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

Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00808132
• Other study ID #: 3115A1-3307
• Secondary ID: B2311009
• Status: Completed
• Phase: Phase 3
• First received: December 12, 2008
• Last updated: March 10, 2014
• Start date: January 2009
• Est. completion date: February 2011

Study information

• Verified date: March 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1886
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years to 64 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Menopause
• Osteoporosis
• Osteoporosis, Postmenopausal

Intervention

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

Locations

Country	Name	City	State
Argentina	Pfizer Investigational Site	Buenos Aires
Argentina	Pfizer Investigational Site	Buenos Aires
Argentina	Pfizer Investigational Site	Caba	Buenos Aires
Argentina	Pfizer Investigational Site	Caba	Buenos Aires
Australia	Pfizer Investigational Site	Perth	Western Australia
Australia	Pfizer Investigational Site	Randwick	New South Wales
Australia	Pfizer Investigational Site	St Leonards	New South Wales
Chile	Pfizer Investigational Site	Santiago	RM
Colombia	Pfizer Investigational Site	Barranquilla	Atlantico
Colombia	Pfizer Investigational Site	Bogota	Cundinamarca
Colombia	Pfizer Investigational Site	Medellin	Antioquia
Denmark	Pfizer Investigational Site	Aalborg
Denmark	Pfizer Investigational Site	Ballerup
Denmark	Pfizer Investigational Site	Vejle
Finland	Pfizer Investigational Site	Kuopio
Finland	Pfizer Investigational Site	Oulu
Hungary	Pfizer Investigational Site	Bekescsaba
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Debrecen
Hungary	Pfizer Investigational Site	Debrecen
Hungary	Pfizer Investigational Site	Kecskemet
Hungary	Pfizer Investigational Site	Nyiregyhaza
Hungary	Pfizer Investigational Site	Tatabanya
Mexico	Pfizer Investigational Site	D.F
New Zealand	Pfizer Investigational Site	Christchurch
New Zealand	Pfizer Investigational Site	Dunedin	NZ
New Zealand	Pfizer Investigational Site	Wellington	NZ
Norway	Pfizer Investigational Site	Alesund
Norway	Pfizer Investigational Site	Hamar
Poland	Pfizer Investigational Site	Lublin
Poland	Pfizer Investigational Site	Poznan
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Wroclaw
United States	Pfizer Investigational Site	Akron	Ohio
United States	Pfizer Investigational Site	Albuquerque	New Mexico
United States	Pfizer Investigational Site	Albuquerque	New Mexico
United States	Pfizer Investigational Site	Ann Arbor	Michigan
United States	Pfizer Investigational Site	Atlanta	Georgia
United States	Pfizer Investigational Site	Augusta	Georgia
United States	Pfizer Investigational Site	Bangor	Maine
United States	Pfizer Investigational Site	Billings	Montana
United States	Pfizer Investigational Site	Billings	Montana
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Bismarck	North Dakota
United States	Pfizer Investigational Site	Bluffton	South Carolina
United States	Pfizer Investigational Site	Boise	Idaho
United States	Pfizer Investigational Site	Boynton Beach	Florida
United States	Pfizer Investigational Site	Brick	New Jersey
United States	Pfizer Investigational Site	Brooklyn Center	Minnesota
United States	Pfizer Investigational Site	Carmichael	California
United States	Pfizer Investigational Site	Chandler	Arizona
United States	Pfizer Investigational Site	Charlotte	North Carolina
United States	Pfizer Investigational Site	Charlottesville	Virginia
United States	Pfizer Investigational Site	Chaska	Minnesota
United States	Pfizer Investigational Site	Chattanooga	Tennessee
United States	Pfizer Investigational Site	Chicago	Illinois
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Clearwater	Florida
United States	Pfizer Investigational Site	Cleveland	Ohio
United States	Pfizer Investigational Site	Cleveland	Ohio
United States	Pfizer Investigational Site	Colorado Springs	Colorado
United States	Pfizer Investigational Site	Colorado Springs	Colorado
United States	Pfizer Investigational Site	Columbus	Ohio
United States	Pfizer Investigational Site	Corpus Christi	Texas
United States	Pfizer Investigational Site	Crystal River	Florida
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dayton	Ohio
United States	Pfizer Investigational Site	Daytona Beach	Florida
United States	Pfizer Investigational Site	Decatur	Georgia
United States	Pfizer Investigational Site	Decatur	Georgia
United States	Pfizer Investigational Site	Deland	Florida
United States	Pfizer Investigational Site	Denton	Texas
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Englewood	Ohio
United States	Pfizer Investigational Site	Erie	Pennsylvania
United States	Pfizer Investigational Site	Eugene	Oregon
United States	Pfizer Investigational Site	Fargo	North Dakota
United States	Pfizer Investigational Site	Fort Worth	Texas
United States	Pfizer Investigational Site	Ft. Lauderdale	Florida
United States	Pfizer Investigational Site	Ft. Lauderdale	Florida
United States	Pfizer Investigational Site	Ft. Myers	Florida
United States	Pfizer Investigational Site	Glendale	Arizona
United States	Pfizer Investigational Site	Greer	South Carolina
United States	Pfizer Investigational Site	Hilton Head Island	South Carolina
United States	Pfizer Investigational Site	Hopwood	Pennsylvania
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Idaho Falls	Idaho
United States	Pfizer Investigational Site	Irving	Texas
United States	Pfizer Investigational Site	Irving	Texas
United States	Pfizer Investigational Site	Jackson	Tennessee
United States	Pfizer Investigational Site	Jenkintown	Pennsylvania
United States	Pfizer Investigational Site	Johnstown	Pennsylvania
United States	Pfizer Investigational Site	Kalamazoo	Michigan
United States	Pfizer Investigational Site	Kernersville	North Carolina
United States	Pfizer Investigational Site	Knoxville	Tennessee
