Study Evaluating Bazedoxifene/Conjugated Estrogens Combinations In Postmenopausal Women

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00242710
• Collaborator: (none)
• Enrollment: 1,083
• Locations: 9
• Arms: 4
• Duration (Months): 36
• Patients Per Site: 120.3
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether bazedoxifene/conjugated estrogens combinations are effective for the prevention of endometrial hyperplasia and for the prevention of osteoporosis in postmenopausal women.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Hyperplasia; Osteoporosis	Drug: Bazedoxifene/Conjugated Estrogen; Drug: Bazedoxifene/Conjugated Estrogen; Drug: CE 0.45 mg/MPA 1.5mg; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1083 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Double-Blind, Randomized, Placebo- And Active-Controlled Efficacy And Safety Study Of Bazedoxifene/Conjugated Estrogens Combinations For Prevention Of Endometrial Hyperplasia And Prevention Of Osteoporosis In Postmenopausal Women
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 BZA 20mg/CE 0.625	Drug: Bazedoxifene/Conjugated Estrogen; Subjects will take 1 capsule orally, once daily, at approximately the same time each day continuously for the duration of the study.
Experimental: Arm 2 BZA 20mg/CE 0.45	Drug: Bazedoxifene/Conjugated Estrogen; Subjects will take 1 capsule orally, once daily, at approximately the same time each day continuously for the duration of the study.
Active Comparator: Arm 3 CE 0.45mg/MPA1.5mg	Drug: CE 0.45 mg/MPA 1.5mg; Subjects will take 1 capsule orally, once daily, at approximately the same time each day continuously for the duration of the study.
Placebo Comparator: Arm 4 Placebo	Other: Placebo; Subjects will take 1 capsule orally, once daily, at approximately the same time each day continuously for the duration of the study.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Hyperplasia at Screening [Screening]

   Endometrial hyperplasia was assessed by endometrial biopsies. All endometrial biopsies were read centrally by 2 primary pathologists. Participants were considered to have a diagnosis of hyperplasia if both pathologists read hyperplasia (simple hyperplasia with or without atypia or complex hyperplasia with or without atypia). If the both pathologists disagreed on the presence of hyperplasia, a third pathologist was consulted, with the final diagnosis determined by the majority opinion.

2. Percentage of Participants With Hyperplasia at Month 12 [Month 12]

   Endometrial hyperplasia was assessed by endometrial biopsies. All endometrial biopsies were read centrally by 2 primary pathologists. Participants were considered to have a diagnosis of hyperplasia if both pathologists read hyperplasia (simple hyperplasia with or without atypia or complex hyperplasia with or without atypia). If the both pathologists disagreed on the presence of hyperplasia, a third pathologist was consulted, with the final diagnosis determined by the majority opinion.

3. Bone Mineral Density (BMD) of Lumbar Spine at Screening [Screening]

   BMD measurements of the anteroposterior lumbar spine were acquired by dual-energy x-ray absorptiometry (DXA), twice during screening in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.

4. Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12 [Baseline, Month 12]

   BMD measurements of the anteroposterior lumbar spine were acquired by DXA, twice at Month 12 in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.

5. Bone Mineral Density (BMD) of Total Hip at Screening [Screening]

   BMD measurements of the total hip were acquired by DXA, twice during screening in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.

6. Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 12 [Baseline, Month 12]

   BMD measurements of the total hip were acquired by DXA, twice at Month 12 in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.

Secondary Outcome Measures

1. Percentage of Days With Breast Pain [Screening, Week 1 to 4, 5 to 8, 9 to 12, 13 to 16, 17 to 20, 21 to 24, 25 to 28, 29 to 32, 33 to 36, 37 to 40, 41 to 44, 45 to 48, 49 to 52]

   Percentage of days with breast pain in each 4-week period (for example, Week 1 to 4, 5 to 8) calculated as the number of days on which a participants reported breast pain divided by total number of days with data recorded multiplied by 100. Data was collected every day after randomization up to Year 1 and was analyzed in 4 weeks intervals. Data for screening was not analyzed since data were collected only for 7 days at screening which was not considered comparable to 4-week post-baseline data.

2. Percentage of Participants With Uterine Bleeding or Spotting [Screening, Week 1 to 4, 5 to 8, 9 to 12, 13 to 16, 17 to 20, 21 to 24, 25 to 28, 29 to 32, 33 to 36, 37 to 40, 41 to 44, 45 to 48, 49 to 52]

   Data was collected every day after randomization up to Year 1 and was analyzed in 4 weeks intervals. Data for screening was not analyzed since data were collected only for 7 days at screening which was not considered comparable to 4-week post-baseline data.

3. Percentage of Participants With Hyperplasia at Month 24 [Month 24]

   Endometrial hyperplasia was assessed by endometrial biopsies. All endometrial biopsies were read centrally by 2 primary pathologists. Participants were considered to have a diagnosis of hyperplasia if both pathologists read hyperplasia (simple hyperplasia with or without atypia or complex hyperplasia with or without atypia). If the both pathologists disagreed on the presence of hyperplasia, a third pathologist was consulted, with the final diagnosis determined by the majority opinion.

4. Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 24 [Baseline, Month 24]

   BMD measurements of the anteroposterior lumbar spine were acquired by DXA, twice at Month 24 in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.

5. Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 24 [Baseline, Month 24]

   BMD measurements of the total hip were acquired by DXA, twice at Month 24 in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Generally healthy, postmenopausal women, aged 40 to less than 65 years

• Intact uterus

• At least 12 months of spontaneous amenorrhea, OR 6 months spontaneous amenorrhea with follicle-stimulating hormone (FSH) levels > 40 mIU/mL.

Exclusion Criteria:

• Use of oral estrogen-, progestin-, androgen-, or SERM-containing drug products within 8 weeks before screening (12 weeks for the osteoporosis substudy)

• A history or active presence of clinically important medical disease

• Malabsorption disorders

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Upland	California	United States	91786
2	Pfizer Investigational Site	Inverness	Florida	United States	34452
3	Pfizer Investigational Site	West Palm Beach	Florida	United States	33409
4	Pfizer Investigational Site	Decatur	Georgia	United States	30033
5	Pfizer Investigational Site	Honolulu	Hawaii	United States	96814
6	Pfizer Investigational Site	Lexington	Kentucky	United States	40536-0293
7	Pfizer Investigational Site	Billings	Montana	United States	59102
8	Pfizer Investigational Site	Eugene	Oregon	United States	97401
9	Pfizer Investigational Site	Pittsburgh	Pennsylvania	United States	15206

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00242710
• Other Study ID Numbers: 3115A1-304
• First Posted: Oct 20, 2005
• Last Update Posted: Dec 20, 2013
• Last Verified: Oct 1, 2013

• Keywords provided by Pfizer: Endometrium; Uterus; Menopause
• Additional relevant MeSH terms: Osteoporosis; Endometrial Hyperplasia; Hyperplasia; Bazedoxifene; Estrogens; Estrogens, Conjugated (USP)

Study Results

Participant Flow

Pre-assignment Detail	This main study also included osteoporosis substudy only for the purpose of the assessment of relevant parameters.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Period Title: Core Study (up to Year 1)
STARTED	373	353	183	174
Treated	361	349	179	172
COMPLETED	287	289	132	143
NOT COMPLETED	86	64	51	31
Period Title: Core Study (up to Year 1)
STARTED	287	289	132	143
COMPLETED	168	177	84	94
NOT COMPLETED	119	112	48	49
Period Title: Core Study (up to Year 1)
STARTED	168	177	84	94
COMPLETED	141	148	69	84
NOT COMPLETED	27	29	15	10

Baseline Characteristics

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo	Total
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Total of all reporting groups
Overall Participants	361	349	179	172	1061
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.62 (4.74)	54.44 (4.62)	54.30 (4.56)	54.19 (4.62)	54.44 (4.65)
Sex: Female, Male (Count of Participants)
Female	361 100%	349 100%	179 100%	172 100%	1061 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Hyperplasia at Screening
Description	Endometrial hyperplasia was assessed by endometrial biopsies. All endometrial biopsies were read centrally by 2 primary pathologists. Participants were considered to have a diagnosis of hyperplasia if both pathologists read hyperplasia (simple hyperplasia with or without atypia or complex hyperplasia with or without atypia). If the both pathologists disagreed on the presence of hyperplasia, a third pathologist was consulted, with the final diagnosis determined by the majority opinion.
Time Frame	Screening

Outcome Measure Data

Analysis Population Description

Endometrial hyperplasia at screening was an exclusion criterion and participants who had hyperplasia were not included in the analysis. Therefore this data is not available.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	0	0	0	0

2. Primary Outcome

Title	Percentage of Participants With Hyperplasia at Month 12
Description	Endometrial hyperplasia was assessed by endometrial biopsies. All endometrial biopsies were read centrally by 2 primary pathologists. Participants were considered to have a diagnosis of hyperplasia if both pathologists read hyperplasia (simple hyperplasia with or without atypia or complex hyperplasia with or without atypia). If the both pathologists disagreed on the presence of hyperplasia, a third pathologist was consulted, with the final diagnosis determined by the majority opinion.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

Efficacy evaluable (EE) analysis population for Year 1: all participants who were randomized and took at least 1 dose of test article, who had a screening endometrial biopsy with readings by at least 2 blinded central pathologists, had a biopsy during Month 12, or had hyperplasia diagnosed before Month 12 and had no major protocol violations.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	261	273	119	135
Number (95% Confidence Interval) [percentage of participants]	0.00 0%	1.10 0.3%	0.00 0%	0.00 0%

3. Primary Outcome

Title	Bone Mineral Density (BMD) of Lumbar Spine at Screening
Description	BMD measurements of the anteroposterior lumbar spine were acquired by dual-energy x-ray absorptiometry (DXA), twice during screening in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.
Time Frame	Screening

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (MITT) population for BMD of lumber spine included all randomized participants took at least 1 dose of test article, and had a baseline and at least 1 on-therapy evaluation of BMD (scans acquired more than 60 days after the test article administration was stopped were excluded) at Year 1.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	146	144	60	65
Mean (Standard Deviation) [grams per square centimeter (g/cm^2)]	1.00 (0.12)	1.01 (0.12)	1.02 (0.12)	1.01 (0.12)

4. Primary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12
Description	BMD measurements of the anteroposterior lumbar spine were acquired by DXA, twice at Month 12 in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

MITT population for BMD of lumber spine: all randomized participants who took at least 1 dose of test article, and had a baseline and at least 1 on-therapy evaluation of BMD (scans acquired more than 60 days after test article administration was stopped were excluded) at Year 1. Missing values imputed using last observation carried forward (LOCF).

