Study Evaluating The Effects Of Bazedoxifene/Conjugated Estrogens On Endometrial Safety And Postmenopausal Osteoporosis

A Double-Blind, Randomized, Placebo And Active- Controlled Efficacy And Safety Study Of The Effects Of Bazedoxifene/Conjugated Estrogens Combinations On Endometrial Hyperplasia And Prevention Of Osteoporosis In Postmenopausal Women

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00808132

Enrollment

1886

Registered

2008-12-15

Start date

2009-01-31

Completion date

2011-02-28

Last updated

2014-04-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Menopause, Osteoporosis

Keywords

Postmenopausal Women, Bazedoxifene/Conjugated Estrogens

Brief summary

The purpose of this research study is to evaluate the safety and effectiveness of this investigational drug for the treatment of menopausal symptoms while protecting the endometrium (uterine lining) and preventing postmenopausal osteoporosis. Subject participation will last approximately 14.5 months.

Interventions

DRUGbazedoxifene 20 mg/ conjugated estrogens 0.45 mg

One capsule, bazedoxifene 20 mg/conjugated estrogens 0.45 mg (over-encapsulated), once a day for one year.

DRUGbazedoxifene 20 mg/ conjugated estrogens 0.625 mg

One capsule, bazedoxifene 20 mg/conjugated estrogens 0.625 mg (over-encapsulated), once a day for one year.

DRUGbazedoxifene 20 mg

One capsule, bazedoxifene 20 mg (over-encapsulated), once a day for one year.

DRUGconjugated estrogens 0.45 mg/ medroxyprogesterone acetate 1.5 mg

One capsule, conjugated estrogens 0.45 mg and medroxyprogesterone 1.5 mg (over-encapsulated), once a day for one year.

DRUGPlacebo

One capsule, placebo (over-encapsulated), once a day for one year.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

40 Years to 64 Years

Healthy volunteers

Inclusion criteria

* Generally healthy, postmenopausal women, aged 40 to 64 seeking treatment for menopausal symptoms * At least 12 months of spontaneous amenorrhea, OR 6 months spontaneous amenorrhea with follicle-stimulating hormone (FSH) levels \> 40 mIU/mL * Intact Uterus

Exclusion criteria

* Use of oral estrogen, progestin, androgen, or selective estrogen receptor modulator (SERM) containing drug products within 8 weeks before screening * A history or active presence of clinically important medical disease: eg. cardiovascular disease (stroke, heart attack), chronic renal or liver disease, breast cancer, etc.

Design outcomes

Primary

Measure	Time frame	Description
Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12: Osteoporosis Sub-Study	Baseline, Month 12	BMD measurements of the anteroposterior lumbar spine were acquired by using dual-energy x-ray absorptiometry (DXA) scans, twice at Month 12 for a subset of 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. Mean percentage change from baseline of the 2 readings were reported.
Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Month 12	Endometrial hyperplasia was assessed by endometrial biopsies. All endometrial biopsies were read centrally by 2 primary pathologists. If both the pathologists disagreed on the presence of hyperplasia, a third pathologist was consulted. Results were summarized for two definitions of hyperplasia (simple hyperplasia with or without atypia or complex hyperplasia with or without atypia); definition 1: participants were considered to have a diagnosis of hyperplasia when the 3 pathologists disagreed but at least 1 pathologist determined hyperplasia; definition 2: participants were considered to have a diagnosis of hyperplasia if at least 2 of the 3 pathologists agreed on the diagnosis.

