Reduction of new vertebral fractures in osteoporotic postmenopausal women- Osteoporosis MedDRA version: 9.1 Level: LLT Classification code 10031282 Term: Osteoporosis
Conditions
Interventions
Product Name: TSE-424 (bazedoxifene acetate)
Product Code: TSE-424
Pharmaceutical Form: Capsule*
INN or Proposed INN: TSE-424 (bazedoxifene acetate)
CAS Number: 198481-33-3
Current Sponsor code: TSE-4
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria in the Core Study 1. Generally healthy postmenopausal women · from 55 to 85 years of age in non-US countries · from 55 to 80 years of age in US only. 2. Subjects must be at least 2 years postmenopausal defined by any of the following: a. Last natural menstrual cycle at least 2 years before screening; or, b. Subject is over 60 years of age; or, c. Surgical menopause (bilateral oophorectomy with or without hysterectomy) at least 2 years before screening. 3. a. Osteoporotic subjects without vertebral fracture: · In non-US countries: BMD T-score at the femoral neck or lumbar spine of –2.5 or worse without the presence of a vertebral fracture. · In US only BMD T-score at the femoral neck or lumbar spine between –2.5 and –4.0 (inclusive) without the presence of a vertebral fracture. or b. Osteoporotic subjects with vertebral fracture: · In non-US countries: the presence of 1 to 5 mild or moderate asymptomatic vertebral fracture(s) and a lumbar spine and femoral neck BMD T-score not worse than –3.5. · In US only: the presence of 1 mild asymptomatic vertebral fracture and a lumbar spine and femoral neck BMD T-score not worse than -4.0. 4. In the opinion of the investigator, the subject will be compliant and have a high probability of completing the study. 5. Subjects must sign and date a written Institutional Review Board–approved informed consent before any screening procedures are performed. 6. Subjects in the Endometrial Safety Substudy must have a uterus accessible to endometrial sampling. 7. Subjects participating in the Electrocardiogram Substudy must have an original copy of the baseline ECG available for comparison. Inclusion Criteria in the Study Extension I 1. Completion of the Core Study. 2. In the opinion of the investigator, the subject will be compliant and have a high probability of completing the Study Extension. 3. Subjects must sign and date a written Institutional Review Board IRB) /Independent Ethics Committee (IEC) - approved informed consent, before any Study Extension procedures are performed. Inclusion Criteria in the Study Extension II: 1. Completion of the Study Extension I. 2. In the opinion of the investigator, the subject will be compliant and have a high probability of completing the Study Extension II. 3. Subjects must sign and date a written Institutional Review Board (IRB)/Independent Ethics Committee (IEC) - approved informed consent, before any Study Extension II procedures are performed Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Core Study: 1. Diseases that may affect bone metabolism (e.g., hypercalcemia, hypocalcemia, osteogenesis imperfecta, chronic gastrointestinal disease, Paget’s disease or hyperparathyroidism). 2. Women from whom satisfactory thoracic & lumbar spine radiographs cannot be obtained, or with fewer than 4thoracic & 2lumbar vertebrae that are evaluable. 3. Non-US countries: women with more than 5mild or moderate prevalent vertebral fractures. US only, women with more than 1 mild prevalent vertebral fracture. 4. Non-US countries: women with 1 or more severe prevalent vertebral fracture(s). US only: women with 1 or more moderate or severe prevalent vertebral fracture(s). 5. US only, women with vertebral or hip fractures known or suspected to have occurred within 2years of baseline. 6. Any conditions that can substantially interfere with obtaining lumbar spine BMD (e.g., degenerative diseases of the spine, severe scoliosis). 7. In non-hysterectomized women, known history of or suspected endometrial hyperplasia or carcinoma. For subjects in the Endometrial Safety Substudy, endometrial thickness at baseline greater than 5mm (double-wall, fluid excluded) as measured by transvaginal ultrasonography or endometrial hyperplasia or carcinoma (as determined by either of the 2 pathologists) at the baseline biopsy. 8. Abnormal vaginal bleeding at baseline. 9. Vasomotor symptoms requiring treatment. 10. Pathologic vertebral fractures. 11. Known history or suspected cancer of the breast. 12. Unresolved cervical cytology smear report of atypical glandular cells of undetermined significance, atypical squamous cells of undetermined significance favoring low-grade squamous intraepithelial lesions, or low-grade squamous intraepithelial lesions or higher. 13. Malignancy, or treatment for malignancy, within the previous 10years. A history or active presence of basal cell carcinoma of the skin does not exclude the subject. 14. Active or past history of venous thromboembolic events, including DVT, pulmonary embolism, or retinal vein thrombosis. 15. A BMI above 35. 16. Elevated sitting (after 5minutes) blood pressure (180mmHg systolic or 90mmHg diastolic). 17. Aspartate aminotransferase &/or alanine aminotransferase @1.5 times the upper limit of normal for the laboratory used. 18. Serum creatinine @2 times the upper limit of normal for the laboratory used. 19. Active renal lithiasis 20. Alkaline phosphatase @2 times the upper limit of normal for the laboratory used. 21. Total bilirubin @1.5 times the upper limit of normal for the laboratory used. Subjects with a preexisting diagnosis of Gilbert’s syndrome may be included after approval by the medical monitor. 22. Fasting total cholesterol >8.00mmol/L (310mg/dL) or triglycerides >3.40mmol/L (300mg/dL). 23. Endocrine disorders requiring treatment (except well-controlled Type II diabetes mellitus or hypothyroidism). 24. Untreated malabsorption disorders. 25. In the opinion of the investigator, any serious underlying disease or clinically significant abnormal physical finding precluding subject participation in a 3year study. 26. Use of the following drugs within 6months of screening:Systemic estrogen (except estriol 2mg/d);Topical estrogen more often than 3times a week; Progestogens; &rogens;Calcitonin; Bisphosphonates;Parathyroid hormone; SERMs; Cholecalciferol (more than 50,000IU a week);Antiseizure drugs 27. Systemic fluoride treatment (other than topical dental) for more than 1 month within 6months before screeni
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of bazedoxifene acetate 20 mg and bazedoxifene acetate 40 mg in comparison to placebo in reduction of new vertebral fractures in osteoporotic postmenopausal women after 36 months and after 60 months of therapy and after 84 months of therapy. To compare the safety profile of bazedoxifene acetate to placebo.;Secondary Objective: Compare bazedoxifene acetate to placebo & raloxifene after 36months on: breast cancer incidence; clinical vertebral fractures; worsening vertebral fractures; nonvertebral fractures; height changes; Bone Mineral Density of lumbar spine & hip; serum bone markers; the impact on lipid parameters & quality of life; endometrial assessment (substudy[ss]); bone histomorphometry (ss); the effect on cardiac repolarization (electrocardiogram ss). A comparison of raloxifene 60mg to placebo in reducing the incidence of new vertebral fractures & other fractures after 36months of treatment will also be conducted. Compare bazedoxifene acetate to placebo after 60months & 84months of therapy on: breast cancer incidence; clinical vertebral fractures; worsening verterbral fractures; nonvertebral fractures; height changes; Bone Mineral Density (BMD) of lumbar spine & hip; endometrial assessment (ss); serum bone markers (ss); bone histomorphometry (substudy II only);Primary end point(s): The primary endpoint of interest is reduction in the incidence of new vertebral fractures | — |
Countries
Bulgaria, Hungary
Outcome results
None listed