	0.500 Gram per Liter Standard Deviation 11.1381	-2.079 Gram per Liter Standard Deviation 8.0957

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Hematology parameters included basophils, eosinophils, lymphocytes, monocytes, platelet count, segmented neutrophils, total neutrophils and WBC count. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline and Week 12 in basophils, eosinophils, lymphocytes, monocytes, platelet count, segmented neutrophils, total neutrophils and WBC count are presented.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=88 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils and White Blood Cell (WBC) Count at Week 12 Basophils	-0.000 Gigacells per Liter Standard Deviation 0.0186	0.000 Gigacells per Liter Standard Deviation 0.0186	0.002 Gigacells per Liter Standard Deviation 0.0185	-0.002 Gigacells per Liter Standard Deviation 0.0192
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils and White Blood Cell (WBC) Count at Week 12 Eosinophils	-0.000 Gigacells per Liter Standard Deviation 0.0686	-0.008 Gigacells per Liter Standard Deviation 0.0789	0.004 Gigacells per Liter Standard Deviation 0.1070	-0.005 Gigacells per Liter Standard Deviation 0.0788
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils and White Blood Cell (WBC) Count at Week 12 Lymphocytes	0.025 Gigacells per Liter Standard Deviation 0.4305	0.121 Gigacells per Liter Standard Deviation 0.3786	0.020 Gigacells per Liter Standard Deviation 0.3901	0.013 Gigacells per Liter Standard Deviation 0.3742
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils and White Blood Cell (WBC) Count at Week 12 Monocytes	0.021 Gigacells per Liter Standard Deviation 0.0903	-0.008 Gigacells per Liter Standard Deviation 0.1224	0.007 Gigacells per Liter Standard Deviation 0.1033	-0.007 Gigacells per Liter Standard Deviation 0.1340
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils and White Blood Cell (WBC) Count at Week 12 Platelet count	-4.463 Gigacells per Liter Standard Deviation 28.6153	-8.507 Gigacells per Liter Standard Deviation 28.6061	-7.127 Gigacells per Liter Standard Deviation 33.4873	-1.316 Gigacells per Liter Standard Deviation 53.4174
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils and White Blood Cell (WBC) Count at Week 12 Segmented neutrophils	-0.126 Gigacells per Liter Standard Deviation 0.8908	0.160 Gigacells per Liter Standard Deviation 0.9377	-0.076 Gigacells per Liter Standard Deviation 1.0209	0.044 Gigacells per Liter Standard Deviation 0.8687
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils and White Blood Cell (WBC) Count at Week 12 Total neutrophils	-0.127 Gigacells per Liter Standard Deviation 0.8909	0.160 Gigacells per Liter Standard Deviation 0.9377	-0.076 Gigacells per Liter Standard Deviation 1.0209	0.043 Gigacells per Liter Standard Deviation 0.8686
Change From Baseline in Hematology Parameters- Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils and White Blood Cell (WBC) Count at Week 12 WBC count	-0.078 Gigacells per Liter Standard Deviation 1.1316	0.265 Gigacells per Liter Standard Deviation 1.0780	-0.043 Gigacells per Liter Standard Deviation 1.1956	0.042 Gigacells per Liter Standard Deviation 0.9380

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included albumin and total protein. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=88 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 Albumin	-0.333 Gram per Liter Standard Deviation 2.3979	-1.194 Gram per Liter Standard Deviation 1.9183	-1.743 Gram per Liter Standard Deviation 2.1775	-0.810 Gram per Liter Standard Deviation 2.3484
Change From Baseline in Clinical Chemistry Parameters- Albumin and Total Protein at Week 12 Total Protein	-0.519 Gram per Liter Standard Deviation 3.6301	-0.306 Gram per Liter Standard Deviation 3.1248	-0.892 Gram per Liter Standard Deviation 3.5791	-0.506 Gram per Liter Standard Deviation 3.6755

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included creatinine, direct bilirubin, total bilirubin and uric acid. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 Creatinine	-1.765 Micromoles per Liter Standard Deviation 5.5052	0.847 Micromoles per Liter Standard Deviation 8.3795	0.811 Micromoles per Liter Standard Deviation 6.6676	-0.506 Micromoles per Liter Standard Deviation 7.1052
Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 Direct bilirubin	-0.037 Micromoles per Liter Standard Deviation 0.7817	-0.097 Micromoles per Liter Standard Deviation 0.7152	-0.122 Micromoles per Liter Standard Deviation 0.8432	-0.076 Micromoles per Liter Standard Deviation 0.8129
Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 Total bilirubin	-0.556 Micromoles per Liter Standard Deviation 3.0083	-0.667 Micromoles per Liter Standard Deviation 3.9611	-1.324 Micromoles per Liter Standard Deviation 2.8579	-0.646 Micromoles per Liter Standard Deviation 3.0215
Change From Baseline in Clinical Chemistry Parameters- Creatinine, Direct Bilirubin, Total Bilirubin and Uric Acid at Week 12 Uric acid	1.395 Micromoles per Liter Standard Deviation 41.3998	0.278 Micromoles per Liter Standard Deviation 42.8302	11.324 Micromoles per Liter Standard Deviation 40.0196	1.532 Micromoles per Liter Standard Deviation 37.4983

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included ALT, ALP and AST. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 ALT	0.160 Units per Liter Standard Deviation 6.8838	-2.681 Units per Liter Standard Deviation 10.3200	-1.986 Units per Liter Standard Deviation 8.8943	-2.291 Units per Liter Standard Deviation 6.9746
Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 ALP	-0.037 Units per Liter Standard Deviation 10.0629	-6.403 Units per Liter Standard Deviation 9.8577	-8.878 Units per Liter Standard Deviation 13.2520	-1.962 Units per Liter Standard Deviation 11.0598
Change From Baseline in Clinical Chemistry Parameters- Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at Week 12 AST	-0.247 Units per Liter Standard Deviation 5.2190	-1.139 Units per Liter Standard Deviation 7.3356	-0.743 Units per Liter Standard Deviation 6.7643	-1.228 Units per Liter Standard Deviation 4.8831