Secondary

Measure	Time frame	Description
Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 6, 12: Osteoporosis Sub-Study	Baseline, Month 6, Month 12	BMD measurements of the total hip were acquired by using DXA scans, twice at Month 6 and 12 for a subset of 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. Mean percentage change from baseline of the 2 readings were reported.
Percentage of Participants With Cumulative Amenorrhea: Main Study	Day 1 up to Day 364	Cumulative amenorrhea was defined as the absence of any bleeding or spotting for cumulative 4-week periods throughout 1-year study.
Percent Change From Baseline in Breast Density at Month 12: Breast Density Sub-Study	Baseline, Month 12	Breast density was assessed by digitalized mammograms which were centrally read by a single radiologist using specifically-developed software. Breast density was assessed for subset of participants who entered the breast density sub-study
Percent Change From Baseline in Bone Turnover Markers (BTMs) at Month 6 and Month 12: Osteoporosis Sub-Study	Baseline, Month 6, 12	Bone turnover is the removal of old bone from the body and its replacement by new bone. Bone turnover markers included serum osteocalcin, C-telopeptide, and procollagen type 1 N-propeptide (P1NP), were measured at Month 6 and Month 12 for a subset of participants who entered the osteoporosis substudy. Blood samples were collected to evaluate bone turnover markers levels.
Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Baseline, Month 3	Participant-rated questionnaire to assess sleep quality and quantity. Consists of 12-item questionnaires answered on a range of 1 to 6 for questions (Q) 3 to 12, 1 to 5 for Q1 (some questions are reversed so that a high score reflects more of the attributes); and Q2 answered on 0 to 24. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. The items contribute to each scale and are averaged to create the 7 scale scores and a sleep quantity scale. Scales with at least one item answered was used to generate a scale score. Scales include; sleep disturbance (SD), snoring, awaken short of breath (ASoB) or with a headache (H), somnolence, sleep adequacy (SA), sleep problem index (SPI) I and II (range: 0-100) and sleep quantity (SQ \[range 0 to 24\]). Except for sleep quantity, higher scores=greater impairment.
Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Baseline	MENQOL questionnaire assessed how bothered participants were due to menopause. It consists of 29 items divided into 4 domains: vasomotor function (3 items), psychosocial function (7 items), physical function (16 items), and sexual function (3 items). Each item scores a range from 1 to 8, with 1 indicating that the participant did not experience the symptom or problem, 8 indicating that the participant was extremely bothered by the symptom or problem. The total score for each domain is the average of item scores and ranged from 1 to 8 with higher score indicating worsening of symptoms. The MENQOL total score is the mean of these 4 domain scores and ranged from 1 to 8 with higher score indicating worsening of symptoms.
Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Baseline, Month 3	MENQOL questionnaire assessed how bothered participants were due to menopause. It consists of 29 items divided into 4 domains: vasomotor function (3 items), psychosocial function (7 items), physical function (16 items), and sexual function (3 items). Each item scores a range from 1 to 8, with 1 indicating that the participant did not experience the symptom or problem, 8 indicating that the participant was extremely bothered by the symptom or problem. The total score for each domain is the average of item scores and ranged from 1 to 8 with higher score indicating worsening of symptoms. The MENQOL total score is the mean of these 4 domain scores and ranged from 1 to 8 with higher score indicating worsening of symptoms.
Percentage of Participants With Uterine Bleeding	Week 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 25-28, 29-32, 33-36, 37-40, 41-44, 45-48, 49-52	Percentage of participants with uterine bleeding were calculated for each 4-week period for 1-year on therapy.
Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Baseline	Participant-rated questionnaire to assess sleep quality and quantity. Consists of 12-item questionnaires answered on a range of 1 to 6 for questions (Q) 3 to 12, 1 to 5 for Q1 (some questions are reversed so that a high score reflects more of the attributes); and Q2 answered on 0 to 24. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. The items contribute to each scale and are averaged to create the 7 scale scores and a sleep quantity scale. Scales with at least one item answered was used to generate a scale score. Scales include; sleep disturbance (SD), snoring, awaken short of breath (ASoB) or with a headache (H), somnolence, sleep adequacy (SA), sleep problem index (SPI) I and II (range: 0-100) and sleep quantity (SQ \[range 0 to 24\]). Except for sleep quantity, higher scores=greater impairment.
Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 6: Osteoporosis Sub-Study	Baseline, Month 6	BMD measurements of the anteroposterior lumbar spine were acquired by using DXA scans, twice at Month 6 for a subset of 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. Mean percentage change from baseline of the 2 readings were reported.

Other

Measure	Time frame	Description
Percentage of Participants With Breast Tenderness	Screening, Week 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 25-28, 29-32, 33-36, 37-40, 41-44, 45-48, 49-52	Percentage of participants who reported at least 1 day of breast tenderness during each 4-week period for 1-year on therapy was calculated.

Countries

Argentina, Australia, Chile, Colombia, Denmark, Finland, Hungary, Mexico, New Zealand, Norway, Poland, United States

Participant flow

Pre-assignment details

This main study also included 3 sub-studies only for the purpose of the assessment of relevant parameters: breast density sub-study, osteoporosis sub-study (OSS), and sleep sub-study. A participant could participate in more than 1 sub-study.

Participants by arm

Arm	Count
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg Bazedoxifene 20 milligram (mg), conjugated estrogens 0.45 mg tablets-in-capsule orally once daily at approximately the same time each day continuously for 1 year.	445
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg Bazedoxifene 20 mg, conjugated estrogens 0.625 mg tablets-in-capsule orally once daily at approximately the same time each day continuously for 1 year.	474
Bazedoxifene 20 mg Bazedoxifene 20 mg tablet-in-capsule orally once daily at approximately the same time each day continuously for 1 year.	230
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg Conjugated estrogens 0.45 mg, medroxyprogesterone acetate 1.5 mg tablets-in-capsule orally once daily at approximately the same time each day continuously for 1 year.	220
Placebo Placebo capsule matched to bazedoxifene/conjugated estrogen or bazedoxifene alone or conjugated estrogen/medroxyprogesterone acetate tablets-in-capsule orally once daily at approximately the same time each day continuously for 1 year.	474
Total	1,843