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	146	144	60	65
Least Squares Mean (Standard Error) [percent change]	0.80 (0.24)	0.80 (0.24)	2.22 (0.37)	-1.56 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	An analysis of covariance (ANCOVA) model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	2.37
	Confidence Interval	(2-Sided) 95%; 1.56 to 3.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.36
	Confidence Interval	(2-Sided) 95%; 1.56 to 3.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.78
	Confidence Interval	(2-Sided) 95%; 2.81 to 4.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Bone Mineral Density (BMD) of Total Hip at Screening
Description	BMD measurements of the total hip were acquired by DXA, twice during screening in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.
Time Frame	Screening

Outcome Measure Data

Analysis Population Description

MITT population for BMD of total hip included all randomized participants who took at least 1 dose of test article, and had a baseline and at least 1 on-therapy evaluation of BMD (scans acquired more than 60 days after the test article administration was stopped were excluded) at Year 1. Missing values were imputed using LOCF method.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	148	145	60	66
Mean (Standard Deviation) [g/cm^2]	0.90 (0.11)	0.89 (0.11)	0.90 (0.10)	0.89 (0.11)

6. Primary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 12
Description	BMD measurements of the total hip were acquired by DXA, twice at Month 12 in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

MITT population for BMD of total hip included all randomized participants who took at least 1 dose of test article, and had a baseline and at least 1 on-therapy evaluation of BMD (scans acquired more than 60 days after the test article administration was stopped were excluded) at Year 1. Missing values were imputed using LOCF method.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	148	145	60	66
Least Squares Mean (Standard Error) [percent change]	0.62 (0.19)	0.84 (0.19)	1.47 (0.29)	-0.99 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95%; 0.97 to 2.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.82
	Confidence Interval	(2-Sided) 95%; 1.19 to 2.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.46
	Confidence Interval	(2-Sided) 95%; 1.69 to 3.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Days With Breast Pain
Description	Percentage of days with breast pain in each 4-week period (for example, Week 1 to 4, 5 to 8) calculated as the number of days on which a participants reported breast pain divided by total number of days with data recorded multiplied by 100. Data was collected every day after randomization up to Year 1 and was analyzed in 4 weeks intervals. Data for screening was not analyzed since data were collected only for 7 days at screening which was not considered comparable to 4-week post-baseline data.
Time Frame	Screening, Week 1 to 4, 5 to 8, 9 to 12, 13 to 16, 17 to 20, 21 to 24, 25 to 28, 29 to 32, 33 to 36, 37 to 40, 41 to 44, 45 to 48, 49 to 52