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included calcium, C02 content, chloride, phosphorous, inorganic, potassium, sodium and urea. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 Calcium	-0.009 Millimol per Liter Standard Deviation 0.0730	-0.039 Millimol per Liter Standard Deviation 0.0987	-0.050 Millimol per Liter Standard Deviation 0.0815	-0.051 Millimol per Liter Standard Deviation 0.0813
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 C02 content/bicarbonate	0.728 Millimol per Liter Standard Deviation 2.9284	0.014 Millimol per Liter Standard Deviation 2.2611	-0.486 Millimol per Liter Standard Deviation 2.6651	-0.506 Millimol per Liter Standard Deviation 2.9651
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 Chloride	0.012 Millimol per Liter Standard Deviation 2.0946	0.389 Millimol per Liter Standard Deviation 2.3887	0.189 Millimol per Liter Standard Deviation 2.1433	0.304 Millimol per Liter Standard Deviation 2.1204
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 Phosphorous-inorganic	0.007 Millimol per Liter Standard Deviation 0.2167	-0.046 Millimol per Liter Standard Deviation 0.1525	-0.029 Millimol per Liter Standard Deviation 0.3494	-0.060 Millimol per Liter Standard Deviation 0.1538
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 Potassium	-0.049 Millimol per Liter Standard Deviation 0.2916	-0.038 Millimol per Liter Standard Deviation 0.4061	0.004 Millimol per Liter Standard Deviation 0.3134	-0.035 Millimol per Liter Standard Deviation 0.3955
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 Sodium	-0.420 Millimol per Liter Standard Deviation 1.8899	0.139 Millimol per Liter Standard Deviation 2.0849	-0.608 Millimol per Liter Standard Deviation 1.7736	-0.076 Millimol per Liter Standard Deviation 1.7743
Change From Baseline in Clinical Chemistry Parameters- Calcium, Carbon Dioxide (C02) Content, Chloride, Phosphorous, Inorganic, Potassium, Sodium and Urea at Week 12 Urea	0.102 Millimol per Liter Standard Deviation 1.2350	0.160 Millimol per Liter Standard Deviation 1.3445	0.385 Millimol per Liter Standard Deviation 1.1448	-0.097 Millimol per Liter Standard Deviation 1.3095

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 8

Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.

Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using as Global Change Question. The frequency was assessed using the question 1 as "Since you started the study medication, how has the number of your hot flashes (including night sweats) changed?". the response was rated on a 7-point scale from +3 to -3, where +3=A great deal better, +2=Moderately better, +1=A little better, 0=No change, -1=A little worse, -2=Moderately worse and -3=A great deal worse. The score ranged from +3 to -3, where +3 implied absence of symptoms and lower score implied more severe symptoms. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 Week 4	-4.20 Scores on a Scale Standard Error 0.435	-3.95 Scores on a Scale Standard Error 0.487	-4.27 Scores on a Scale Standard Error 0.469	-5.68 Scores on a Scale Standard Error 0.447
Mean Change in Frequency of VMS From Baseline to Weeks 4 and 8 Week 8	-5.00 Scores on a Scale Standard Error 0.446	-4.09 Scores on a Scale Standard Error 0.500	-4.07 Scores on a Scale Standard Error 0.479	-7.24 Scores on a Scale Standard Error 0.459

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 8

Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.

Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change questions. The VMS severity was as follows: mild=score of 1 (brief wave of heat with minimal discomfort, usually without perspiration; able to continue activity [or sleep]), moderate=score of 2(heat with some discomfort, usually with perspiration; minimal interruption of activity [or sleep]), severe=score of 3(intense heat with considerable discomfort, usually with heavy sweating; may be unable to resume activity [or sleep] right away) and extremely severe=score of 4 (unbearable heat with intense discomfort, usually with pouring sweat; may be unable to resume activity [or sleep] for quite a while). Total score ranged from 1 to 4 and is the sum of severity scores divided by total number of VMS events. Higher score indicates worst condition. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 Week 4	-0.39 Scores on a Scale Standard Error 0.072	-0.22 Scores on a Scale Standard Error 0.079	-0.22 Scores on a Scale Standard Error 0.076	-0.62 Scores on a Scale Standard Error 0.073
Mean Change in Severity of VMS From Baseline to Weeks 4 and 8 Week 8	-0.32 Scores on a Scale Standard Error 0.081	-0.11 Scores on a Scale Standard Error 0.091	-0.14 Scores on a Scale Standard Error 0.086	-0.77 Scores on a Scale Standard Error 0.083

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.

Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change question. The severity of VMS events were calculated using self-reported participants assessments recorded and transmitted by eDiary. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Percent change was calculated by multiplying the change from baseline value with 100. Number of participants with VMS percent change from Baseline responders with a reduction in frequency at Week 12 of at least 50%, at least 75%, and 100% are presented.

Outcome measures

Measure	Placebo n=88 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=75 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=81 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=84 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Number of Participants With VMS Percent Change From Baseline Responders With a Reduction in Frequency at Week 12 of at Least 50%, at Least 75%, and 100% At least 50% reduction in frequency	43 Participants	36 Participants	32 Participants	61 Participants
Number of Participants With VMS Percent Change From Baseline Responders With a Reduction in Frequency at Week 12 of at Least 50%, at Least 75%, and 100% At least 75% reduction in frequency	21 Participants	16 Participants	15 Participants	42 Participants
Number of Participants With VMS Percent Change From Baseline Responders With a Reduction in Frequency at Week 12 of at Least 50%, at Least 75%, and 100% At least 100% reduction in frequency	3 Participants	1 Participants	0 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT Population with LOCF analysis. Only those participants available at the specified time points were analyzed.

Individual VMS (hot flash or night sweats) events were recorded by participants in an eDiary using global change questions. The VMS severity was as follows: mild (brief wave of heat with minimal discomfort, usually without perspiration; able to continue activity [or sleep]), moderate (heat with some discomfort, usually with perspiration; minimal interruption of activity [or sleep]), severe (intense heat with considerable discomfort, usually with heavy sweating; may be unable to resume activity [or sleep] right away) and extremely severe (unbearable heat with intense discomfort, usually with pouring sweat; may be unable to resume activity [or sleep] for quite a while). The severity of VMS events were calculated using self-reported participants assessments recorded and transmitted by eDiary. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Percent change was calculated by multiplying change from Baseline value with 100.

