Endometrial Hyperplasia, Osteoporosis
Conditions
Keywords
Endometrium, Uterus, Menopause
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.
Interventions
Subjects will take 1 capsule orally, once daily, at approximately the same time each day continuously for the duration of the study.
DRUGCE 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.
OTHERPlacebo
Subjects will take 1 capsule orally, once daily, at approximately the same time each day continuously for the duration of the study.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
This main study also included osteoporosis substudy only for the purpose of the assessment of relevant parameters.
Participants by arm
| Arm | Count |
|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg 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. | 361 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg 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. | 349 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg 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. | 179 |
| Placebo 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. | 172 |
| Total | 1,061 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Core Study (up to Year 1) | Adverse Event | 30 | 25 | 23 | 14 |
| Core Study (up to Year 1) | Death | 0 | 0 | 1 | 0 |
| Core Study (up to Year 1) | Lack of Efficacy | 1 | 0 | 0 | 0 |
| Core Study (up to Year 1) | Lost to Follow-up | 8 | 8 | 7 | 3 |
| Core Study (up to Year 1) | Other | 6 | 1 | 0 | 2 |
| Core Study (up to Year 1) | Physician Decision | 0 | 1 | 0 | 1 |
| Core Study (up to Year 1) | Protocol Violation | 2 | 9 | 1 | 3 |
| Core Study (up to Year 1) | Randomized but not Treated | 12 | 4 | 4 | 2 |
| Core Study (up to Year 1) | Withdrawal by Subject | 27 | 16 | 15 | 6 |
| Period Between Core Study and Extension | Adverse Event | 2 | 3 | 5 | 2 |
| Period Between Core Study and Extension | Extension not Available | 17 | 21 | 8 | 7 |
| Period Between Core Study and Extension | Other | 24 | 24 | 9 | 11 |
| Period Between Core Study and Extension | Physician Decision | 1 | 1 | 0 | 0 |
| Period Between Core Study and Extension | Protocol Violation | 0 | 0 | 2 | 1 |
| Period Between Core Study and Extension | Withdrawal by Subject | 75 | 63 | 24 | 28 |
| Study Extension (up to Year 2) | Adverse Event | 7 | 9 | 2 | 4 |
| Study Extension (up to Year 2) | Death | 0 | 0 | 0 | 1 |
| Study Extension (up to Year 2) | Lost to Follow-up | 7 | 7 | 5 | 0 |
| Study Extension (up to Year 2) | Other | 3 | 5 | 4 | 3 |
| Study Extension (up to Year 2) | Protocol Violation | 0 | 2 | 0 | 1 |
| Study Extension (up to Year 2) | Withdrawal by Subject | 10 | 6 | 4 | 1 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|
| Age Continuous | 54.62 years STANDARD_DEVIATION 4.74 | 54.44 years STANDARD_DEVIATION 4.62 | 54.30 years STANDARD_DEVIATION 4.56 | 54.19 years STANDARD_DEVIATION 4.62 | 54.44 years STANDARD_DEVIATION 4.65 |
| Sex: Female, Male Female | 361 Participants | 349 Participants | 179 Participants | 172 Participants | 1061 Participants |
| Sex: Female, Male Male | 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 |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 322 / 361 | 309 / 349 | 165 / 179 | 152 / 172 |
| serious Total, serious adverse events | 22 / 361 | 19 / 349 | 7 / 179 | 7 / 172 |
Outcome results
Primary
Bone Mineral Density (BMD) of Lumbar Spine at 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.
Time frame: Screening
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Bone Mineral Density (BMD) of Lumbar Spine at Screening | 1.00 grams per square centimeter (g/cm^2) | Standard Deviation 0.12 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Bone Mineral Density (BMD) of Lumbar Spine at Screening | 1.01 grams per square centimeter (g/cm^2) | Standard Deviation 0.12 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Bone Mineral Density (BMD) of Lumbar Spine at Screening | 1.02 grams per square centimeter (g/cm^2) | Standard Deviation 0.12 |
| Placebo | Bone Mineral Density (BMD) of Lumbar Spine at Screening | 1.01 grams per square centimeter (g/cm^2) | Standard Deviation 0.12 |
Primary
Bone Mineral Density (BMD) of Total Hip at 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.