Outcome Measure Data

Analysis Population Description

MITT population for breast pain: all randomized participants who took at least 1 dose of test article, and had data available at least for 5 of 7 days at screening and 20 days for at least 1 post-baseline interval. n=participants evaluable at specified time periods for each arm, respectively.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	347	329	168	163
Week 1-4 (n=347, 329, 168, 163)	1.55 (0.49)	1.22 (0.51)	3.49 (0.65)	0.89 (0.66)
Week 5-8 (n=331, 323, 158, 158)	1.71 (0.68)	1.58 (0.68)	5.54 (0.91)	1.36 (0.92)
Week 9-12 (n=323, 317, 150, 152)	2.00 (0.68)	1.01 (0.68)	4.80 (0.93)	1.36 (0.92)
Week 13-16 (n=315, 310, 141, 150)	1.87 (0.60)	0.88 (0.61)	3.92 (0.84)	0.77 (0.81)
Week 17-20 (n=313, 309, 141, 149)	2.11 (0.63)	1.57 (0.64)	4.23 (0.88)	1.61 (0.85)
Week 21-24 (n=312, 306, 141, 147)	2.49 (0.78)	1.85 (0.79)	5.01 (1.08)	1.26 (1.06)
Week 25-28 (n=306, 298, 136, 144)	2.60 (0.77)	1.31 (0.78)	4.91 (1.07)	1.39 (1.04)
Week 29-32 (n=301, 297, 133, 143)	1.80 (0.62)	0.82 (0.63)	3.98 (0.87)	0.17 (0.84)
Week 33-36 (n=297, 294, 132, 143)	1.29 (0.57)	0.25 (0.58)	3.49 (0.80)	-0.26 (0.77)
Week 37-40 (n=295, 288, 130, 140)	1.61 (0.62)	0.25 (0.64)	3.87 (0.88)	0.57 (0.85)
Week 41-44 (n=286, 285, 128, 140)	1.99 (0.66)	0.56 (0.67)	2.49 (0.92)	0.86 (0.89)
Week 45-48 (n=282, 284, 127, 140)	1.68 (0.67)	1.26 (0.68)	2.52 (0.94)	1.17 (0.90)
Week 49-52 (n=170, 171, 70, 91)	1.07 (1.12)	1.68 (1.16)	5.27 (1.69)	1.49 (1.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 1-4: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.373
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; -0.80 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 5-8: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.738
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; -1.70 to 2.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 9-12: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.539
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; -1.41 to 2.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 13-16: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.233
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; -0.71 to 2.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 17-20: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.605
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; -1.39 to 2.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 21-24: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.305
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; -1.12 to 3.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 25-28: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.299
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; -1.08 to 3.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 29-32: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.62
	Confidence Interval	(2-Sided) 95%; -0.27 to 3.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 33-36: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.080
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; -0.18 to 3.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 37-40: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.279
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; -0.85 to 2.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 41-44: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.260
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; -0.84 to 3.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 45-48: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.618
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; -1.50 to 2.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 49-52: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.810
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95%; -3.78 to 2.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 1-4: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.654
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.34
	Confidence Interval	(2-Sided) 95%; -1.14 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 5-8: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.834
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.22
	Confidence Interval	(2-Sided) 95%; -1.84 to 2.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 9-12: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.744
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -2.41 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 13-16: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.909
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -1.70 to 1.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 17-20: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.963
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -1.94 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 21-24: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.625
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.59
	Confidence Interval	(2-Sided) 95%; -1.77 to 2.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 25-28: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.947
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -2.39 to 2.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 29-32: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.505
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; -1.25 to 2.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 33-36: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.564
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; -1.23 to 2.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 37-40: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.739
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -2.21 to 1.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 41-44: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.766
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -2.27 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 45-48: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.931
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -1.92 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 49-52: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.911
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -3.17 to 3.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 1-4: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.61
	Confidence Interval	(2-Sided) 95%; 0.92 to 4.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 5-8: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.18
	Confidence Interval	(2-Sided) 95%; 1.79 to 6.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 9-12: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.45
	Confidence Interval	(2-Sided) 95%; 1.03 to 5.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 13-16: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.15
	Confidence Interval	(2-Sided) 95%; 1.01 to 5.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 17-20: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.023
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.61
	Confidence Interval	(2-Sided) 95%; 0.36 to 4.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 21-24: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.75
	Confidence Interval	(2-Sided) 95%; 0.96 to 6.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 25-28: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.52
	Confidence Interval	(2-Sided) 95%; 0.78 to 6.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 29-32: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.81
	Confidence Interval	(2-Sided) 95%; 1.55 to 6.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 33-36: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.75
	Confidence Interval	(2-Sided) 95%; 1.68 to 5.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 37-40: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.30
	Confidence Interval	(2-Sided) 95%; 1.05 to 5.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 41-44: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.175
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.63
	Confidence Interval	(2-Sided) 95%; -0.73 to 3.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 45-48: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.270
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.35
	Confidence Interval	(2-Sided) 95%; -1.05 to 3.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 49-52: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.077
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.78
	Confidence Interval	(2-Sided) 95%; -0.41 to 7.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Uterine Bleeding or Spotting
Description	Data was collected every day after randomization up to Year 1 and was analyzed in 4 weeks intervals. Data for screening was not analyzed since data were collected only for 7 days at screening which was not considered comparable to 4-week post-baseline data.
Time Frame	Screening, Week 1 to 4, 5 to 8, 9 to 12, 13 to 16, 17 to 20, 21 to 24, 25 to 28, 29 to 32, 33 to 36, 37 to 40, 41 to 44, 45 to 48, 49 to 52

Outcome Measure Data

Analysis Population Description

MITT population for uterine bleeding or spotting included all randomized participants who had received at least 1 dose of test article and had at least 1 day of on-therapy bleeding data. Imputation=LOCF. n=participants evaluable for this measure at specified time periods for each arm, respectively.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	330	315	159	155
Week 1-4 (n=330, 313, 159, 155)	5.45 1.5%	4.15 1.2%	19.50 10.9%	4.52 2.6%
Week 5-8 (n=320, 315, 153, 151)	2.19 0.6%	2.86 0.8%	23.53 13.1%	3.31 1.9%
Week 9-12 (n=316, 310, 147, 146)	2.53 0.7%	4.52 1.3%	25.17 14.1%	2.74 1.6%
Week 13-16 (n=310, 296, 137, 149)	2.90 0.8%	2.70 0.8%	16.79 9.4%	1.34 0.8%
Week 17-20 (n=315, 311, 144, 150)	2.22 0.6%	1.61 0.5%	16.67 9.3%	0.67 0.4%
Week 21-24 (n=311, 306, 142, 147)	0.96 0.3%	1.31 0.4%	16.20 9.1%	2.72 1.6%
Week 25-28 (n=294, 290, 131, 143)	2.04 0.6%	1.38 0.4%	9.92 5.5%	2.10 1.2%
Week 29-32 (n=298, 297, 135, 141)	0.67 0.2%	2.02 0.6%	11.11 6.2%	0.71 0.4%
Week 33-36 (n=296, 291, 134, 140)	2.03 0.6%	2.75 0.8%	11.94 6.7%	2.86 1.7%
Week 37-40 (n=282, 279, 131, 139)	2.13 0.6%	2.87 0.8%	11.45 6.4%	2.88 1.7%
Week 41-44 (n=285, 284, 132, 141)	1.40 0.4%	1.06 0.3%	8.33 4.7%	2.84 1.7%
Week 45-48 (n=280, 282, 130, 140)	1.79 0.5%	2.48 0.7%	11.54 6.4%	2.86 1.7%
Week 49-52 (n=45, 51, 15, 31)	0.00 0%	1.96 0.6%	33.33 18.6%	6.45 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 1-4: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.826
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 5-8: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.534
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 9-12: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 13-16: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.516
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 17-20: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.446
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 21-24: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.218
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 25-28: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 29-32: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 33-36: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.733
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 37-40: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.736
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 41-44: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.449
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 45-48: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.489
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	Week 49-52: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.163
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 1-4: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.813
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 5-8: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.777
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 9-12: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.448
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 13-16: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.507
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 17-20: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.669
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 21-24: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.281
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 25-28: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.689
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 29-32: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.437
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 33-36: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 37-40: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 41-44: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.227
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 45-48: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.758
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	Week 49-52: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.554
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 1-4: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 5-8: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 9-12: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 13-16: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 17-20: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 21-24: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 25-28: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 29-32: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 33-36: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 37-40: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 41-44: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 45-48: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	Week 49-52: The Fisher exact test was used for comparisons between groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	Fisher Exact
	Comments

