Study Evaluating Bazedoxifene/Conjugated Estrogens Combinations In Postmenopausal Women

Study Overview
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Brief Summary
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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.

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

Conditions
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Endometrial Hyperplasia, Osteoporosis

Intervention / Treatment
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* Drug: Bazedoxifene/Conjugated Estrogen
* Drug: Bazedoxifene/Conjugated Estrogen
* Drug: CE 0.45 mg/MPA 1.5mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Screening | 
| 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. | Month 12 | 
| 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. | Screening | 
| 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. | Baseline, Month 12 | 
| 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. | Screening | 
| 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. | Baseline, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 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. | 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 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. | Month 24 | 
| 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. | Baseline, Month 24 | 
| 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. | Baseline, Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometrium, Uterus, Menopause