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	34	33	16	31	33
Overall Study	Death	0	0	0	0	1
Overall Study	Lost to Follow-up	8	10	11	8	9
Overall Study	Other	6	4	6	2	15
Overall Study	Physician Decision	0	1	0	0	0
Overall Study	Protocol Violation	8	9	4	9	5
Overall Study	Randomized, but not treated	10	7	9	8	9
Overall Study	Unsatisfactory response	5	6	6	4	12
Overall Study	Withdrawal by Subject	27	18	2	7	16

Baseline characteristics

Characteristic	Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Bazedoxifene 20 mg	Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Placebo	Total
Age, Continuous	54.43 Years STANDARD_DEVIATION 4.02	53.89 Years STANDARD_DEVIATION 4	54.07 Years STANDARD_DEVIATION 4.01	54.15 Years STANDARD_DEVIATION 4.5	54.19 Years STANDARD_DEVIATION 4.07	54.15 Years STANDARD_DEVIATION 4.09
Sex: Female, Male Female	445 Participants	474 Participants	230 Participants	220 Participants	474 Participants	1843 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	407 / 445	426 / 474	207 / 230	197 / 220	423 / 474
serious Total, serious adverse events	16 / 445	17 / 474	5 / 230	13 / 220	18 / 474

Outcome results

Primary

Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study

Endometrial hyperplasia was assessed by endometrial biopsies. All endometrial biopsies were read centrally by 2 primary pathologists. If both the pathologists disagreed on the presence of hyperplasia, a third pathologist was consulted. Results were summarized for two definitions of hyperplasia (simple hyperplasia with or without atypia or complex hyperplasia with or without atypia); definition 1: participants were considered to have a diagnosis of hyperplasia when the 3 pathologists disagreed but at least 1 pathologist determined hyperplasia; definition 2: participants were considered to have a diagnosis of hyperplasia if at least 2 of the 3 pathologists agreed on the diagnosis.

Time frame: Month 12

Population: Efficacy evaluable (EE) population included all randomized participants who took at least 1 dose of study drug, 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	Measure	Group	Value (NUMBER)
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 1	0.30 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 2	0.30 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 1	0.54 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 2	0.27 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 1	0.00 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 2	0.00 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 2	0.00 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 1	0.00 Percentage of Participants
Placebo	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 1	0.85 Percentage of Participants
Placebo	Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study	Definition 2	0.28 Percentage of Participants

Primary

Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12: Osteoporosis Sub-Study

BMD measurements of the anteroposterior lumbar spine were acquired by using dual-energy x-ray absorptiometry (DXA) scans, twice at Month 12 for a subset of 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. Mean percentage change from baseline of the 2 readings were reported.

Time frame: Baseline, Month 12

Population: Modified Intent-to-Treat (MITT) population included all randomized participants who met inclusion criteria for osteoporosis sub-study, who had taken at least 1 dose of the study drug, and had a baseline and at least 1 post baseline value. Last Observation Carried Forward (LOCF) method was used to impute missing values.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12: Osteoporosis Sub-Study	0.24 Percent Change	Standard Error 0.29
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12: Osteoporosis Sub-Study	0.60 Percent Change	Standard Error 0.27
Bazedoxifene 20 mg	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12: Osteoporosis Sub-Study	0.07 Percent Change	Standard Error 0.4
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12: Osteoporosis Sub-Study	1.30 Percent Change	Standard Error 0.39
Placebo	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12: Osteoporosis Sub-Study	-1.28 Percent Change	Standard Error 0.28

Comparison: ANCOVA model was used with treatment and region as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [1.209, 2.533]ANCOVA

Comparison: Analysis of covariance (ANCOVA) model was used with treatment and region as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [0.822, 2.201]ANCOVA

Secondary

Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study

Participant-rated questionnaire to assess sleep quality and quantity. Consists of 12-item questionnaires answered on a range of 1 to 6 for questions (Q) 3 to 12, 1 to 5 for Q1 (some questions are reversed so that a high score reflects more of the attributes); and Q2 answered on 0 to 24. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range\* 100); total score range: 0 to 100; higher score = greater intensity of attribute. The items contribute to each scale and are averaged to create the 7 scale scores and a sleep quantity scale. Scales with at least one item answered was used to generate a scale score. Scales include; sleep disturbance (SD), snoring, awaken short of breath (ASoB) or with a headache (H), somnolence, sleep adequacy (SA), sleep problem index (SPI) I and II (range: 0-100) and sleep quantity (SQ \[range 0 to 24\]). Except for sleep quantity, higher scores=greater impairment.