Outcome measures

Measure	Placebo n=88 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=75 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=81 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=84 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Number of Participants With VMS Percent Change From Baseline Responders With a Reduction in Severity at Week 12 of at Least 50%, at Least 75%, and 100% At least 50% reduction in severity	8 Participants	7 Participants	3 Participants	28 Participants
Number of Participants With VMS Percent Change From Baseline Responders With a Reduction in Severity at Week 12 of at Least 50%, at Least 75%, and 100% At least 75% reduction in severity	3 Participants	1 Participants	0 Participants	10 Participants
Number of Participants With VMS Percent Change From Baseline Responders With a Reduction in Severity at Week 12 of at Least 50%, at Least 75%, and 100% At least 100% reduction in severity	3 Participants	1 Participants	0 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

MENQOL instrument is a 32-item, validated questionnaire designed to measure symptoms that participants experience due to menopause and degree to which these symptoms bother them. Each item references a symptom and is composed of two-part question; a yes/no confirmation that the participant has symptom followed by a question asking how bothersome the symptom is, if present. The MENQOL items are designed to be grouped into domains that address vasomotor (items 1-3), psychosocial(items 4-10), physical (items 11-26, 30-32) and sexual symptoms (items 27-29). Each domain is given a separate score; there is no overall score. The domain score is sum of individual item scores divided by number of items in that domain. Since domain subscales are not comprised of an equivalent number of items, mean of subscale is used as overall subscale score. Each domain score ranges from 1 to 8. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Vasomotor Domain Score; Week 4	-1.36 Scores on a Scale Standard Error 0.205	-1.26 Scores on a Scale Standard Error 0.227	-1.27 Scores on a Scale Standard Error 0.213	-2.13 Scores on a Scale Standard Error 0.207
Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Psychosocial Domain Score; Week 4	-0.51 Scores on a Scale Standard Error 0.157	-0.46 Scores on a Scale Standard Error 0.173	-0.42 Scores on a Scale Standard Error 0.165	-0.63 Scores on a Scale Standard Error 0.161
Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Physical Domain Score; Week 4	-0.65 Scores on a Scale Standard Error 0.122	-0.50 Scores on a Scale Standard Error 0.135	-0.58 Scores on a Scale Standard Error 0.127	-0.70 Scores on a Scale Standard Error 0.123
Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sexual Domain Score; Week 4	-0.62 Scores on a Scale Standard Error 0.187	-0.62 Scores on a Scale Standard Error 0.203	-0.62 Scores on a Scale Standard Error 0.200	-0.85 Scores on a Scale Standard Error 0.188
Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Vasomotor Domain Score; Week 12	-1.79 Scores on a Scale Standard Error 0.241	-1.21 Scores on a Scale Standard Error 0.260	-1.09 Scores on a Scale Standard Error 0.253	-2.99 Scores on a Scale Standard Error 0.237
Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Psychosocial Domain Score; Week 12	-0.46 Scores on a Scale Standard Error 0.178	-0.45 Scores on a Scale Standard Error 0.193	-0.33 Scores on a Scale Standard Error 0.189	-0.91 Scores on a Scale Standard Error 0.174
Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Physical Domain Score; Week 12	-0.59 Scores on a Scale Standard Error 0.133	-0.36 Scores on a Scale Standard Error 0.144	-0.50 Scores on a Scale Standard Error 0.139	-0.87 Scores on a Scale Standard Error 0.129
Change in Menopause Quality of Life (MENQoL) Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sexual Domain Score; Week 12	-0.47 Scores on a Scale Standard Error 0.194	-0.18 Scores on a Scale Standard Error 0.214	-0.52 Scores on a Scale Standard Error 0.215	-1.04 Scores on a Scale Standard Error 0.194