United States	Pfizer Investigational Site	Lake Worth	Florida
United States	Pfizer Investigational Site	Lakewood	Colorado
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	Lebanon	New Hampshire
United States	Pfizer Investigational Site	Lexington	Kentucky
United States	Pfizer Investigational Site	Lincoln	Nebraska
United States	Pfizer Investigational Site	Little Rock	Arkansas
United States	Pfizer Investigational Site	Lousiville	Kentucky
United States	Pfizer Investigational Site	Mayfield Heights	Ohio
United States	Pfizer Investigational Site	Medford	Oregon
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	Meridian	Idaho
United States	Pfizer Investigational Site	Mesa	Arizona
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Miami Springs	Florida
United States	Pfizer Investigational Site	Minot	North Dakota
United States	Pfizer Investigational Site	Mobile	Alabama
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	New Brunswick	New Jersey
United States	Pfizer Investigational Site	New London	Connecticut
United States	Pfizer Investigational Site	New Port Richey	Florida
United States	Pfizer Investigational Site	New York	New York
United States	Pfizer Investigational Site	Norfolk	Virginia
United States	Pfizer Investigational Site	Norfolk	Virginia
United States	Pfizer Investigational Site	North Las Vegas	Nevada
United States	Pfizer Investigational Site	Omaha	Nebraska
United States	Pfizer Investigational Site	Overland Park	Kansas
United States	Pfizer Investigational Site	Paw Paw	Michigan
United States	Pfizer Investigational Site	Peoria	Arizona
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Phoenix	Arizona
United States	Pfizer Investigational Site	Pinellas Park	Florida
United States	Pfizer Investigational Site	Pittsburgh	Pennsylvania
United States	Pfizer Investigational Site	Plano	Texas
United States	Pfizer Investigational Site	Pleasant Grove	Utah
United States	Pfizer Investigational Site	Port Jefferson	New York
United States	Pfizer Investigational Site	Portland	Oregon
United States	Pfizer Investigational Site	Reno	Nevada
United States	Pfizer Investigational Site	Richmond	Virginia
United States	Pfizer Investigational Site	Robbinsdale	Minnesota
United States	Pfizer Investigational Site	Rockford	Illinois
United States	Pfizer Investigational Site	Sacramento	California
United States	Pfizer Investigational Site	Saginaw	Michigan
United States	Pfizer Investigational Site	Salt Lake City	Utah
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	Sandy	Utah
United States	Pfizer Investigational Site	Savannah	Georgia
United States	Pfizer Investigational Site	Savannah	Georgia
United States	Pfizer Investigational Site	Scottsdale	Arizona
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	Sioux Falls	South Dakota
United States	Pfizer Investigational Site	Sioux Falls	South Dakota
United States	Pfizer Investigational Site	Sioux Falls	South Dakota
United States	Pfizer Investigational Site	South Bend	Indiana
United States	Pfizer Investigational Site	Southfield	Michigan
United States	Pfizer Investigational Site	St Louis	Missouri
United States	Pfizer Investigational Site	Sunrise	Florida
United States	Pfizer Investigational Site	Tacoma	Washington
United States	Pfizer Investigational Site	Tampa	Florida
United States	Pfizer Investigational Site	Tucson	Arizona
United States	Pfizer Investigational Site	Tucson	Arizona
United States	Pfizer Investigational Site	Tucson	Arizona
United States	Pfizer Investigational Site	Upland	California
United States	Pfizer Investigational Site	Vero Beach	Florida
United States	Pfizer Investigational Site	Vista	California
United States	Pfizer Investigational Site	Waco	Texas
United States	Pfizer Investigational Site	Walnut Creek	California
United States	Pfizer Investigational Site	Warwick	Rhode Island
United States	Pfizer Investigational Site	Watertown	South Dakota
United States	Pfizer Investigational Site	West Reading	Pennsylvania
United States	Pfizer Investigational Site	Wexford	Pennsylvania
United States	Pfizer Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Breast Tenderness	Percentage of participants who reported at least 1 day of breast tenderness during each 4-week period for 1-year on therapy was calculated.	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	No
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.	Month 12	Yes
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.	Baseline, Month 12	No
Secondary	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Month 6: Osteoporosis Sub-Study	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.	Baseline, Month 6	No
Secondary	Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Month 6, 12: Osteoporosis Sub-Study	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.	Baseline, Month 6, Month 12	No
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.	Day 1 up to Day 364	No
Secondary	Percent Change From Baseline in Breast Density at Month 12: Breast Density Sub-Study	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	Baseline, Month 12	No
Secondary	Percent Change From Baseline in Bone Turnover Markers (BTMs) at Month 6 and Month 12: Osteoporosis Sub-Study	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.	Baseline, Month 6, 12	No
Secondary	Medical Outcomes Study (MOS) Sleep Scale at Baseline: 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.	Baseline	No
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.	Baseline, Month 3	No
Secondary	Menopause-Specific Quality of Life (MENQOL) Score at Baseline: 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.	Baseline	No
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.	Baseline, Month 3	No
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.	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	No

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