9. Secondary Outcome

Title	Percentage of Participants With Hyperplasia at Month 24
Description	Endometrial hyperplasia was assessed by endometrial biopsies. All endometrial biopsies were read centrally by 2 primary pathologists. Participants were considered to have a diagnosis of hyperplasia if both pathologists read hyperplasia (simple hyperplasia with or without atypia or complex hyperplasia with or without atypia). If the both pathologists disagreed on the presence of hyperplasia, a third pathologist was consulted, with the final diagnosis determined by the majority opinion.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

EE analysis population for Year 2 included all randomized participants who took at least 1 dose of test article, participated in study extension, had a screening endometrial biopsy with readings by at least 2 blinded central pathologists, had biopsy during Month 24, or had hyperplasia diagnosed before Month 24 and had no major protocol violations.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	131	142	66	79
Number (95% Confidence Interval) [percentage of participants]	0.00 0%	4.93 1.4%	0.00 0%	0.00 0%

10. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 24
Description	BMD measurements of the anteroposterior lumbar spine were acquired by DXA, twice at Month 24 in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.
Time Frame	Baseline, Month 24

Outcome Measure Data

Analysis Population Description

MITT population for BMD of lumber spine: all participants who took at least 1 dose of test article, participated in study extension, and had a baseline and at least 1 on-therapy evaluation of BMD (scans acquired more than 60 days after the test article administration was stopped were excluded) at Year 2. Missing values imputed using LOCF method.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	87	87	40	39
Least Squares Mean (Standard Error) [percent change]	0.96 (0.40)	0.86 (0.41)	2.39 (0.57)	-2.29 (0.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.25
	Confidence Interval	(2-Sided) 95%; 1.92 to 4.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.14
	Confidence Interval	(2-Sided) 95%; 1.83 to 4.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.68
	Confidence Interval	(2-Sided) 95%; 3.13 to 6.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 24
Description	BMD measurements of the total hip were acquired by DXA, twice at Month 24 in participants who entered the osteoporosis substudy. The second scan was to be performed on the same day as the first; however, the participant was to be removed completely from the table after the first scan and repositioned for the second scan. An average of the 2 readings was reported.
Time Frame	Baseline, Month 24

Outcome Measure Data

Analysis Population Description

MITT population for BMD of total hip: all participants who took at least 1 dose of test article, participated in study extension, and had a baseline and at least 1 on-therapy evaluation of BMD (scans acquired more than 60 days after the test article administration was stopped were excluded) at Year 2. Missing values imputed using LOCF method.

Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg	Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.	Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.	Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
Measure Participants	87	88	40	39
Least Squares Mean (Standard Error) [percent change]	0.30 (0.31)	0.41 (0.32)	0.85 (0.44)	-1.53 (0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.83
	Confidence Interval	(2-Sided) 95%; 0.80 to 2.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.94
	Confidence Interval	(2-Sided) 95%; 0.92 to 2.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg, Placebo
	Comments	An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.38
	Confidence Interval	(2-Sided) 95%; 1.17 to 3.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg		Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg		Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg		Placebo
Arm/Group Description	Bazedoxifene 20 milligram (mg)/conjugated estrogen 0.45 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 international unit (IU) orally once daily up to Year 2.		Bazedoxifene 20 mg/conjugated estrogen 0.625 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.		Conjugated estrogen 0.45 mg/medroxyprogesterone acetate 1.5 mg capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.		Placebo matched to bazedoxifene/conjugated estrogen or conjugated estrogen/medroxyprogesterone acetate capsule orally once daily at approximately the same time each day continuously up to Year 1 during the core study and up to Year 2 during the study extension. Participants also received Caltrate plus D tablet containing calcium 600 mg and vitamin D 200 IU orally once daily up to Year 2.
All Cause Mortality
	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg		Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg		Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg		Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg		Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/361 (6.1%)		19/349 (5.4%)		7/179 (3.9%)		7/172 (4.1%)
Blood and lymphatic system disorders
Febrile neutropenia	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Cardiac disorders
Coronary artery disease	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Myocardial infarction	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Eye disorders
Vitreous haemorrhage	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Gastrointestinal disorders
Abdominal pain	0/361 (0%)		3/349 (0.9%)		1/179 (0.6%)		0/172 (0%)
Faecal incontinence	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Gastritis	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Nausea	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Small intestinal obstruction	0/361 (0%)		0/349 (0%)		1/179 (0.6%)		0/172 (0%)
Vomiting	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		1/172 (0.6%)
General disorders
Chest pain	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Non-cardiac chest pain	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Sudden death	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Hepatobiliary disorders
Cholecystitis	1/361 (0.3%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Cholecystitis acute	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Cholecystitis chronic	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Infections and infestations
Arthritis infective	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Cellulitis	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Pelvic abscess	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Pneumonia	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Ankle fracture	2/361 (0.6%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Cervical vertebral fracture	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Concussion	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Lung injury	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Medication error	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Multiple drug overdose	0/361 (0%)		0/349 (0%)		1/179 (0.6%)		0/172 (0%)
Intentional overdose	2/361 (0.6%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Rib fracture	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Road traffic accident	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Tendon rupture	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Tibia fracture	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Investigations
Biopsy endometrium abnormal	1/361 (0.3%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Musculoskeletal chest pain	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Synovitis	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Basal cell carcinoma	0/361 (0%)		3/349 (0.9%)		1/179 (0.6%)		0/172 (0%)