Time frame: Screening
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Bone Mineral Density (BMD) of Total Hip at Screening | 0.90 g/cm^2 | Standard Deviation 0.11 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Bone Mineral Density (BMD) of Total Hip at Screening | 0.89 g/cm^2 | Standard Deviation 0.11 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Bone Mineral Density (BMD) of Total Hip at Screening | 0.90 g/cm^2 | Standard Deviation 0.1 |
| Placebo | Bone Mineral Density (BMD) of Total Hip at Screening | 0.89 g/cm^2 | Standard Deviation 0.11 |
Primary
Percentage of Participants With Hyperplasia at 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.
Time frame: Month 12
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Hyperplasia at Month 12 | 0.00 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Hyperplasia at Month 12 | 1.10 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Hyperplasia at Month 12 | 0.00 percentage of participants |
| Placebo | Percentage of Participants With Hyperplasia at Month 12 | 0.00 percentage of participants |
Primary
Percentage of Participants With Hyperplasia at 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.
Time frame: Screening
Population: 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.
Primary
Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at 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.
Time frame: Baseline, Month 12
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12 | 0.80 percent change | Standard Error 0.24 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12 | 0.80 percent change | Standard Error 0.24 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12 | 2.22 percent change | Standard Error 0.37 |
| Placebo | Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12 | -1.56 percent change | Standard Error 0.35 |
Comparison: An analysis of covariance (ANCOVA) model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [1.56, 3.18]ANCOVA
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [1.56, 3.17]ANCOVA
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [2.81, 4.76]ANCOVA
Primary
Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at 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.
Time frame: Baseline, Month 12
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 12 | 0.62 percent change | Standard Error 0.19 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 12 | 0.84 percent change | Standard Error 0.19 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 12 | 1.47 percent change | Standard Error 0.29 |
| Placebo | Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 12 | -0.99 percent change | Standard Error 0.27 |
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [0.97, 2.24]ANCOVA
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [1.19, 2.46]ANCOVA
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [1.69, 3.23]ANCOVA
Secondary
Percentage of Days With Breast Pain
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 1-4 (n=347, 329, 168, 163) | 1.55 percentage of days | Standard Error 0.49 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 5-8 (n=331, 323, 158, 158) | 1.71 percentage of days | Standard Error 0.68 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 9-12 (n=323, 317, 150, 152) | 2.00 percentage of days | Standard Error 0.68 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 13-16 (n=315, 310, 141, 150) | 1.87 percentage of days | Standard Error 0.6 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 17-20 (n=313, 309, 141, 149) | 2.11 percentage of days | Standard Error 0.63 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 21-24 (n=312, 306, 141, 147) | 2.49 percentage of days | Standard Error 0.78 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 25-28 (n=306, 298, 136, 144) | 2.60 percentage of days | Standard Error 0.77 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 29-32 (n=301, 297, 133, 143) | 1.80 percentage of days | Standard Error 0.62 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 33-36 (n=297, 294, 132, 143) | 1.29 percentage of days | Standard Error 0.57 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 37-40 (n=295, 288, 130, 140) | 1.61 percentage of days | Standard Error 0.62 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 41-44 (n=286, 285, 128, 140) | 1.99 percentage of days | Standard Error 0.66 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 45-48 (n=282, 284, 127, 140) | 1.68 percentage of days | Standard Error 0.67 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Days With Breast Pain | Week 49-52 (n=170, 171, 70, 91) | 1.07 percentage of days | Standard Error 1.12 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 13-16 (n=315, 310, 141, 150) | 0.88 percentage of days | Standard Error 0.61 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 49-52 (n=170, 171, 70, 91) | 1.68 percentage of days | Standard Error 1.16 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 41-44 (n=286, 285, 128, 140) | 0.56 percentage of days | Standard Error 0.67 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 29-32 (n=301, 297, 133, 143) | 0.82 percentage of days | Standard Error 0.63 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 9-12 (n=323, 317, 150, 152) | 1.01 percentage of days | Standard Error 0.68 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 1-4 (n=347, 329, 168, 163) | 1.22 percentage of days | Standard Error 0.51 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 37-40 (n=295, 288, 130, 140) | 0.25 percentage of days | Standard Error 0.64 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 33-36 (n=297, 294, 132, 143) | 0.25 percentage of days | Standard Error 0.58 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 21-24 (n=312, 306, 141, 147) | 1.85 percentage of days | Standard Error 0.79 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 17-20 (n=313, 309, 141, 149) | 1.57 percentage of days | Standard Error 0.64 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 5-8 (n=331, 323, 158, 158) | 1.58 percentage of days | Standard Error 0.68 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 45-48 (n=282, 284, 127, 140) | 1.26 percentage of days | Standard Error 0.68 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Days With Breast Pain | Week 25-28 (n=306, 298, 136, 144) | 1.31 percentage of days | Standard Error 0.78 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 41-44 (n=286, 285, 128, 140) | 2.49 percentage of days | Standard Error 0.92 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 13-16 (n=315, 310, 141, 150) | 3.92 percentage of days | Standard Error 0.84 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 17-20 (n=313, 309, 141, 149) | 4.23 percentage of days | Standard Error 0.88 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 49-52 (n=170, 171, 70, 91) | 5.27 percentage of days | Standard Error 1.69 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 21-24 (n=312, 306, 141, 147) | 5.01 percentage of days | Standard Error 1.08 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 25-28 (n=306, 298, 136, 144) | 4.91 percentage of days | Standard Error 1.07 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 45-48 (n=282, 284, 127, 140) | 2.52 percentage of days | Standard Error 0.94 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 29-32 (n=301, 297, 133, 143) | 3.98 percentage of days | Standard Error 0.87 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 33-36 (n=297, 294, 132, 143) | 3.49 percentage of days | Standard Error 0.8 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 37-40 (n=295, 288, 130, 140) | 3.87 percentage of days | Standard Error 0.88 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 1-4 (n=347, 329, 168, 163) | 3.49 percentage of days | Standard Error 0.65 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 5-8 (n=331, 323, 158, 158) | 5.54 percentage of days | Standard Error 0.91 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Days With Breast Pain | Week 9-12 (n=323, 317, 150, 152) | 4.80 percentage of days | Standard Error 0.93 |
| Placebo | Percentage of Days With Breast Pain | Week 37-40 (n=295, 288, 130, 140) | 0.57 percentage of days | Standard Error 0.85 |
| Placebo | Percentage of Days With Breast Pain | Week 29-32 (n=301, 297, 133, 143) | 0.17 percentage of days | Standard Error 0.84 |
| Placebo | Percentage of Days With Breast Pain | Week 13-16 (n=315, 310, 141, 150) | 0.77 percentage of days | Standard Error 0.81 |
| Placebo | Percentage of Days With Breast Pain | Week 1-4 (n=347, 329, 168, 163) | 0.89 percentage of days | Standard Error 0.66 |
| Placebo | Percentage of Days With Breast Pain | Week 25-28 (n=306, 298, 136, 144) | 1.39 percentage of days | Standard Error 1.04 |
| Placebo | Percentage of Days With Breast Pain | Week 21-24 (n=312, 306, 141, 147) | 1.26 percentage of days | Standard Error 1.06 |
| Placebo | Percentage of Days With Breast Pain | Week 9-12 (n=323, 317, 150, 152) | 1.36 percentage of days | Standard Error 0.92 |
| Placebo | Percentage of Days With Breast Pain | Week 5-8 (n=331, 323, 158, 158) | 1.36 percentage of days | Standard Error 0.92 |
| Placebo | Percentage of Days With Breast Pain | Week 17-20 (n=313, 309, 141, 149) | 1.61 percentage of days | Standard Error 0.85 |
| Placebo | Percentage of Days With Breast Pain | Week 33-36 (n=297, 294, 132, 143) | -0.26 percentage of days | Standard Error 0.77 |