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The MOS Sleep Scale is a validated questionnaire designed to measure a participant sleep quality via 12 questions. Items are designed to be grouped into domains that include sleep disturbance (items 1, 3, 7, 8), sleep adequacy (items 4, 12), daytime somnolence (items 6, 9, 11), sleep quantity (2), 6-Item Sleep Scale (items 4, 5, 7, 8, 9, 12) and 9-Item Sleep Scale (items 3, 4, 5, 6, 7, 8, 9, 11, 12). Each domain is given a separate score. The domain score is calculated as the sum of the individual item scores in that domain. Transformed scores were calculated for the domains only. This transformation converts the raw domain score to a 0 to 100 scale following the formula: Transformed score = ([Raw score - Lowest possible score]/Possible score range)*100. Lowest score 0 indicates best sleep quality and higher score 100 indicates worst sleep quality. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sleep Disturbance domain; Week 4	1.62 Scores on a Scale Standard Error 0.378	1.29 Scores on a Scale Standard Error 0.422	1.05 Scores on a Scale Standard Error 0.400	1.68 Scores on a Scale Standard Error 0.386
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sleep Adequacy domain; Week 4	0.57 Scores on a Scale Standard Error 0.294	0.66 Scores on a Scale Standard Error 0.329	0.37 Scores on a Scale Standard Error 0.311	1.00 Scores on a Scale Standard Error 0.300
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sleep Somnolence domain; Week 4	0.43 Scores on a Scale Standard Error 0.297	-0.19 Scores on a Scale Standard Error 0.332	0.00 Scores on a Scale Standard Error 0.314	0.65 Scores on a Scale Standard Error 0.303
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sleep Quantity domain; Week 4	0.24 Scores on a Scale Standard Error 0.121	0.21 Scores on a Scale Standard Error 0.134	0.13 Scores on a Scale Standard Error 0.127	0.47 Scores on a Scale Standard Error 0.124
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) 6-Item Sleep Scale domain; Week 4	2.19 Scores on a Scale Standard Error 0.560	1.85 Scores on a Scale Standard Error 0.621	1.53 Scores on a Scale Standard Error 0.588	2.87 Scores on a Scale Standard Error 0.568
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) 9-Item Sleep Scale domain; Week 4	3.01 Scores on a Scale Standard Error 0.774	2.26 Scores on a Scale Standard Error 0.858	2.01 Scores on a Scale Standard Error 0.813	4.05 Scores on a Scale Standard Error 0.784
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed Sleep Disturbance domain; Week 4	6.76 Scores on a Scale Standard Error 1.577	5.35 Scores on a Scale Standard Error 1.758	4.37 Scores on a Scale Standard Error 1.667	7.01 Scores on a Scale Standard Error 1.607
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed Sleep Adequacy domain; Week 4	4.75 Scores on a Scale Standard Error 2.450	5.48 Scores on a Scale Standard Error 2.738	3.10 Scores on a Scale Standard Error 2.594	8.35 Scores on a Scale Standard Error 2.501
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed Sleep Somnolence domain; Week 4	2.38 Scores on a Scale Standard Error 1.651	-1.03 Scores on a Scale Standard Error 1.842	0.02 Scores on a Scale Standard Error 1.747	3.62 Scores on a Scale Standard Error 1.685
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed 6-Item Sleep Scale domain; Week 4	6.08 Scores on a Scale Standard Error 1.556	5.15 Scores on a Scale Standard Error 1.724	4.25 Scores on a Scale Standard Error 1.634	7.98 Scores on a Scale Standard Error 1.577
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed 9-Item Sleep Scale domain; Week 4	5.57 Scores on a Scale Standard Error 1.434	4.19 Scores on a Scale Standard Error 1.588	3.73 Scores on a Scale Standard Error 1.506	7.50 Scores on a Scale Standard Error 1.453
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sleep Disturbance domain; Week 12	1.34 Scores on a Scale Standard Error 0.366	1.37 Scores on a Scale Standard Error 0.397	0.82 Scores on a Scale Standard Error 0.390	2.12 Scores on a Scale Standard Error 0.364
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sleep Adequacy domain; Week 12	1.36 Scores on a Scale Standard Error 0.302	0.79 Scores on a Scale Standard Error 0.328	0.02 Scores on a Scale Standard Error 0.322	1.36 Scores on a Scale Standard Error 0.301
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sleep Somnolence domain; Week 12	0.07 Scores on a Scale Standard Error 0.295	0.41 Scores on a Scale Standard Error 0.321	0.13 Scores on a Scale Standard Error 0.315	1.17 Scores on a Scale Standard Error 0.294
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Sleep Quantity domain; Week 12	0.22 Scores on a Scale Standard Error 0.131	0.23 Scores on a Scale Standard Error 0.142	-0.08 Scores on a Scale Standard Error 0.142	0.46 Scores on a Scale Standard Error 0.133
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) 6-Item Sleep Scale domain; Week 12	2.62 Scores on a Scale Standard Error 0.571	2.19 Scores on a Scale Standard Error 0.616	0.57 Scores on a Scale Standard Error 0.604	3.68 Scores on a Scale Standard Error 0.565
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) 9-Item Sleep Scale domain; Week 12	2.87 Scores on a Scale Standard Error 0.774	3.17 Scores on a Scale Standard Error 0.834	1.36 Scores on a Scale Standard Error 0.818	5.32 Scores on a Scale Standard Error 0.765
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed Sleep Disturbance domain; Week 12	5.57 Scores on a Scale Standard Error 1.525	5.70 Scores on a Scale Standard Error 1.654	3.41 Scores on a Scale Standard Error 1.627	8.85 Scores on a Scale Standard Error 1.518
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed Sleep Adequacy domain; Week 12	11.35 Scores on a Scale Standard Error 2.514	6.62 Scores on a Scale Standard Error 2.734	0.19 Scores on a Scale Standard Error 2.682	11.30 Scores on a Scale Standard Error 2.508
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed Sleep Somnolence domain; Week 12	0.41 Scores on a Scale Standard Error 1.639	2.30 Scores on a Scale Standard Error 1.781	0.72 Scores on a Scale Standard Error 1.749	6.48 Scores on a Scale Standard Error 1.635
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed 6-Item Sleep Scale domain; Week 12	7.27 Scores on a Scale Standard Error 1.586	6.08 Scores on a Scale Standard Error 1.711	1.57 Scores on a Scale Standard Error 1.678	10.23 Scores on a Scale Standard Error 1.570
Change in Medical Outcomes Study (MOS) Sleep Score From Baseline to Visits 6 (Week 4) and Visit 8 (Week 12) Transformed 9-Item Sleep Scale domain; Week 12	5.32 Scores on a Scale Standard Error 1.433	5.88 Scores on a Scale Standard Error 1.544	2.51 Scores on a Scale Standard Error 1.515	9.85 Scores on a Scale Standard Error 1.417

