Study Evaluating Bazedoxifene/Conjugated Estrogens Combinations In Postmenopausal Women

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

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.

Study Overview

• Status: Completed
• Conditions: Endometrial Hyperplasia; Osteoporosis
• Intervention / Treatment: Drug: Bazedoxifene/Conjugated Estrogen; Drug: CE 0.45 mg/MPA 1.5mg; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1083
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Upland, California, United States, 91786
      • Pfizer Investigational Site
  • Florida
    • Inverness, Florida, United States, 34452
      • Pfizer Investigational Site
    • West Palm Beach, Florida, United States, 33409
      • Pfizer Investigational Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Pfizer Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Pfizer Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
      • Pfizer Investigational Site
  • Montana
    • Billings, Montana, United States, 59102
      • Pfizer Investigational Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Pfizer Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (ACTUAL): September 1, 2008
• Study Completion (ACTUAL): September 1, 2008

Study Registration Dates

• First Submitted: October 18, 2005
• First Submitted That Met QC Criteria: October 19, 2005
• First Posted (ESTIMATE): October 20, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): December 20, 2013
• Last Update Submitted That Met QC Criteria: October 30, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Menopause; Endometrium; Uterus
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Uterine Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Hyperplasia; Endometrial Hyperplasia; Osteoporosis; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bazedoxifene; Estrogens; Estrogens, Conjugated (USP)
• Other Study ID Numbers: 3115A1-304