Time frame: Baseline, Month 3

Population: MITT population included all randomized participants who met inclusion criteria for sleep sub-study and had baseline and at least 1 post-baseline evaluation for the respective endpoint. Here N = maximum number of participants who were evaluable for this outcome and n = participants who were evaluable at specified time points for each arm.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	-17.27 Units on a Scale	Standard Error 2.01
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	-5.86 Units on a Scale	Standard Error 1.83
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	ASoB or H (n=112,121,47,52,111)	-4.26 Units on a Scale	Standard Error 1.41
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Somnolence (n=112,121,47,52,111)	-10.54 Units on a Scale	Standard Error 1.53
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	14.22 Units on a Scale	Standard Error 2.4
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	-13.19 Units on a Scale	Standard Error 1.51
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI II (n=112, 121, 47, 52,111)	-14.01 Units on a Scale	Standard Error 1.51
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	0.28 Units on a Scale	Standard Error 0.1
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	ASoB or H (n=112,121,47,52,111)	-5.81 Units on a Scale	Standard Error 1.35
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	-13.99 Units on a Scale	Standard Error 1.46
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	-18.18 Units on a Scale	Standard Error 1.94
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Somnolence (n=112,121,47,52,111)	-9.72 Units on a Scale	Standard Error 1.48
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	-5.38 Units on a Scale	Standard Error 1.76
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	0.44 Units on a Scale	Standard Error 0.09
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	14.30 Units on a Scale	Standard Error 2.32
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI II (n=112, 121, 47, 52,111)	-14.53 Units on a Scale	Standard Error 1.46
Bazedoxifene 20 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI II (n=112, 121, 47, 52,111)	-9.64 Units on a Scale	Standard Error 2.21
Bazedoxifene 20 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	0.32 Units on a Scale	Standard Error 0.14
Bazedoxifene 20 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Somnolence (n=112,121,47,52,111)	-6.12 Units on a Scale	Standard Error 2.25
Bazedoxifene 20 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	-8.92 Units on a Scale	Standard Error 2.21
Bazedoxifene 20 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	ASoB or H (n=112,121,47,52,111)	-3.12 Units on a Scale	Standard Error 2.06
Bazedoxifene 20 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	-2.54 Units on a Scale	Standard Error 2.67
Bazedoxifene 20 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	-11.64 Units on a Scale	Standard Error 2.94
Bazedoxifene 20 mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	9.10 Units on a Scale	Standard Error 3.52
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	-2.90 Units on a Scale	Standard Error 2.55
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	ASoB or H (n=112,121,47,52,111)	-3.62 Units on a Scale	Standard Error 1.95
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Somnolence (n=112,121,47,52,111)	-7.36 Units on a Scale	Standard Error 2.14
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	15.10 Units on a Scale	Standard Error 3.34
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	-13.71 Units on a Scale	Standard Error 2.09
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	0.41 Units on a Scale	Standard Error 0.13
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	-18.01 Units on a Scale	Standard Error 2.79
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI II (n=112, 121, 47, 52,111)	-14.12 Units on a Scale	Standard Error 2.1
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Somnolence (n=112,121,47,52,111)	-10.55 Units on a Scale	Standard Error 1.53
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	0.36 Units on a Scale	Standard Error 0.1
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	ASoB or H (n=112,121,47,52,111)	-3.63 Units on a Scale	Standard Error 1.4
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI II (n=112, 121, 47, 52,111)	-12.04 Units on a Scale	Standard Error 1.51
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	-14.34 Units on a Scale	Standard Error 2.01
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	-11.84 Units on a Scale	Standard Error 1.5
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	-2.71 Units on a Scale	Standard Error 1.84
Placebo	Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	11.46 Units on a Scale	Standard Error 2.4

Comparison: Sleep disturbance: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.25395% CI: [-7.96, 2.1]ANCOVA

Comparison: Sleep disturbance: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.12795% CI: [-8.78, 1.1]ANCOVA

Comparison: Snoring: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.1895% CI: [-7.76, 1.46]ANCOVA

Comparison: Snoring: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.24795% CI: [-7.19, 1.85]ANOVA

Comparison: ASoB: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.72695% CI: [-4.15, 2.9]ANCOVA

Comparison: ASoB: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.21895% CI: [-5.63, 1.29]ANCOVA

Comparison: Somnolence: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.99695% CI: [-3.85, 3.87]ANCOVA

Comparison: Somnolence: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.66595% CI: [-2.94, 4.6]ANCOVA

Comparison: Sleep adequacy: Month 3, ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.36895% CI: [-3.26, 8.78]ANOVA

Comparison: Sleep adequacy: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.34595% CI: [-3.07, 8.75]ANCOVA

Comparison: Sleep problem index I: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.48295% CI: [-5.12, 2.42]ANCOVA

Comparison: Sleep problem index I: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.25495% CI: [-5.86, 1.55]ANCOVA

Comparison: Sleep problem index II: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.30895% CI: [-5.76, 1.82]ANCOVA

Comparison: Sleep problem index II: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.1995% CI: [-6.2, 1.23]ANCOVA

Comparison: Sleep quantity: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.5595% CI: [-0.32, 0.17]ANCOVA

Comparison: Sleep quantity: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.47795% CI: [-0.15, 0.32]ANCOVA

Secondary

Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study

MENQOL questionnaire assessed how bothered participants were due to menopause. It consists of 29 items divided into 4 domains: vasomotor function (3 items), psychosocial function (7 items), physical function (16 items), and sexual function (3 items). Each item scores a range from 1 to 8, with 1 indicating that the participant did not experience the symptom or problem, 8 indicating that the participant was extremely bothered by the symptom or problem. The total score for each domain is the average of item scores and ranged from 1 to 8 with higher score indicating worsening of symptoms. The MENQOL total score is the mean of these 4 domain scores and ranged from 1 to 8 with higher score indicating worsening of symptoms.

