Comparison of Raloxifene Hydrochloride and Placebo in the Treatment of Postmenopausal Women With Osteoporosis

Condition(s) targeted: Osteoporosis, Postmenopausal

Intervention: Raloxifene HCL (Drug); Raloxifene HCL (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Eli Lilly and Company

Official(s) and/or principal investigator(s):
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study Director, Affiliation: Eli Lilly and Company

To study the effect of long-term treatment with raloxifene, compared with placebo, on the rate of new vertebral fractures in osteoporotic postmenopausal women with and without existing vertebral fractures.

Official title: Comparison of Raloxifene Hydrochloride and Placebo in the Treatment of Postmenopausal Women With Osteoporosis

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

To establish the effect of long-term treatment with raloxifene, compared with placebo, on the rate of new vertebral fractures in osteoporotic postmenopausal women with and without prevalent vertebral fractures by spinal x-ray.

To establish the effect of long-term treatment with raloxifene, compared with placebo, on lumbar spine and femoral neck bone mineral density (BMD) in postmenopausal women with osteoporosis.

To establish the safety of chronic administration of raloxifene in postmenopausal women with osteoporosis. Adverse events (AEs), physical exam (PE), EKG, mammograms and laboratory tests will be used to assess safety in the patients.

Secondary outcome:

To establish the effect of long-term treatment with raloxifene, compared with placebo, on total body bone mineral content and radial BMD in postmenopausal women with osteoporosis.

To establish the effect of raloxifene, compared with placebo, on the rates of new nonvertebral fractures alone & of nonvertebral & vertebral fractures combined in postmenopausal women with osteoporosis by spinal x-ray & assessment of clinical fractures.

To establish the effect of long-term treatment with raloxifene, compared with placebo, on biochemical markers of bone metabolism in postmenopausal women with osteoporosis.

To establish the effect of long-term treatment with raloxifene, compared with placebo, on serum lipids and other laboratory markers of cardiovascular risk in postmenopausal women with osteoporosis.

To quantify medical resources utilized by patients treated with raloxifene so that a subsequent incremental cost-effectiveness analysis can be performed by quantifying overnight hospitalizations or osteoporotic fractures.

To assess the impact of raloxifene on quality of life in osteoporotic women with prevalent vertebral fractures by the completion of Quality of Life instruments.

To assess the impact of raloxifene on cognitive & neuropsychomotor function using a standardized battery of neuropsychometric tests.

To assess the impact of treatment with raloxifene on risk of cardiovascular disease by monitoring biochemical markers of cardiovascular risk.

To assess the possible impact of long-term treatment with raloxifene on risks of endometrial cancer by pelvic gynecological exams and by use of uterine ultrasound in a subset of patients.

To assess the possible impact of long-term treatment with raloxifene on breast cancer.

To determine the effect of treatment with raloxifene on the prevalence of Alzheimer's disease (AD) on subjects by using a Dementia Diagnostic Evaluation which includes a battery of tests and interviews with the patient as well as brain CT or MRI scan.

To determine the effect of long-term treatment with raloxifene on the prevalence of dementia associated with cerebrovascular (CV) disease in postmenopausal women with osteoporosis by administration of the dementia diagnosis.

Determine the effect of raloxifene on the prevalence of all causes of dementia in subjects by using a Dementia Diagnostic Evaluation which includes a battery of tests and interviews with the patient as well as brain CT or MRI scan.

Minimum age: N/A. Maximum age: 80 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Ambulatory postmenopausal women free of severe or chronically disabling conditions,

have a life expectancy of at least 5 years, be expected to remain ambulatory throughout the entire study, and be expected to return for follow-up visits.

- Women who have had their last menstrual period at least 2 years before beginning the

study.

- Women who have no language barrier, are cooperative, and who give informed consent

before entering the study

- Substudy 1: Femoral neck or lumbar spine BMD measurements 2. 5 or more standard

deviations below normal peak bone mass for healthy, premenopausal women (T-score greater then or equal to 2. 5).

- Substudy 2: Either at least one moderate or at least two mild vertebral fractures in

the presence of low BMD (as specified above) or at least two moderate vertebral fractures, regardless of BMD.

Exclusion Criteria:

- Patients with known current bone disorders other than primary osteoporosis, such as

hyperparathyroidism, Paget's disease, renal osteodystrophy, or osteomalacia

- Patients experiencing clinically severe postmenopausal symptoms at the beginning of

the study that require estrogen-replacement therapy

- Patients with known, suspected, or history of carcinoma of the breast or

estrogen-dependent neoplasia

- Patients who have had any history of cancer within the previous 5 years

- Patients with abnormal uterine bleeding

- Patients with a history of deep venous thrombosis, thromboembolic disorders, or

cerebral vascular accident within the past 10 years except for patients with a history of deep venous thrombosis due to accidents

- Patients who have endocrine disorders requiring pharmacologic therapy except for type

II diabetes

- Patients who are not biochemically euthyroid or who have had changes in thyroid

replacement therapy in the 2 months before the start of the study.

- Patients with acute or chronic liver disease

- Patients who have impaired kidney function

- Patients with active renal lithiasis

- Patients with known, severe untreated malabsorption syndromes

- Patients with pathologic fractures (both substudies) or patients in Substudy II all of

whose vertebral fractures are clearly a result of automobile accidents or other severely traumatic accidents

- Patients in whom satisfactory baseline thoracic and lumbar x-ray views cannot be

obtained

- Patients with less than two lumbar and less than four thoracic vertebrae that are

unfractured and evaluable for incident fractures

- Treatment with therapeutic doses of any of the following medications more recently

than 6 months before beginning the study: Androgen, Calcitonin, Estrogen, Progestin

- Treatment with therapeutic doses of systemic corticosteroids for more than 1 month

during the 12 months before beginning the study.

- Patients who have received therapeutic doses of fluorides

- Patients who have received bisphosphonate therapy for more than 14 days during the

past 18 months or who have received any bisphosphonate therapy within the last 6 months before beginning the study.

- Patients requiring high-dose heparinization (>7500 U/day) at study entry for a total

period of time that will presumably exceed 6 months

- Patients being treated with 50,000 IU or more of vitamin D once weekly more recently

than 3 months before beginning the study will be excluded.

- Current systemic treatment with any of the following medications at the beginning of

the study: Lithium, Anticonvulsants, regular use of phosphate-binding antacids.

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Ciudad De Buenos Aires, Argentina

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Starting date: November 1994
Ending date: September 1999
Last updated: April 30, 2008