| Placebo | Percentage of Days With Breast Pain | Week 49-52 (n=170, 171, 70, 91) | 1.49 percentage of days | Standard Error 1.5 |
| Placebo | Percentage of Days With Breast Pain | Week 45-48 (n=282, 284, 127, 140) | 1.17 percentage of days | Standard Error 0.9 |
| Placebo | Percentage of Days With Breast Pain | Week 41-44 (n=286, 285, 128, 140) | 0.86 percentage of days | Standard Error 0.89 |
Comparison: Week 1-4: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.37395% CI: [-0.8, 2.12]ANCOVA
Comparison: Week 5-8: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.73895% CI: [-1.7, 2.4]ANCOVA
Comparison: Week 9-12: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.53995% CI: [-1.41, 2.71]ANCOVA
Comparison: Week 13-16: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.23395% CI: [-0.71, 2.9]ANCOVA
Comparison: Week 17-20: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.60595% CI: [-1.39, 2.39]ANCOVA
Comparison: Week 21-24: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.30595% CI: [-1.12, 3.57]ANCOVA
Comparison: Week 25-28: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.29995% CI: [-1.08, 3.52]ANCOVA
Comparison: Week 29-32: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.09295% CI: [-0.27, 3.51]ANCOVA
Comparison: Week 33-36: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.0895% CI: [-0.18, 3.29]ANCOVA
Comparison: Week 37-40: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.27995% CI: [-0.85, 2.92]ANCOVA
Comparison: Week 41-44: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.2695% CI: [-0.84, 3.11]ANCOVA
Comparison: Week 45-48: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.61895% CI: [-1.5, 2.52]ANCOVA
Comparison: Week 49-52: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.8195% CI: [-3.78, 2.96]ANCOVA
Comparison: Week 1-4: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.65495% CI: [-1.14, 1.81]ANCOVA
Comparison: Week 5-8: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.83495% CI: [-1.84, 2.28]ANCOVA
Comparison: Week 9-12: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.74495% CI: [-2.41, 1.72]ANCOVA
Comparison: Week 13-16: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.90995% CI: [-1.7, 1.91]ANCOVA
Comparison: Week 17-20: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.96395% CI: [-1.94, 1.85]ANCOVA
Comparison: Week 21-24: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.62595% CI: [-1.77, 2.94]ANCOVA
Comparison: Week 25-28: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.94795% CI: [-2.39, 2.23]ANCOVA
Comparison: Week 29-32: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.50595% CI: [-1.25, 2.53]ANCOVA
Comparison: Week 33-36: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.56495% CI: [-1.23, 2.25]ANCOVA
Comparison: Week 37-40: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.73995% CI: [-2.21, 1.57]ANCOVA
Comparison: Week 41-44: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.76695% CI: [-2.27, 1.67]ANCOVA
Comparison: Week 45-48: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.93195% CI: [-1.92, 2.1]ANCOVA
Comparison: Week 49-52: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.91195% CI: [-3.17, 3.56]ANCOVA
Comparison: Week 1-4: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.00395% CI: [0.92, 4.3]ANCOVA
Comparison: Week 5-8: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: <0.00195% CI: [1.79, 6.58]ANCOVA
Comparison: Week 9-12: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.00595% CI: [1.03, 5.86]ANCOVA
Comparison: Week 13-16: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.00495% CI: [1.01, 5.3]ANCOVA
Comparison: Week 17-20: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.02395% CI: [0.36, 4.87]ANCOVA
Comparison: Week 21-24: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.00895% CI: [0.96, 6.54]ANCOVA
Comparison: Week 25-28: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.01295% CI: [0.78, 6.26]ANCOVA
Comparison: Week 29-32: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: <0.00195% CI: [1.55, 6.07]ANCOVA
Comparison: Week 33-36: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: <0.00195% CI: [1.68, 5.83]ANCOVA
Comparison: Week 37-40: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.00495% CI: [1.05, 5.54]ANCOVA
Comparison: Week 41-44: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.17595% CI: [-0.73, 3.99]ANCOVA
Comparison: Week 45-48: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.2795% CI: [-1.05, 3.75]ANCOVA
Comparison: Week 49-52: An ANCOVA model was used with treatment, center as factors, and baseline as the covariate.p-value: 0.07795% CI: [-0.41, 7.97]ANCOVA
Secondary
Percentage of Participants With Hyperplasia at 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.