Time frame: Baseline, Month 3

Population: MITT population included all randomized participants who met inclusion criteria for sleep sub-study and had baseline and at least 1 post-baseline evaluation for the respective endpoint. Here N: maximum number of participants who were evaluable for this outcome and n: participants who were evaluable at specified time points for each arm.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	-1.20 Units on a Scale	Standard Error 0.16
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	-2.37 Units on a Scale	Standard Error 0.17
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	-1.27 Units on a Scale	Standard Error 0.1
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	-0.67 Units on a Scale	Standard Error 0.12
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	-0.92 Units on a Scale	Standard Error 0.1
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	-1.40 Units on a Scale	Standard Error 0.15
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	-1.11 Units on a Scale	Standard Error 0.1
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	-0.84 Units on a Scale	Standard Error 0.12
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	-1.53 Units on a Scale	Standard Error 0.1
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	-2.75 Units on a Scale	Standard Error 0.17
Bazedoxifene 20 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	-0.67 Units on a Scale	Standard Error 0.15
Bazedoxifene 20 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	-1.25 Units on a Scale	Standard Error 0.25
Bazedoxifene 20 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	-0.47 Units on a Scale	Standard Error 0.18
Bazedoxifene 20 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	-0.09 Units on a Scale	Standard Error 0.23
Bazedoxifene 20 mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	-0.63 Units on a Scale	Standard Error 0.15
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	-1.39 Units on a Scale	Standard Error 0.14
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	-3.19 Units on a Scale	Standard Error 0.24
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	-0.76 Units on a Scale	Standard Error 0.22
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	-0.76 Units on a Scale	Standard Error 0.14
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	-0.83 Units on a Scale	Standard Error 0.17
Placebo	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	-0.87 Units on a Scale	Standard Error 0.1
Placebo	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	-1.04 Units on a Scale	Standard Error 0.16
Placebo	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	-1.45 Units on a Scale	Standard Error 0.17
Placebo	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	-1.03 Units on a Scale	Standard Error 0.1
Placebo	Change From Baseline in Menopause-Specific Quality of Life (MENQOL) Score at Month 3: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	-0.74 Units on a Scale	Standard Error 0.12

Comparison: Vasomotor function: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: <0.001ANCOVA

Comparison: Psychosocial function: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.68ANCOVA

Comparison: Psychosocial function: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.493ANCOVA

Comparison: Physical function: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.698ANCOVA

Comparison: Physical function: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.055ANCOVA

Comparison: Sexual function: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.428ANCOVA

Comparison: Sexual function: ANCOVA model was used with treatment and region as factors and baseline as a covariate.p-value: 0.071ANCOVA

