A Study of Arzoxifene to Treat Korean Women With Osteoporosis

Study Overview
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Brief Summary
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The study is for Korean women who are postmenopausal and also suffer from osteoporosis. The study will test if women who are given 20 mg of arzoxifene once a day for six months have a less severe level of osteoporosis than those women who do not take arzoxifene. All patients will receive 500 mg of elemental calcium and 400 to 600 IU Vitamin D daily starting 4 weeks prior to study drug administration continuing through the 6 months of therapy.

Official Title
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Effects of Arzoxifene on Bone Mineral Density in Korean Postmenopausal Women With Osteoporosis

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: arzoxifene
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Present with osteoporosis based on total hip, femoral neck or lumbar spine BMD T-score of less than or equal to -2.5 but must never have had any osteoporotic fragility fracture. Are ambulatory and are 60 to 85 years of age, inclusive. Aside from diagnosed osteoporosis (Inclusion Criterion [1]), all women must be free of severe or chronically disabling conditions, have a life expectancy of at least 5 years in the opinion of the investigator, be expected to remain ambulatory throughout the entire study, and be expected to return for follow-up visits. Had their last natural menstrual period at least 2 years before beginning the study. Are able to comprehend the requirements and procedures for the study and to provide informed consent before entering the study. Have at least two lumbar vertebrae (L1 to L4) that are evaluable via dual energy X-ray absorptiometry (DXA) and lateral thoracic and lumbar spine x-ray films that can be adequately evaluated for existing vertebral fractures at screening. Have centrally read total hip, femoral neck or lumbar spine T-score less than or equal to -2.5 Exclusion Criteria: Have known current metabolic bone disorders other than low bone mass, such as hyperparathyroidism, renal osteodystrophy, or osteomalacia. Have known, suspected, or history of carcinoma of the breast or estrogen-dependent neoplasia (e.g., endometrial or uterine carcinoma), except for hysterectomized patients with a history of carcinoma in situ of the uterus. For other cancers, be disease free and in remission from all other cancers for 5 or more years, except for excised superficial lesions, such as basal cell carcinoma or squamous cell carcinoma of the skin. Have demonstrated or suspected allergy to raloxifene or arzoxifene Have unexplained or abnormal vaginal bleeding within 6 months prior to Visit 1 or between Visit 1 and Visit 2. Are experiencing clinically severe postmenopausal symptoms that may require estrogen-replacement therapy. Have a history of or suggestion on ultrasound or pelvic examination of a pre-existing gynecologic abnormality that would require further gynecologic treatment (e.g., ovarian cysts, large fibroids, undiagnosed adnexal masses) or of baseline endometrial thickness of >5 mm. Have Papanicolaou's tests showing malignant or premalignant findings. Have active or any past history of thromboembolic events Have active or any past history of atrial fibrillation. Have a history of cerebrovascular accident or documented transient ischemic attack at any time in the past. Have acute or chronic liver disease defined as alanine aminotransaminase (ALT) >100 U/L, gamma-glutamyl transferase (GGT) >400 U/L, or late stage cirrhosis without transaminase elevations. Have impaired kidney function (serum creatinine >177 micromol/L or >2.0 mg/dL). Have vitamin D deficiency prior to enrollment (Visit 2; 25-hydroxyvitamin D less than10 ng/mL or less than 24.9 nmol/L). Have any known, severe, or untreated malabsorption syndromes. Have endocrine disorders requiring pharmacologic therapy except for type II diabetes and hypothyroidism. Patients on a stable dose of thyroid replacement therapy during the 6 months preceding randomization (Visit 2) who are clinically euthyroid in the opinion of the investigator may enroll in the trial. Consume an excess of alcohol or abuse drugs Represent an unacceptable medical or psychiatric risk for treatment with an investigational drug Have active or any history of seizure disorder.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: arzoxifene<br>* 20 mg, QD, PO,24 weeks<br>* Other names: LY353381;|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* QD, PO, 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lumbar spine bone mineral density (BMD), by dual energy X-ray absorptiometry (DXA) analyses |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of spontaneous vaginal bleeding. |  | 6 months | 
| Total hip BMD |  | 6 months | 
| Biochemical marker of bone metabolism (serum CTX and PINP) |  | 3 and to 6 months | 
| Overall safety of arzoxifene administration in Korean postmenopausal women |  | 6 months |