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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00808132
First received: December 12, 2008
Last updated: March 10, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Menopause
Osteoporosis
Drug: bazedoxifene 20 mg/ conjugated estrogens 0.45 mg
Drug: bazedoxifene 20 mg/ conjugated estrogens 0.625 mg
Drug: bazedoxifene 20 mg
Drug: conjugated estrogens 0.45 mg/ medroxyprogesterone acetate 1.5 mg
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants With Endometrial Hyperplasia at Month 12: Main Study [ Time Frame: Month 12 ] [ Designated as safety issue: Yes ]
    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.

  • Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 12: Osteoporosis Sub-Study [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 6: Osteoporosis Sub-Study [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 6, 12: Osteoporosis Sub-Study [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to Day 364 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 6, 12 ] [ Designated as safety issue: No ]
    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.

  • Medical Outcomes Study (MOS) Sleep Scale at Baseline: Sleep Sub-Study [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Medical Outcomes Study (MOS) Sleep Scale at Month 3: Sleep Sub-Study [ Time Frame: Baseline, Month 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 3 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    Percentage of participants with uterine bleeding were calculated for each 4-week period for 1-year on therapy.


Other Outcome Measures:
  • Percentage of Participants With Breast Tenderness [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Percentage of participants who reported at least 1 day of breast tenderness during each 4-week period for 1-year on therapy was calculated.


Enrollment: 1886
Study Start Date: January 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
bazedoxifene 20 mg/conjugated estrogens 0.45 mg
Drug: bazedoxifene 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.
Experimental: 2
bazedoxifene 20 mg/conjugated estrogens 0.625 mg
Drug: bazedoxifene 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.
Experimental: 3
bazedoxifene 20 mg
Drug: bazedoxifene 20 mg
One capsule, bazedoxifene 20 mg (over-encapsulated), once a day for one year.
Active Comparator: 4
Prempro
Drug: conjugated 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.
Other Name: Prempro
Placebo Comparator: 5
Placebo
Drug: Placebo
One capsule, placebo (over-encapsulated), once a day for one year.

  Eligibility

Ages Eligible for Study:   40 Years to 64 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00808132

  Show 178 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00808132     History of Changes
Other Study ID Numbers: 3115A1-3307, B2311009
Study First Received: December 12, 2008
Results First Received: October 30, 2013
Last Updated: March 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Postmenopausal Women
Bazedoxifene/Conjugated Estrogens

Additional relevant MeSH terms:
Endometrial Hyperplasia
Osteoporosis
Osteoporosis, Postmenopausal
Uterine Diseases
Genital Diseases, Female
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Estrogens, Conjugated (USP)
Estrogens
Medroxyprogesterone
Medroxyprogesterone Acetate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Male
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2014