Secondary

Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study

Time frame: Baseline

Arm	Measure	Group	Value (MEAN)	Dispersion
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	48.9 Units on a Scale	Standard Deviation 22.9
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	32.1 Units on a Scale	Standard Deviation 30.1
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	ASoB or H (n=112, 121, 47,52,111)	12.5 Units on a Scale	Standard Deviation 19.2
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Somnolence (n=112, 121, 47, 52, 111)	36.3 Units on a Scale	Standard Deviation 21.6
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	39.3 Units on a Scale	Standard Deviation 24.3
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	44.5 Units on a Scale	Standard Deviation 17.3
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI II (n=112, 121, 47, 52, 111)	45.5 Units on a Scale	Standard Deviation 17.2
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	6.2 Units on a Scale	Standard Deviation 1.1
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	ASoB or H (n=112, 121, 47,52,111)	11.9 Units on a Scale	Standard Deviation 19.4
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	42.0 Units on a Scale	Standard Deviation 16.7
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	48.2 Units on a Scale	Standard Deviation 21.7
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Somnolence (n=112, 121, 47, 52, 111)	30.0 Units on a Scale	Standard Deviation 20.1
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	27.6 Units on a Scale	Standard Deviation 26.9
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	6.1 Units on a Scale	Standard Deviation 1.1
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	41.7 Units on a Scale	Standard Deviation 23.9
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI II (n=112, 121, 47, 52, 111)	43.2 Units on a Scale	Standard Deviation 16.8
Bazedoxifene 20 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI II (n=112, 121, 47, 52, 111)	46.4 Units on a Scale	Standard Deviation 18
Bazedoxifene 20 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	5.9 Units on a Scale	Standard Deviation 1.1
Bazedoxifene 20 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Somnolence (n=112, 121, 47, 52, 111)	34.6 Units on a Scale	Standard Deviation 23.5
Bazedoxifene 20 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	44.7 Units on a Scale	Standard Deviation 18.2
Bazedoxifene 20 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	ASoB or H (n=112, 121, 47,52,111)	13.2 Units on a Scale	Standard Deviation 20.1
Bazedoxifene 20 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	37.9 Units on a Scale	Standard Deviation 30.7
Bazedoxifene 20 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	50.5 Units on a Scale	Standard Deviation 24.4
Bazedoxifene 20 mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	37.4 Units on a Scale	Standard Deviation 23.2
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	33.1 Units on a Scale	Standard Deviation 29.6
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	ASoB or H (n=112, 121, 47,52,111)	13.1 Units on a Scale	Standard Deviation 20.2
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Somnolence (n=112, 121, 47, 52, 111)	28.7 Units on a Scale	Standard Deviation 19.4
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	36.5 Units on a Scale	Standard Deviation 20.6
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	44.9 Units on a Scale	Standard Deviation 16
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	6.2 Units on a Scale	Standard Deviation 1.3
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	50.4 Units on a Scale	Standard Deviation 21.1
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI II (n=112, 121, 47, 52, 111)	45.2 Units on a Scale	Standard Deviation 16.1
Placebo	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Somnolence (n=112, 121, 47, 52, 111)	31.2 Units on a Scale	Standard Deviation 19.2
Placebo	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SQ (n=111, 121, 47, 52, 111)	6.2 Units on a Scale	Standard Deviation 1.1
Placebo	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	ASoB or H (n=112, 121, 47,52,111)	12.1 Units on a Scale	Standard Deviation 20.4
Placebo	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI II (n=112, 121, 47, 52, 111)	43.7 Units on a Scale	Standard Deviation 18.3
Placebo	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SD (n=112, 121, 47, 52, 111)	47.8 Units on a Scale	Standard Deviation 24.6
Placebo	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SPI I (n=112, 121, 47, 52, 111)	43.4 Units on a Scale	Standard Deviation 18.1
Placebo	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	Snoring (n=110, 121, 47, 51, 108)	34.4 Units on a Scale	Standard Deviation 30.5
Placebo	Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study	SA (n=112, 121, 47, 52, 111)	40.3 Units on a Scale	Standard Deviation 23.6

Secondary

Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study

Time frame: Baseline

Arm	Measure	Group	Value (MEAN)	Dispersion
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	3.74 Units on a Scale	Standard Deviation 2.2
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	5.40 Units on a Scale	Standard Deviation 1.564
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	4.07 Units on a Scale	Standard Deviation 1.227
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	3.46 Units on a Scale	Standard Deviation 1.716
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	3.74 Units on a Scale	Standard Deviation 1.377
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	3.63 Units on a Scale	Standard Deviation 2.182
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	3.58 Units on a Scale	Standard Deviation 1.385
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	3.41 Units on a Scale	Standard Deviation 1.628
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	4.05 Units on a Scale	Standard Deviation 1.246
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	5.60 Units on a Scale	Standard Deviation 1.468
Bazedoxifene 20 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	3.96 Units on a Scale	Standard Deviation 1.475
Bazedoxifene 20 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	5.87 Units on a Scale	Standard Deviation 1.246
Bazedoxifene 20 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	3.49 Units on a Scale	Standard Deviation 1.663
Bazedoxifene 20 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	4.05 Units on a Scale	Standard Deviation 2.265
Bazedoxifene 20 mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	4.34 Units on a Scale	Standard Deviation 1.156
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	4.15 Units on a Scale	Standard Deviation 1.314
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	5.65 Units on a Scale	Standard Deviation 1.62
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	3.73 Units on a Scale	Standard Deviation 2.238
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	3.74 Units on a Scale	Standard Deviation 1.409
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	3.48 Units on a Scale	Standard Deviation 1.793
Placebo	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Physical function (n=111, 121, 47, 52, 112)	3.58 Units on a Scale	Standard Deviation 1.445
Placebo	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Sexual function (n=110, 121, 47, 52, 112)	3.83 Units on a Scale	Standard Deviation 2.243
Placebo	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Vasomotor function (n=111, 121, 47, 52, 112)	5.62 Units on a Scale	Standard Deviation 1.596
Placebo	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	MENQOL Total Score (n=110, 121, 47, 52, 112)	4.06 Units on a Scale	Standard Deviation 1.155
Placebo	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: Sleep Sub-Study	Psychosocial function (n=111, 121, 47, 52, 112)	3.22 Units on a Scale	Standard Deviation 1.522

Secondary

Percentage of Participants With Cumulative Amenorrhea: Main Study

Cumulative amenorrhea was defined as the absence of any bleeding or spotting for cumulative 4-week periods throughout 1-year study.