Lung adenocarcinoma stage III	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Malignant melanoma	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		2/172 (1.2%)
Ovarian germ cell teratoma benign	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Squamous cell carcinoma of skin	1/361 (0.3%)		0/349 (0%)		1/179 (0.6%)		1/172 (0.6%)
Tonsil cancer	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Nervous system disorders
Transient ischaemic attack	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Psychiatric disorders
Alcohol abuse	0/361 (0%)		0/349 (0%)		1/179 (0.6%)		0/172 (0%)
Completed suicide	0/361 (0%)		0/349 (0%)		1/179 (0.6%)		0/172 (0%)
Major depression	0/361 (0%)		0/349 (0%)		1/179 (0.6%)		0/172 (0%)
Renal and urinary disorders
Calculus ureteric	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Stress urinary incontinence	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Reproductive system and breast disorders
Cervical dysplasia	0/361 (0%)		1/349 (0.3%)		0/179 (0%)		0/172 (0%)
Cystocele	0/361 (0%)		0/349 (0%)		1/179 (0.6%)		0/172 (0%)
Fibrocystic breast disease	0/361 (0%)		0/349 (0%)		1/179 (0.6%)		0/172 (0%)
Ovarian mass	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Rectocele	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Vaginal prolapse	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Respiratory, thoracic and mediastinal disorders
Asthmatic crisis	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Pneumothorax	0/361 (0%)		0/349 (0%)		0/179 (0%)		1/172 (0.6%)
Surgical and medical procedures
Hip arthroplasty	1/361 (0.3%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Vascular disorders
Deep vein thrombosis	3/361 (0.8%)		0/349 (0%)		0/179 (0%)		0/172 (0%)
Other (Not Including Serious) Adverse Events
	Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg		Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg		Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	322/361 (89.2%)		309/349 (88.5%)		165/179 (92.2%)		152/172 (88.4%)
Blood and lymphatic system disorders
Lymphadenopathy	0/361 (0%)		5/349 (1.4%)		2/179 (1.1%)		4/172 (2.3%)
Cardiac disorders
Palpitations	7/361 (1.9%)		0/349 (0%)		2/179 (1.1%)		4/172 (2.3%)
Ear and labyrinth disorders
Ear pain	3/361 (0.8%)		4/349 (1.1%)		4/179 (2.2%)		1/172 (0.6%)
Vertigo	3/361 (0.8%)		7/349 (2%)		1/179 (0.6%)		2/172 (1.2%)
Gastrointestinal disorders
Abdominal distension	5/361 (1.4%)		6/349 (1.7%)		8/179 (4.5%)		3/172 (1.7%)
Abdominal pain	20/361 (5.5%)		28/349 (8%)		17/179 (9.5%)		5/172 (2.9%)
Abdominal pain lower	10/361 (2.8%)		17/349 (4.9%)		9/179 (5%)		3/172 (1.7%)
Abdominal pain upper	32/361 (8.9%)		22/349 (6.3%)		12/179 (6.7%)		7/172 (4.1%)
Constipation	23/361 (6.4%)		16/349 (4.6%)		9/179 (5%)		9/172 (5.2%)
Diarrhoea	21/361 (5.8%)		22/349 (6.3%)		11/179 (6.1%)		14/172 (8.1%)
Dyspepsia	19/361 (5.3%)		21/349 (6%)		11/179 (6.1%)		18/172 (10.5%)
Flatulence	2/361 (0.6%)		7/349 (2%)		3/179 (1.7%)		3/172 (1.7%)
Gastrooesophageal reflux disease	10/361 (2.8%)		7/349 (2%)		2/179 (1.1%)		2/172 (1.2%)
Nausea	25/361 (6.9%)		20/349 (5.7%)		14/179 (7.8%)		10/172 (5.8%)
Stomach discomfort	8/361 (2.2%)		10/349 (2.9%)		7/179 (3.9%)		4/172 (2.3%)
Toothache	19/361 (5.3%)		19/349 (5.4%)		12/179 (6.7%)		4/172 (2.3%)
Vomiting	11/361 (3%)		10/349 (2.9%)		8/179 (4.5%)		5/172 (2.9%)
General disorders
Fatigue	10/361 (2.8%)		13/349 (3.7%)		7/179 (3.9%)		8/172 (4.7%)
Non-cardiac chest pain	6/361 (1.7%)		7/349 (2%)		4/179 (2.2%)		7/172 (4.1%)
Oedema peripheral	9/361 (2.5%)		10/349 (2.9%)		4/179 (2.2%)		4/172 (2.3%)
Pain	17/361 (4.7%)		15/349 (4.3%)		3/179 (1.7%)		12/172 (7%)
Pyrexia	4/361 (1.1%)		5/349 (1.4%)		4/179 (2.2%)		6/172 (3.5%)
Immune system disorders
Hypersensitivity	10/361 (2.8%)		9/349 (2.6%)		3/179 (1.7%)		2/172 (1.2%)
Seasonal allergy	11/361 (3%)		7/349 (2%)		5/179 (2.8%)		5/172 (2.9%)
Infections and infestations
Bronchitis	17/361 (4.7%)		18/349 (5.2%)		7/179 (3.9%)		13/172 (7.6%)
Gastroenteritis	6/361 (1.7%)		10/349 (2.9%)		9/179 (5%)		4/172 (2.3%)
Gastroenteritis viral	11/361 (3%)		12/349 (3.4%)		6/179 (3.4%)		3/172 (1.7%)
Influenza	43/361 (11.9%)		35/349 (10%)		24/179 (13.4%)		14/172 (8.1%)
Localised infection	2/361 (0.6%)		4/349 (1.1%)		4/179 (2.2%)		1/172 (0.6%)
Nasopharyngitis	83/361 (23%)		82/349 (23.5%)		42/179 (23.5%)		30/172 (17.4%)
Onychomycosis	2/361 (0.6%)		4/349 (1.1%)		5/179 (2.8%)		1/172 (0.6%)
Oral herpes	3/361 (0.8%)		4/349 (1.1%)		5/179 (2.8%)		1/172 (0.6%)
Pharyngitis	11/361 (3%)		7/349 (2%)		6/179 (3.4%)		6/172 (3.5%)
Sinusitis	32/361 (8.9%)		23/349 (6.6%)		9/179 (5%)		13/172 (7.6%)
Tooth abscess	7/361 (1.9%)		7/349 (2%)		4/179 (2.2%)		7/172 (4.1%)