Time frame: Month 24
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Hyperplasia at Month 24 | 0.00 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Hyperplasia at Month 24 | 4.93 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Hyperplasia at Month 24 | 0.00 percentage of participants |
| Placebo | Percentage of Participants With Hyperplasia at Month 24 | 0.00 percentage of participants |
Secondary
Percentage of Participants With Uterine Bleeding or Spotting
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 1-4 (n=330, 313, 159, 155) | 5.45 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 5-8 (n=320, 315, 153, 151) | 2.19 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 9-12 (n=316, 310, 147, 146) | 2.53 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 13-16 (n=310, 296, 137, 149) | 2.90 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 17-20 (n=315, 311, 144, 150) | 2.22 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 21-24 (n=311, 306, 142, 147) | 0.96 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 25-28 (n=294, 290, 131, 143) | 2.04 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 29-32 (n=298, 297, 135, 141) | 0.67 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 33-36 (n=296, 291, 134, 140) | 2.03 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 37-40 (n=282, 279, 131, 139) | 2.13 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 41-44 (n=285, 284, 132, 141) | 1.40 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 45-48 (n=280, 282, 130, 140) | 1.79 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 49-52 (n=45, 51, 15, 31) | 0.00 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 13-16 (n=310, 296, 137, 149) | 2.70 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 49-52 (n=45, 51, 15, 31) | 1.96 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 41-44 (n=285, 284, 132, 141) | 1.06 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 29-32 (n=298, 297, 135, 141) | 2.02 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 9-12 (n=316, 310, 147, 146) | 4.52 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 1-4 (n=330, 313, 159, 155) | 4.15 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 37-40 (n=282, 279, 131, 139) | 2.87 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 33-36 (n=296, 291, 134, 140) | 2.75 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 21-24 (n=311, 306, 142, 147) | 1.31 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 17-20 (n=315, 311, 144, 150) | 1.61 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 5-8 (n=320, 315, 153, 151) | 2.86 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 45-48 (n=280, 282, 130, 140) | 2.48 percentage of participants |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 25-28 (n=294, 290, 131, 143) | 1.38 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 41-44 (n=285, 284, 132, 141) | 8.33 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 13-16 (n=310, 296, 137, 149) | 16.79 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 17-20 (n=315, 311, 144, 150) | 16.67 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 49-52 (n=45, 51, 15, 31) | 33.33 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 21-24 (n=311, 306, 142, 147) | 16.20 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 25-28 (n=294, 290, 131, 143) | 9.92 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 45-48 (n=280, 282, 130, 140) | 11.54 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 29-32 (n=298, 297, 135, 141) | 11.11 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 33-36 (n=296, 291, 134, 140) | 11.94 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 37-40 (n=282, 279, 131, 139) | 11.45 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 1-4 (n=330, 313, 159, 155) | 19.50 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 5-8 (n=320, 315, 153, 151) | 23.53 percentage of participants |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percentage of Participants With Uterine Bleeding or Spotting | Week 9-12 (n=316, 310, 147, 146) | 25.17 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 37-40 (n=282, 279, 131, 139) | 2.88 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 29-32 (n=298, 297, 135, 141) | 0.71 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 13-16 (n=310, 296, 137, 149) | 1.34 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 1-4 (n=330, 313, 159, 155) | 4.52 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 25-28 (n=294, 290, 131, 143) | 2.10 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 21-24 (n=311, 306, 142, 147) | 2.72 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 9-12 (n=316, 310, 147, 146) | 2.74 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 5-8 (n=320, 315, 153, 151) | 3.31 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 17-20 (n=315, 311, 144, 150) | 0.67 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 33-36 (n=296, 291, 134, 140) | 2.86 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 49-52 (n=45, 51, 15, 31) | 6.45 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 45-48 (n=280, 282, 130, 140) | 2.86 percentage of participants |
| Placebo | Percentage of Participants With Uterine Bleeding or Spotting | Week 41-44 (n=285, 284, 132, 141) | 2.84 percentage of participants |