Time frame: Day 1 up to Day 364

Population: MITT population included all randomized participants who received at least 1 dose of the study drug, and had at least 1 day of on-therapy bleeding data. Here N signifies participants who were evaluable for this outcome measure.

Arm	Measure	Value (NUMBER)
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Cumulative Amenorrhea: Main Study	87.89 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Cumulative Amenorrhea: Main Study	84.87 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Cumulative Amenorrhea: Main Study	82.35 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Cumulative Amenorrhea: Main Study	54.43 Percentage of Participants
Placebo	Percentage of Participants With Cumulative Amenorrhea: Main Study	83.91 Percentage of Participants

p-value: 0.138Fisher Exact

p-value: <0.001Fisher Exact

p-value: 0.765Fisher Exact

p-value: <0.001Fisher Exact

Secondary

Percentage of Participants With Uterine Bleeding

Percentage of participants with uterine bleeding were calculated for each 4-week period for 1-year on therapy.

Time frame: Week 1-4, 5-8, 9-12, 13-16, 17-20, 21-24, 25-28, 29-32, 33-36, 37-40, 41-44, 45-48, 49-52

Population: MITT population included all randomized participants who took at least 1 dose of the study drug, and had at least 1 day of on-therapy bleeding data. Here N signifies participants who were evaluable for this outcome measure and n signifies participants who were evaluable at specified time points for each arm respectively.

Arm	Measure	Group	Value (NUMBER)
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 29-32 (n=376, 416, 194, 173, 405)	1.60 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 41-44 (n=363, 396, 188, 162, 386)	1.38 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 13-16 (n=415, 446, 213, 196, 446)	2.41 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 45-48 (n=358, 394, 188, 160, 383)	0.84 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 49-52 (n=357, 392, 187, 159, 380)	1.68 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 9-12 (n=417, 451, 217, 199, 452)	2.16 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 37-40 (n=373, 411, 191, 168, 394)	1.61 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 17-20 (n=399,426,201,184,427)	2.26 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 1-4 (n=440, 468, 229, 216, 470)	3.86 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 5-8 (n=428, 458, 221, 205, 462)	4.44 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 25-28 (n=393, 422, 197, 182, 420)	2.04 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 33-36 (n=373, 413, 192, 170, 399)	0.54 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.45 mg	Percentage of Participants With Uterine Bleeding	Week 21-24 (n=395, 424, 199, 183, 423)	2.78 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 41-44 (n=363, 396, 188, 162, 386)	1.26 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 5-8 (n=428, 458, 221, 205, 462)	5.02 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 29-32 (n=376, 416, 194, 173, 405)	1.68 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 25-28 (n=393, 422, 197, 182, 420)	2.13 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 1-4 (n=440, 468, 229, 216, 470)	6.20 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 45-48 (n=358, 394, 188, 160, 383)	2.28 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 9-12 (n=417, 451, 217, 199, 452)	3.55 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 49-52 (n=357, 392, 187, 159, 380)	1.28 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 21-24 (n=395, 424, 199, 183, 423)	2.12 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 13-16 (n=415, 446, 213, 196, 446)	2.91 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 37-40 (n=373, 411, 191, 168, 394)	2.92 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 17-20 (n=399,426,201,184,427)	2.58 Percentage of Participants
Bazedoxifene 20 mg / Conjugated Estrogens 0.625 mg	Percentage of Participants With Uterine Bleeding	Week 33-36 (n=373, 413, 192, 170, 399)	2.91 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 25-28 (n=393, 422, 197, 182, 420)	1.02 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 1-4 (n=440, 468, 229, 216, 470)	5.68 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 5-8 (n=428, 458, 221, 205, 462)	3.62 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 9-12 (n=417, 451, 217, 199, 452)	2.76 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 13-16 (n=415, 446, 213, 196, 446)	3.29 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 17-20 (n=399,426,201,184,427)	2.49 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 21-24 (n=395, 424, 199, 183, 423)	2.01 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 29-32 (n=376, 416, 194, 173, 405)	1.55 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 33-36 (n=373, 413, 192, 170, 399)	2.08 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 37-40 (n=373, 411, 191, 168, 394)	1.57 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 41-44 (n=363, 396, 188, 162, 386)	0.00 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 45-48 (n=358, 394, 188, 160, 383)	0.53 Percentage of Participants
Bazedoxifene 20 mg	Percentage of Participants With Uterine Bleeding	Week 49-52 (n=357, 392, 187, 159, 380)	1.07 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 13-16 (n=415, 446, 213, 196, 446)	24.49 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 41-44 (n=363, 396, 188, 162, 386)	13.58 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 1-4 (n=440, 468, 229, 216, 470)	20.83 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 37-40 (n=373, 411, 191, 168, 394)	14.29 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 5-8 (n=428, 458, 221, 205, 462)	24.39 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 49-52 (n=357, 392, 187, 159, 380)	8.81 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 45-48 (n=358, 394, 188, 160, 383)	14.38 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 25-28 (n=393, 422, 197, 182, 420)	14.84 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 17-20 (n=399,426,201,184,427)	18.48 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 33-36 (n=373, 413, 192, 170, 399)	12.94 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 21-24 (n=395, 424, 199, 183, 423)	18.58 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 9-12 (n=417, 451, 217, 199, 452)	25.63 Percentage of Participants
Conjugated Estrogens 0.45mg/Medroxyprogesterone Acetate 1.5mg	Percentage of Participants With Uterine Bleeding	Week 29-32 (n=376, 416, 194, 173, 405)	12.14 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 49-52 (n=357, 392, 187, 159, 380)	1.58 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 17-20 (n=399,426,201,184,427)	3.51 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 1-4 (n=440, 468, 229, 216, 470)	4.68 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 33-36 (n=373, 413, 192, 170, 399)	2.26 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 13-16 (n=415, 446, 213, 196, 446)	3.36 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 37-40 (n=373, 411, 191, 168, 394)	4.82 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 9-12 (n=417, 451, 217, 199, 452)	4.42 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 29-32 (n=376, 416, 194, 173, 405)	1.73 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 41-44 (n=363, 396, 188, 162, 386)	1.55 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 5-8 (n=428, 458, 221, 205, 462)	4.11 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 25-28 (n=393, 422, 197, 182, 420)	3.33 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 21-24 (n=395, 424, 199, 183, 423)	3.31 Percentage of Participants
Placebo	Percentage of Participants With Uterine Bleeding	Week 45-48 (n=358, 394, 188, 160, 383)	2.09 Percentage of Participants