SECONDARY outcome

Timeframe: Baseline (Week 0) to Visit 8 (Week 12)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The VVA Symptoms Scale questionnaire is an 18-item instrument that captures symptoms related to VVA, asks participant to identify symptom that bothers them the most and contains items to assess degree of bother participants experience from each symptom and impact that most bothersome symptom has on their daily life. Items 1 to 8 had responses and scores of none=0, mild=1, moderate=2 and severe=3. Items 9 to 18 had responses and scores of not at all=0, a little=1, moderately=2 and a lot=3. Severity item and bothersome item respectively were as follows: vaginal dryness:1 and 9; Vaginal itching:2 and 10; Vaginal irritation:3 and 11; Painful urination:4 and 12; Difficulty urinating:5 and 13; Vaginal pain associated with sexual activity:6 and 14; Vaginal bleeding associated with sexual activity:7 and 15. Total score ranged from 0 to 3; higher score indicated most bothersome. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Severity of vaginal dryness	-0.2 Scores on a Scale Standard Deviation 0.79	-0.1 Scores on a Scale Standard Deviation 0.81	-0.3 Scores on a Scale Standard Deviation 0.86	-0.4 Scores on a Scale Standard Deviation 1.03
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Severity of vaginal itching	0.0 Scores on a Scale Standard Deviation 0.75	0.1 Scores on a Scale Standard Deviation 0.65	-0.2 Scores on a Scale Standard Deviation 0.74	0.0 Scores on a Scale Standard Deviation 0.58
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Severity of vaginal irritation	0.0 Scores on a Scale Standard Deviation 0.65	0.0 Scores on a Scale Standard Deviation 0.50	-0.1 Scores on a Scale Standard Deviation 0.74	0.0 Scores on a Scale Standard Deviation 0.67
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Severity of painful urination	0.0 Scores on a Scale Standard Deviation 0.43	0.0 Scores on a Scale Standard Deviation 0.36	0.0 Scores on a Scale Standard Deviation 0.48	-0.1 Scores on a Scale Standard Deviation 0.64
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Severity of urinating difficulty	0.0 Scores on a Scale Standard Deviation 0.19	0.0 Scores on a Scale Standard Deviation 0.43	-0.1 Scores on a Scale Standard Deviation 0.36	0.0 Scores on a Scale Standard Deviation 0.50
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Severity of vaginal pain due to sexual activity	-0.1 Scores on a Scale Standard Deviation 0.75	0.0 Scores on a Scale Standard Deviation 0.78	-0.1 Scores on a Scale Standard Deviation 0.93	-0.4 Scores on a Scale Standard Deviation 0.98
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Vaginal bleeding severity due to sexual activity	0.0 Scores on a Scale Standard Deviation 0.00	0.0 Scores on a Scale Standard Deviation 0.35	0.0 Scores on a Scale Standard Deviation 0.36	0.0 Scores on a Scale Standard Deviation 0.15
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Bothered by vaginal dryness	-0.1 Scores on a Scale Standard Deviation 0.79	-0.1 Scores on a Scale Standard Deviation 0.83	-0.3 Scores on a Scale Standard Deviation 0.89	-0.3 Scores on a Scale Standard Deviation 1.04
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Bothered by vaginal itching	-0.1 Scores on a Scale Standard Deviation 0.69	0.0 Scores on a Scale Standard Deviation 0.58	-0.3 Scores on a Scale Standard Deviation 0.72	0.1 Scores on a Scale Standard Deviation 0.69
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Bothered by vaginal irritation	-0.1 Scores on a Scale Standard Deviation 0.74	-0.1 Scores on a Scale Standard Deviation 0.66	-0.2 Scores on a Scale Standard Deviation 0.77	-0.1 Scores on a Scale Standard Deviation 0.63
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Bothered by painful urination	-0.1 Scores on a Scale Standard Deviation 0.48	0.1 Scores on a Scale Standard Deviation 0.46	-0.1 Scores on a Scale Standard Deviation 0.69	-0.1 Scores on a Scale Standard Deviation 0.52
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Bothered by difficulty in urination	-0.1 Scores on a Scale Standard Deviation 0.34	0.1 Scores on a Scale Standard Deviation 0.40	-0.1 Scores on a Scale Standard Deviation 0.51	0.0 Scores on a Scale Standard Deviation 0.46
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Bothered by vaginal pain due to sexual activity	-0.2 Scores on a Scale Standard Deviation 0.84	-0.1 Scores on a Scale Standard Deviation 0.70	0.0 Scores on a Scale Standard Deviation 0.96	-0.3 Scores on a Scale Standard Deviation 0.95
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Vaginal bleeding due to sexual activity bothering	0.0 Scores on a Scale Standard Deviation 0.00	0.0 Scores on a Scale Standard Deviation 0.41	-0.1 Scores on a Scale Standard Deviation 0.58	0.0 Scores on a Scale Standard Deviation 0.13
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Vaginal symptoms interference with sexual activity	-0.1 Scores on a Scale Standard Deviation 0.85	-0.1 Scores on a Scale Standard Deviation 0.86	-0.2 Scores on a Scale Standard Deviation 1.10	-0.6 Scores on a Scale Standard Deviation 1.15
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Vaginal symptoms interference with social activity	0.0 Scores on a Scale Standard Deviation 0.69	-0.1 Scores on a Scale Standard Deviation 0.62	-0.1 Scores on a Scale Standard Deviation 0.88	-0.2 Scores on a Scale Standard Deviation 0.72
Changes in Vulvar Vaginal Atrophy (VVA) Symptom Score From Baseline to Visit 8 (Week 12) Vaginal symptoms interference with daily activity	-0.1 Scores on a Scale Standard Deviation 0.80	0.0 Scores on a Scale Standard Deviation 0.50	-0.2 Scores on a Scale Standard Deviation 0.64	-0.2 Scores on a Scale Standard Deviation 0.57

SECONDARY outcome

Timeframe: Visit 2 (Day -21) to Visit 7 (Week 8)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The BFI is a validated questionnaire designed to measure a participant's fatigue via nine questions that are summated to create a total score. Items 1-3 request a rating on a scale ranging from 0 - 10 with 0 representing 'No Fatigue' and 10 representing 'As bad as you can imagine'. Five items 4A-4F request an interference score on a scale ranging from 0 - 10 with 0 representing 'Does not interfere' and 10 representing 'Completely Interferes'. The values of the scales for all items was used in scoring the response to each item. The following groupings of items was used to create domain scores. The total score is calculated by taking the sum of all 9 rating scales for a minimum score of 0 and a maximum score of 90. Higher score indicates more severe fatigue. Visit 2 was Day -21. Change from Visit 2 was calculated by subtracting Visit 2 values from post-Visit 2 values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 Total Score	-0.84 Scores on a Scale Standard Error 0.251	-0.43 Scores on a Scale Standard Error 0.279	-0.33 Scores on a Scale Standard Error 0.270	-0.40 Scores on a Scale Standard Error 0.260
Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 Severity domain	-0.87 Scores on a Scale Standard Error 0.289	-0.58 Scores on a Scale Standard Error 0.323	-0.53 Scores on a Scale Standard Error 0.314	-0.43 Scores on a Scale Standard Error 0.301
Change in Brief Fatigue Inventory (BFI) Score From Visit 2 to Visit 7 Interference domain	-0.82 Scores on a Scale Standard Error 0.261	-0.33 Scores on a Scale Standard Error 0.290	-0.25 Scores on a Scale Standard Error 0.281	-0.38 Scores on a Scale Standard Error 0.271

SECONDARY outcome

Timeframe: Visit 2 (Day -21) to Visit 7 (Week 8)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The CES-D is a questionnaire designed to measure depressive symptoms via 20 items that are summed to create a total score. Depressive symptoms are fairly common in postmenopausal women, and it's possible that stimulation of estrogen receptors via a selective estrogen receptor modulator may improve depressive symptoms. Questions 4, 8, 12 and 16 are weighted negatively (the scores are flipped prior to creating total score). If 3 or more items are missing then total score is missing. If fewer than 3 items are missing then missing item is set to group mean of that item for appropriate randomized treatment group. These means are only calculated if more than half of the participants used for calculation have responded to item. The items are summed to give total score ranging from 0 to 60. Lower score 0=no depression, higher score 60=higher degree of depression severity. Visit 2 was Day -21. Change from Visit 2 was calculated by subtracting Visit 2 values from post-Visit 2 values.