Tooth infection	5/361 (1.4%)		7/349 (2%)		8/179 (4.5%)		5/172 (2.9%)
Upper respiratory tract infection	29/361 (8%)		35/349 (10%)		15/179 (8.4%)		12/172 (7%)
Urinary tract infection	26/361 (7.2%)		21/349 (6%)		11/179 (6.1%)		9/172 (5.2%)
Vulvovaginal mycotic infection	12/361 (3.3%)		20/349 (5.7%)		16/179 (8.9%)		2/172 (1.2%)
Injury, poisoning and procedural complications
Arthropod bite	6/361 (1.7%)		8/349 (2.3%)		3/179 (1.7%)		1/172 (0.6%)
Back injury	4/361 (1.1%)		7/349 (2%)		1/179 (0.6%)		2/172 (1.2%)
Contusion	3/361 (0.8%)		8/349 (2.3%)		3/179 (1.7%)		1/172 (0.6%)
Excoriation	2/361 (0.6%)		1/349 (0.3%)		4/179 (2.2%)		1/172 (0.6%)
Fall	4/361 (1.1%)		7/349 (2%)		2/179 (1.1%)		2/172 (1.2%)
Joint sprain	8/361 (2.2%)		8/349 (2.3%)		3/179 (1.7%)		2/172 (1.2%)
Muscle strain	4/361 (1.1%)		6/349 (1.7%)		3/179 (1.7%)		4/172 (2.3%)
Post procedural haemorrhage	8/361 (2.2%)		5/349 (1.4%)		4/179 (2.2%)		2/172 (1.2%)
Procedural pain	16/361 (4.4%)		20/349 (5.7%)		9/179 (5%)		12/172 (7%)
Investigations
Weight increased	10/361 (2.8%)		8/349 (2.3%)		4/179 (2.2%)		8/172 (4.7%)
Metabolism and nutrition disorders
Hypercholesterolaemia	6/361 (1.7%)		3/349 (0.9%)		5/179 (2.8%)		4/172 (2.3%)
Hyperlipidaemia	14/361 (3.9%)		6/349 (1.7%)		6/179 (3.4%)		13/172 (7.6%)
Obesity	2/361 (0.6%)		0/349 (0%)		2/179 (1.1%)		4/172 (2.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	55/361 (15.2%)		56/349 (16%)		22/179 (12.3%)		28/172 (16.3%)
Arthritis	2/361 (0.6%)		9/349 (2.6%)		2/179 (1.1%)		0/172 (0%)
Back pain	60/361 (16.6%)		66/349 (18.9%)		33/179 (18.4%)		23/172 (13.4%)
Muscle spasms	37/361 (10.2%)		29/349 (8.3%)		16/179 (8.9%)		10/172 (5.8%)
Musculoskeletal pain	16/361 (4.4%)		13/349 (3.7%)		8/179 (4.5%)		9/172 (5.2%)
Musculoskeletal stiffness	7/361 (1.9%)		7/349 (2%)		2/179 (1.1%)		4/172 (2.3%)
Myalgia	34/361 (9.4%)		28/349 (8%)		16/179 (8.9%)		16/172 (9.3%)
Neck pain	17/361 (4.7%)		17/349 (4.9%)		11/179 (6.1%)		14/172 (8.1%)
Osteoarthritis	11/361 (3%)		1/349 (0.3%)		2/179 (1.1%)		3/172 (1.7%)
Osteoporosis	3/361 (0.8%)		7/349 (2%)		1/179 (0.6%)		5/172 (2.9%)
Pain in extremity	39/361 (10.8%)		39/349 (11.2%)		19/179 (10.6%)		27/172 (15.7%)
Pain in jaw	3/361 (0.8%)		0/349 (0%)		4/179 (2.2%)		1/172 (0.6%)
Nervous system disorders
Dizziness	13/361 (3.6%)		19/349 (5.4%)		11/179 (6.1%)		5/172 (2.9%)
Headache	94/361 (26%)		78/349 (22.3%)		58/179 (32.4%)		41/172 (23.8%)
Migraine	7/361 (1.9%)		11/349 (3.2%)		6/179 (3.4%)		3/172 (1.7%)
Sciatica	3/361 (0.8%)		3/349 (0.9%)		0/179 (0%)		4/172 (2.3%)
Sinus headache	28/361 (7.8%)		14/349 (4%)		5/179 (2.8%)		9/172 (5.2%)
Tension headache	1/361 (0.3%)		2/349 (0.6%)		4/179 (2.2%)		3/172 (1.7%)
Psychiatric disorders
Anxiety	10/361 (2.8%)		4/349 (1.1%)		7/179 (3.9%)		6/172 (3.5%)
Depression	6/361 (1.7%)		9/349 (2.6%)		6/179 (3.4%)		7/172 (4.1%)
Insomnia	25/361 (6.9%)		17/349 (4.9%)		10/179 (5.6%)		13/172 (7.6%)
Renal and urinary disorders
Haematuria	2/361 (0.6%)		3/349 (0.9%)		3/179 (1.7%)		5/172 (2.9%)
Reproductive system and breast disorders
Breast pain	18/361 (5%)		18/349 (5.2%)		19/179 (10.6%)		7/172 (4.1%)
Endometrial hyperplasia	0/361 (0%)		7/349 (2%)		0/179 (0%)		0/172 (0%)
Endometrial hypertrophy	5/361 (1.4%)		7/349 (2%)		4/179 (2.2%)		1/172 (0.6%)
Genital haemorrhage	18/361 (5%)		29/349 (8.3%)		28/179 (15.6%)		10/172 (5.8%)
Metrorrhagia	9/361 (2.5%)		4/349 (1.1%)		10/179 (5.6%)		4/172 (2.3%)
Uterine haemorrhage	2/361 (0.6%)		2/349 (0.6%)		7/179 (3.9%)		1/172 (0.6%)
Uterine spasm	4/361 (1.1%)		2/349 (0.6%)		7/179 (3.9%)		1/172 (0.6%)
Vaginal discharge	7/361 (1.9%)		10/349 (2.9%)		6/179 (3.4%)		3/172 (1.7%)
Vaginal haemorrhage	13/361 (3.6%)		18/349 (5.2%)		22/179 (12.3%)		4/172 (2.3%)
Vulvovaginal pruritus	7/361 (1.9%)		5/349 (1.4%)		6/179 (3.4%)		1/172 (0.6%)
Respiratory, thoracic and mediastinal disorders
Cough	21/361 (5.8%)		20/349 (5.7%)		17/179 (9.5%)		9/172 (5.2%)
Nasal congestion	9/361 (2.5%)		8/349 (2.3%)		6/179 (3.4%)		4/172 (2.3%)
Pharyngolaryngeal pain	21/361 (5.8%)		19/349 (5.4%)		11/179 (6.1%)		16/172 (9.3%)
Pulmonary congestion	2/361 (0.6%)		10/349 (2.9%)		4/179 (2.2%)		1/172 (0.6%)
Rhinorrhoea	2/361 (0.6%)		3/349 (0.9%)		1/179 (0.6%)		5/172 (2.9%)
Sinus congestion	14/361 (3.9%)		15/349 (4.3%)		6/179 (3.4%)		3/172 (1.7%)
Skin and subcutaneous tissue disorders
Dermatitis contact	7/361 (1.9%)		7/349 (2%)		5/179 (2.8%)		3/172 (1.7%)
Night sweats	6/361 (1.7%)		7/349 (2%)		3/179 (1.7%)		4/172 (2.3%)
Rash	9/361 (2.5%)		16/349 (4.6%)		7/179 (3.9%)		6/172 (3.5%)
Vascular disorders
Hot flush	38/361 (10.5%)		37/349 (10.6%)		11/179 (6.1%)		7/172 (4.1%)
Hypertension	14/361 (3.9%)		11/349 (3.2%)		7/179 (3.9%)		6/172 (3.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.