Comparison: Week 41-44: The Fisher exact test was used for comparisons between groups.p-value: 0.062Fisher Exact
Comparison: Week 1-4: The Fisher exact test was used for comparisons between groups.p-value: 0.826Fisher Exact
Comparison: Week 5-8: The Fisher exact test was used for comparisons between groups.p-value: 0.534Fisher Exact
Comparison: Week 9-12: The Fisher exact test was used for comparisons between groups.p-value: 1Fisher Exact
Comparison: Week 13-16: The Fisher exact test was used for comparisons between groups.p-value: 0.516Fisher Exact
Comparison: Week 17-20: The Fisher exact test was used for comparisons between groups.p-value: 0.446Fisher Exact
Comparison: Week 21-24: The Fisher exact test was used for comparisons between groups.p-value: 0.218Fisher Exact
Comparison: Week 25-28: The Fisher exact test was used for comparisons between groups.p-value: 1Fisher 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: 0.733Fisher Exact
Comparison: Week 37-40: The Fisher exact test was used for comparisons between groups.p-value: 0.736Fisher Exact
Comparison: Week 41-44: The Fisher exact test was used for comparisons between groups.p-value: 0.449Fisher Exact
Comparison: Week 45-48: The Fisher exact test was used for comparisons between groups.p-value: 0.489Fisher Exact
Comparison: Week 49-52: The Fisher exact test was used for comparisons between groups.p-value: 0.163Fisher Exact
Comparison: Week 1-4: The Fisher exact test was used for comparisons between groups.p-value: 0.813Fisher Exact
Comparison: Week 5-8: The Fisher exact test was used for comparisons between groups.p-value: 0.777Fisher Exact
Comparison: Week 9-12: The Fisher exact test was used for comparisons between groups.p-value: 0.448Fisher Exact
Comparison: Week 13-16: The Fisher exact test was used for comparisons between groups.p-value: 0.507Fisher Exact
Comparison: Week 17-20: The Fisher exact test was used for comparisons between groups.p-value: 0.669Fisher Exact
Comparison: Week 21-24: The Fisher exact test was used for comparisons between groups.p-value: 0.281Fisher Exact
Comparison: Week 25-28: The Fisher exact test was used for comparisons between groups.p-value: 0.689Fisher Exact
Comparison: Week 29-32: The Fisher exact test was used for comparisons between groups.p-value: 0.437Fisher Exact
Comparison: Week 33-36: The Fisher exact test was used for comparisons between groups.p-value: 1Fisher Exact
Comparison: Week 37-40: The Fisher exact test was used for comparisons between groups.p-value: 1Fisher Exact
Comparison: Week 41-44: The Fisher exact test was used for comparisons between groups.p-value: 0.227Fisher Exact
Comparison: Week 45-48: The Fisher exact test was used for comparisons between groups.p-value: 0.758Fisher Exact
Comparison: Week 49-52: The Fisher exact test was used for comparisons between groups.p-value: 0.554Fisher 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: 0.008Fisher 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: 0.005Fisher Exact
Comparison: Week 37-40: The Fisher exact test was used for comparisons between groups.p-value: 0.008Fisher Exact
Comparison: Week 45-48: The Fisher exact test was used for comparisons between groups.p-value: 0.007Fisher Exact
Comparison: Week 49-52: The Fisher exact test was used for comparisons between groups.p-value: 0.029Fisher Exact
Secondary
Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at 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.
Time frame: Baseline, Month 24
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 24 | 0.96 percent change | Standard Error 0.4 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 24 | 0.86 percent change | Standard Error 0.41 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 24 | 2.39 percent change | Standard Error 0.57 |
| Placebo | Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 24 | -2.29 percent change | Standard Error 0.57 |
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [1.92, 4.58]ANCOVA
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [1.83, 4.46]ANCOVA
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [3.13, 6.23]ANCOVA
Secondary
Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at 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.
Time frame: Baseline, Month 24
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Bazedoxifene 20 mg/Conjugated Estrogen 0.45 mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 24 | 0.30 percent change | Standard Error 0.31 |
| Bazedoxifene 20 mg/Conjugated Estrogen 0.625 mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 24 | 0.41 percent change | Standard Error 0.32 |
| Conjugated Estrogen 0.45 mg/Medroxyprogesterone Acetate 1.5mg | Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 24 | 0.85 percent change | Standard Error 0.44 |
| Placebo | Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 24 | -1.53 percent change | Standard Error 0.45 |
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [0.8, 2.87]ANCOVA
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [0.92, 2.97]ANCOVA
Comparison: An ANCOVA model was used with treatment and center as main effects and baseline BMD and years since menopause as covariates.p-value: <0.00195% CI: [1.17, 3.59]ANCOVA