Outcome measures

Measure	Placebo n=78 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=70 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=77 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change in the Centers for Epidemiologic Studies in Depression (CES-D) Score From Visit 2 to Visit 7	-2.55 Scores on a Scale Standard Error 1.077	-1.26 Scores on a Scale Standard Error 1.172	-0.38 Scores on a Scale Standard Error 1.132	-1.27 Scores on a Scale Standard Error 1.090

SECONDARY outcome

Timeframe: Visit 2 (Day -21) to Visit 7 (Week 8)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

The WPAI is a questionnaire that measured workplace productivity and absenteeism via 6 items/questions, adapted to participants experiencing menopausal symptoms. Item 1 asks about current employment with a yes/no response. Items 2- 4 ask for continuous response in hours. Item 5 asks for response on rating scale related to WP ranging from 0:Menopausal symptoms had no effect on work to 10:Couldn't work at all. Item 6 asks for response on rating scale related to daily activities ranging from 0:no effect on daily activities to 10:Couldn't perform any daily activities. The score calculation- Effect on work: (Item 5 score÷10); Absenteeism: (Item 2÷Item 2+Item 4); Overall work impairment ([Item 2÷Item 2+Item 4]+ [1- {Item 2÷Item 2+Item 4}]*[ Item 5 score÷10]); Activity impairment: (Item 6 score÷10). Total score range from 0 to 10 where higher score indicates worst condition. Visit 2 was Day -21. Change from Visit 2 was calculated by subtracting Visit 2 values from post-Visit 2 values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=89 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 Effect on work	-16.80 Scores on a Scale Standard Error 3.319	-11.71 Scores on a Scale Standard Error 3.681	-6.43 Scores on a Scale Standard Error 3.199	-17.69 Scores on a Scale Standard Error 3.437
Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 Absenteeism	-1.10 Scores on a Scale Standard Error 1.229	-2.01 Scores on a Scale Standard Error 1.409	-2.67 Scores on a Scale Standard Error 1.224	-0.51 Scores on a Scale Standard Error 1.211
Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 Overall work impairment	-19.37 Scores on a Scale Standard Error 3.761	-17.82 Scores on a Scale Standard Error 4.318	-13.30 Scores on a Scale Standard Error 3.768	-18.48 Scores on a Scale Standard Error 3.763
Change in Work Productivity and Activity Impairment (WPAI) Score From Visit 2 to Visit 7 Activity impairment	-20.21 Scores on a Scale Standard Error 2.823	-13.50 Scores on a Scale Standard Error 3.082	-7.57 Scores on a Scale Standard Error 2.972	-18.58 Scores on a Scale Standard Error 2.886

SECONDARY outcome

Timeframe: Visit 2 (Day -21) to Visit 8 (Week 12)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Vaginal pH was measured at Visit 2 and Visit 8 using standard pH indicator strips available at the participating site clinic. The pH indicator strip was inserted to the upper portion of the proximal one third of the vaginal vault, placed in contact with the lateral vaginal mucosal wall for approximately 1 minute, and evaluated according to the instructions provided in the package labeling. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the vagina and higher the number, more alkaline the vagina with 7 being neutral. Change from Visit 2 to Visit 8 was calculated by subtracting Visit 2 values from Visit 8 values.

Outcome measures

Measure	Placebo n=80 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=74 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=75 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=84 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Visit 2 to Visit 8 in Vaginal pH	-0.13 Points on a scale Standard Error 0.137	-0.03 Points on a scale Standard Error 0.151	-0.09 Points on a scale Standard Error 0.146	-0.59 Points on a scale Standard Error 0.138

SECONDARY outcome

Timeframe: Visit 2 (Day -21) to Visit 8 (Week 12)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

A lateral vaginal wall specimen was collected at Visit 2 (Day -21) and Visit 8 (Week 12) and was sent to Central Pathology for analysis. Parabasal, intermediate, and superficial squamous cells were counted and percentages calculated. The VMI (also referred to as Maturation Value [MV]) of the vaginal mucosa was calculated according to the following equation:

VMI (MV)= (% Intermediate Cells x 0.5) + (% Superficial cells). Visit 2 was Day -21 and Visit 8 was Week 12. Change from Visit 2 to Visit 8 was calculated by subtracting Visit 2 values from Visit 8 values.

Outcome measures

Measure	Placebo n=68 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=61 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=64 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=69 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Visit 2 to Visit 8 in Percentage of Superficial Cells to Determine the Vaginal Maturation Index (VMI)	-1.0 Percentage of cells Standard Error 1.99	-0.3 Percentage of cells Standard Error 2.16	9.2 Percentage of cells Standard Error 2.11	13.5 Percentage of cells Standard Error 2.05

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Pharmacodynamic marker included glucose. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline in Glucose at Week 12	0.119 Millimoles per Liter Standard Deviation 0.7004	0.078 Millimoles per Liter Standard Deviation 0.6010	-0.072 Millimoles per Liter Standard Deviation 0.7097	-0.110 Millimoles per Liter Standard Deviation 0.6488

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Serum hormone included Estradiol. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline at Week 12 in estradiol are presented.