Comparison: Week 1-4: The Fisher exact test was used for comparisons between groups.p-value: 0.624Fisher Exact

Comparison: Week 5-8: The Fisher exact test was used for comparisons between groups.p-value: 0.868Fisher Exact

Comparison: Week 9-12: The Fisher exact test was used for comparisons between groups.p-value: 0.087Fisher Exact

Comparison: Week 13-16: The Fisher exact test was used for comparisons between groups.p-value: 0.425Fisher Exact

Comparison: Week 17-20: The Fisher exact test was used for comparisons between groups.p-value: 0.307Fisher Exact

Comparison: Week 21-24: The Fisher exact test was used for comparisons between groups.p-value: 0.689Fisher Exact

Comparison: Week 25-28: The Fisher exact test was used for comparisons between groups.p-value: 0.285Fisher Exact

Comparison: Week 29-32: The Fisher exact test was used for comparisons between groups.p-value: 1Fisher Exact

Comparison: Week 33-36: The Fisher exact test was used for comparisons between groups.p-value: 0.065Fisher Exact

Comparison: Week 37-40: The Fisher exact test was used for comparisons between groups.p-value: 0.014Fisher Exact

Comparison: Week 41-44: The Fisher exact test was used for comparisons between groups.p-value: 1Fisher Exact

Comparison: Week 45-48: The Fisher exact test was used for comparisons between groups.p-value: 0.226Fisher Exact

Comparison: Week 49-52: The Fisher exact test was used for comparisons between groups.p-value: 1Fisher Exact

Comparison: Week 1-4: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 5-8: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 9-12: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 13-16: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 17-20: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 21-24: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 25-28: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 29-32: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 33-36: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 37-40: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 41-44: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 45-48: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 49-52: The Fisher exact test was used for comparisons between groups.p-value: <0.001Fisher Exact

Comparison: Week 1-4: The Fisher exact test was used for comparisons between groups.p-value: 0.317Fisher Exact

Comparison: Week 5-8: The Fisher exact test was used for comparisons between groups.p-value: 0.531Fisher Exact

Comparison: Week 9-12: The Fisher exact test was used for comparisons between groups.p-value: 0.61Fisher Exact

Comparison: Week 13-16: The Fisher exact test was used for comparisons between groups.p-value: 0.848Fisher Exact

Comparison: Week 17-20: The Fisher exact test was used for comparisons between groups.p-value: 0.551Fisher Exact

Comparison: Week 21-24: The Fisher exact test was used for comparisons between groups.p-value: 0.3Fisher Exact

Comparison: Week 25-28: The Fisher exact test was used for comparisons between groups.p-value: 0.299Fisher Exact

Comparison: Week 29-32: The Fisher exact test was used for comparisons between groups.p-value: 1Fisher Exact

Comparison: Week 33-36: The Fisher exact test was used for comparisons between groups.p-value: 0.66Fisher Exact

Comparison: Week 37-40: The Fisher exact test was used for comparisons between groups.p-value: 0.199Fisher Exact

Comparison: Week 41-44: The Fisher exact test was used for comparisons between groups.p-value: 0.77Fisher Exact

Comparison: Week 45-48: The Fisher exact test was used for comparisons between groups.p-value: 1Fisher Exact

Comparison: Week 49-52: The Fisher exact test was used for comparisons between groups.p-value: 0.769Fisher Exact