Risedronate vs Raloxifene in Hormone Replacement Therapy Discontinuation

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind, double-dummy study designed to compare the effects of risedronate, raloxifene, and placebo on BMD, bone turnover markers, and other markers of anabolic activity in postmenopausal women who previously received HRT.

Official Title
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An 18-Month, Multicenter, Parallel-Group Study to Determine The Relative Efficacy of Risedronate Versus Raloxifene in Subjects Who Have Discontinued Hormone Replacement Therapy (HRT) for Early Intervention in Osteoporosis

Conditions
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Osteoporosis, Postmenopausal

Intervention / Treatment
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* Drug: Risedronate
* Drug: Raloxifene
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal, ambulatory females, postmenopausal defined as the absence of menses for at least 12 continuous months) In general good health as determined by medical history, physical examination, and laboratory tests LS spine BMD T-score between -1.0 and -2.4, inclusive At least one analyzable BMD site at both the hip (left or right) and LS spine (at least 3 measurable lumbar spine vertebrae, without fracture or sufficient degenerative disease) Currently receiving no medications for the treatment or prevention of osteoporosis Had been on continuous HRT for at least 1 year prior to enrollment. The HRT must have ended within 18 months prior to the baseline visit, and the subject must have been off HRT medication for at least 3 months at the time of baseline visit Subjects rendered menopausal by surgical procedures between the ages of 55 and 65 years Exclusion Criteria: A history of cancer within 10 years prior to entry into the study, except for relatively benign and cured skin cancers such as basal and squamous cell carcinoma A history of hyperparathyroidism, hyperthyroidism, osteomalacia, or other metabolic bone disease within one year prior to enrollment Any condition or disease that may interfere with the evaluation of at least 3 lumbar vertebrae (not necessarily contiguous), determined in a screening radiograph by a radiologist at the central facility (e.g., confluent aortic calcifications, severe osteoarthritis, spinal fusion, lumbar spine fractures) Evidence of clinically significant organic or psychiatric disease on history or physical examination, which in the opinion of the investigator would prevent the patient from completing the study Markedly abnormal pretreatment laboratory finds that, in the opinion of the investigator, would prevent the patient from completing the study A history of using any of the following medications prior to starting study: Any bisphosphonate therapy Selective estrogen receptor modulators (SERMs) Parathyroid hormone Fluorides Calcitonin Calcitriol (>1.5 mcg/week) Corticosteroids on a chronic basis for period equal to or greater then 3 months Received a depot injection of >10,000 IU Vitamin D in the past 12 months A history of recurrent nephrolithiasis or a history of one episode of nephrolithiasis within 1 year of study entry Serum creatinine >1.6 mg/dl Unable to sit or stand upright for 30 minutes after taking the morning dose of risedronate A history of deep vein thrombosis or other coagulation disorders Severe hepatic insufficiency A history of hypersensitivity to raloxifene, risedronate, or to drugs with similar chemical structures Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult Subjects found to have one or more vertebral fractures after completing thoracic and LS spine films Subjects who have experienced a low impact fracture related to osteopenia within two years of baseline visit The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Ages Eligible for Study
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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>Risedronate 35mg once a week | Drug: Risedronate<br> <br> |
| Active Comparator: 2<br>Raloxifene 60mg daily | Drug: Raloxifene<br> <br> |
| Placebo Comparator: 3<br> | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effects of risedronate and raloxifene on lumbar spine (LS) bone mineral density (BMD) in osteopenic women previously treated with HRT, who discontinued HRT at least 3 months prior to the study but no greater than 18 mos |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effects of risedronate, raloxifene, and placebo on BMD of the hip |  |  |