Outcome measures

Measure	Placebo n=80 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=71 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=72 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=77 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline at Week 12 in Serum Hormone Levels- Estradiol	-1.775 Picomoles per Liter Standard Deviation 88.9767	2.324 Picomoles per Liter Standard Deviation 71.5970	-8.403 Picomoles per Liter Standard Deviation 120.9173	178.312 Picomoles per Liter Standard Deviation 618.0547

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Serum hormones included FSH and LH. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=90 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=88 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) FSH	0.359 International units per Liter Standard Deviation 12.4050	-5.322 International units per Liter Standard Deviation 15.3625	-7.999 International units per Liter Standard Deviation 17.5791	-18.401 International units per Liter Standard Deviation 18.6976
Change From Baseline at Week 12 in Serum Hormone Levels- Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) LH	-1.454 International units per Liter Standard Deviation 9.7558	-1.571 International units per Liter Standard Deviation 8.6063	-3.362 International units per Liter Standard Deviation 9.4806	-1.732 International units per Liter Standard Deviation 13.2826

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Safety Population. Only those participants available at the specified time points were analyzed.

Serum hormones included testosterone. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values. Mean change from Baseline at Week 12 in testosterone are presented.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline at Week 12 in Serum Hormone Levels- Testosterone	-0.086 Nanomol per Liter Standard Deviation 0.5454	0.115 Nanomol per Liter Standard Deviation 0.5598	0.105 Nanomol per Liter Standard Deviation 0.4587	-0.009 Nanomol per Liter Standard Deviation 0.4252

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

To measure waist circumference, clothing was lifted from around the waist to ensure correct positioning of the measuring tape. Participants were instructed to stand erect with abdomen relaxed, arms at side, feet together, and weight equally divided over both legs. The non-stretchable tape was placed at the waist midway between the palpated iliac crest and the palpated lowest rib margin in the left and right mid-axillary lines. The tape was even, parallel to the floor not twisted with the measurement scale facing outward. The assessor was instructed to ensure that the tape was just touching the skin but not compressing the soft tissue. The measurement was made at the end of a normal expiration. The waist was measured at least twice or more if necessary, until two measurements were within 1 centimeter and the confirmatory reading recorded to one decimal place. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline at Week 12 in Waist Circumference	-0.83 Centimeters Standard Error 0.651	-1.29 Centimeters Standard Error 0.728	1.03 Centimeters Standard Error 0.709	0.12 Centimeters Standard Error 0.680

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

For hip circumference, the participant was instructed to stand erect with arms at sides and feet together. The measurement was taken at the point yielding the maximum circumference over the buttocks (widest part of the greater trochanters) with nonstretchable tape. The tape was even, not twisted with the measurement scale facing outward. The assessor was instructed to ensure that the tape was just touching the skin but not compressing the soft tissue. The hip should be measured at least twice until two measurements are within 1 centimeter and the last reading recorded. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=73 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline at Week 12 in Hip Circumference	-0.72 Centimeters Standard Error 0.596	0.13 Centimeters Standard Error 0.666	0.89 Centimeters Standard Error 0.650	0.14 Centimeters Standard Error 0.621

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Participants were weighed on a calibrated balance beam or digital scale. Participants were instructed to be dressed in light indoor clothing without shoes and also to have empty pockets and to void before weighing. It was strongly recommended that participants were weighed in the morning at the beginning of the clinic visit. Weight was measured at least twice or more if necessary, until two measurements were within 0.5 kilograms. The last (confirmed) reading was recorded in the electronic case report form. Weight was recorded in kilograms to the nearest tenth. When the weight was measured in pounds, it was converted into kilograms using the conversion factor: pounds/ 2.2 = kilograms. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline at Week 12 in Weight	0.13 Kilograms Standard Error 0.224	0.38 Kilograms Standard Error 0.250	0.36 Kilograms Standard Error 0.243	0.64 Kilograms Standard Error 0.234

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

BMI was calculated from height (taken at Screening Visit 1 [Day -35]) and weight at Week 12 using the formula: BMI = [weight in kilograms divided by (height in meters)^2]. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=81 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=72 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=74 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=79 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline at Week 12 in Body Mass Index (BMI)	0.05 Kilogram per square meters Standard Error 0.085	0.15 Kilogram per square meters Standard Error 0.095	0.12 Kilogram per square meters Standard Error 0.092	0.25 Kilogram per square meters Standard Error 0.088

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Body Composition Population which comprised of any ITT participants who provided consent for the body composition sub-study and received additional body composition assessments. Only those participants available at the specified time points were analyzed.

Thigh circumference was measured on the left leg directly below the gluteal fold; with the participant standing with both arms at the side, feet together, and with equal weight on both feet when this measurement was taken. The thigh was measured at least twice until two measurements were within 1 centimeter, and the last reading recorded. Abdomen body circumference and abdomen saggital diameter was measured in centimeter to once decimal place by Computerized tomography (CT) scan with the participant in supine position. CT scan of the abdomen was conducted at the Lumbar 4 vertebrae level. Scans were performed with 120 kilovolts, 5 millimeter slice thickness and 48 centimeter scan field of view. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=4 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=5 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=3 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=3 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference Abdomen body circumference	-1.20 Centimeters Standard Deviation 2.963	-0.30 Centimeters Standard Deviation 1.739	2.07 Centimeters Standard Deviation 3.066	-1.90 Centimeters Standard Deviation 2.884
Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference Abdomen saggital circumference	-0.50 Centimeters Standard Deviation 1.236	-0.04 Centimeters Standard Deviation 0.841	0.17 Centimeters Standard Deviation 0.379	-0.77 Centimeters Standard Deviation 1.002
Change From Baseline at Week 12 in Abdomen Body Circumference, Abdomen Saggital Diameter and Thigh Circumference Thigh circumference	0.13 Centimeters Standard Deviation 0.150	0.00 Centimeters Standard Deviation 0.797	0.23 Centimeters Standard Deviation 0.961	-0.07 Centimeters Standard Deviation 2.250

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Body Composition Population. Only those participants available at the specified time points were analyzed.

AVAT, ASAT, TSAT and TIAT was measured in centimeter to once decimal place by CT scan. A CT scan of the abdomen was conducted at the Lumbar 4 vertebrae level. A CT scan of the right thigh was performed at half the distance between the knee joint and greater trochanter femoralis. Scans were performed with 120 kilovolts, 5 millimeter slice thickness (thigh scan 3 millimeter slice thickness) and 48 centimeter scan field of view. Baseline was Week 0. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values.

Outcome measures

Measure	Placebo n=5 Participants Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=5 Participants Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=4 Participants Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=3 Participants Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Change From Baseline at Week 12 in Abdomen Visceral Adipose Tissue (AVAT), Abdomen Subcutaneous Adipose Tissue (ASAT), Thigh Subcutaneous Adipose Tissue (TSAT) and Thigh Intermuscular Adipose Tissue (TIAT) AVAT	0.50 Square centimeters Standard Deviation 23.779	7.66 Square centimeters Standard Deviation 11.251	-5.50 Square centimeters Standard Deviation 12.418	2.98 Square centimeters Standard Deviation 5.047
Change From Baseline at Week 12 in Abdomen Visceral Adipose Tissue (AVAT), Abdomen Subcutaneous Adipose Tissue (ASAT), Thigh Subcutaneous Adipose Tissue (TSAT) and Thigh Intermuscular Adipose Tissue (TIAT) ASAT	-3.12 Square centimeters Standard Deviation 6.544	-2.10 Square centimeters Standard Deviation 18.822	22.37 Square centimeters Standard Deviation 43.273	-13.42 Square centimeters Standard Deviation 17.175
Change From Baseline at Week 12 in Abdomen Visceral Adipose Tissue (AVAT), Abdomen Subcutaneous Adipose Tissue (ASAT), Thigh Subcutaneous Adipose Tissue (TSAT) and Thigh Intermuscular Adipose Tissue (TIAT) TSAT	0.73 Square centimeters Standard Deviation 4.366	1.59 Square centimeters Standard Deviation 7.763	6.12 Square centimeters Standard Deviation 7.869	2.90 Square centimeters Standard Deviation 13.194
Change From Baseline at Week 12 in Abdomen Visceral Adipose Tissue (AVAT), Abdomen Subcutaneous Adipose Tissue (ASAT), Thigh Subcutaneous Adipose Tissue (TSAT) and Thigh Intermuscular Adipose Tissue (TIAT) TIAT	0.05 Square centimeters Standard Deviation 0.131	0.12 Square centimeters Standard Deviation 0.399	0.18 Square centimeters Standard Deviation 0.320	0.17 Square centimeters Standard Deviation 0.322

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

GSK232802 25 mg

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

GSK232802 75 mg

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Premarin 0.3 mg

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=90 participants at risk Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 participants at risk；n=878 participants at risk Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=88 participants at risk Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 participants at risk Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Gastrointestinal disorders Abdominal pain	1.1% 1/90 • Up to 21 weeks. Safety Population was used.	0.00% 0/878 • Up to 21 weeks. Safety Population was used.	0.00% 0/88 • Up to 21 weeks. Safety Population was used.	0.00% 0/90 • Up to 21 weeks. Safety Population was used.
Infections and infestations Pneumonia	0.00% 0/90 • Up to 21 weeks. Safety Population was used.	0.00% 0/878 • Up to 21 weeks. Safety Population was used.	1.1% 1/88 • Up to 21 weeks. Safety Population was used.	0.00% 0/90 • Up to 21 weeks. Safety Population was used.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/90 • Up to 21 weeks. Safety Population was used.	0.00% 0/878 • Up to 21 weeks. Safety Population was used.	0.00% 0/88 • Up to 21 weeks. Safety Population was used.	1.1% 1/90 • Up to 21 weeks. Safety Population was used.
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	1.1% 1/90 • Up to 21 weeks. Safety Population was used.	0.00% 0/878 • Up to 21 weeks. Safety Population was used.	0.00% 0/88 • Up to 21 weeks. Safety Population was used.	0.00% 0/90 • Up to 21 weeks. Safety Population was used.

Other adverse events

Measure	Placebo n=90 participants at risk Eligible participants received placebo tablets/capsules to match GSK232802 tablets and Premarin capsules, one tablet or capsule via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 25 mg n=87 participants at risk；n=878 participants at risk Eligible participants received GSK232802 25 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	GSK232802 75 mg n=88 participants at risk Eligible participants received GSK232802 75 mg tablets, one tablet via oral route at approximately the same time each morning for a total period of 12 weeks.	Premarin 0.3 mg n=90 participants at risk Eligible participants received Premarin 0.3 mg capsules, one capsule via oral route at approximately the same time each morning for a total period of 12 weeks.
Infections and infestations Nasopharyngitis	8.9% 8/90 • Up to 21 weeks. Safety Population was used.	3.4% 3/87 • Up to 21 weeks. Safety Population was used.	5.7% 5/88 • Up to 21 weeks. Safety Population was used.	5.6% 5/90 • Up to 21 weeks. Safety Population was used.
Infections and infestations Upper respiratory tract infection	5.6% 5/90 • Up to 21 weeks. Safety Population was used.	4.6% 4/87 • Up to 21 weeks. Safety Population was used.	3.4% 3/88 • Up to 21 weeks. Safety Population was used.	3.3% 3/90 • Up to 21 weeks. Safety Population was used.
Gastrointestinal disorders Nausea	5.6% 5/90 • Up to 21 weeks. Safety Population was used.	6.9% 6/87 • Up to 21 weeks. Safety Population was used.	5.7% 5/88 • Up to 21 weeks. Safety Population was used.	6.7% 6/90 • Up to 21 weeks. Safety Population was used.
Gastrointestinal disorders Diarrhoea	2.2% 2/90 • Up to 21 weeks. Safety Population was used.	6.9% 6/87 • Up to 21 weeks. Safety Population was used.	4.5% 4/88 • Up to 21 weeks. Safety Population was used.	3.3% 3/90 • Up to 21 weeks. Safety Population was used.
Nervous system disorders Headache	15.6% 14/90 • Up to 21 weeks. Safety Population was used.	9.2% 8/87 • Up to 21 weeks. Safety Population was used.	8.0% 7/88 • Up to 21 weeks. Safety Population was used.	3.3% 3/90 • Up to 21 weeks. Safety Population was used.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER