A Study to Evaluate Alendronate Sodium /Vitamin D3 Combination Tablets(FOSAMAX PLUS) Versus Calcitriol in the Treatment of Osteoporosis in Postmenopausal Women in China (MK-0217A-264)

Study Overview
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Brief Summary
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This study will evaluate whether the once weekly administration of the combination tablet alendronate/vitamin D3 (FOSAMAX PLUS) will increase lumbar spine bone mineral density (BMD) more than the daily use of calcitriol.

Detailed Description
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This was a 6-month, randomized, open-label, active-comparator controlled, parallel-group study with a 6-month extension to evaluate the safety and efficacy of alendronate sodium 70 mg plus vitamin D3 5600 IU combination tablets versus calcitriol in the treatment of osteoporosis in postmenopausal women in China. Participants were randomly assigned to receive alendronate 70 mg plus vitamin D3 5600 IU combination tablet once weekly orally or calcitriol 0.25 μg daily orally.

Official Title
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A 6-Month, Randomized, Open-Label, Active-Comparator Controlled, Parallel-Group Study With a 6-Month Extension to Evaluate the Safety and Efficacy of Alendronate Sodium 70 mg/Vitamin D3 5600 I.U. Combination Tablets Versus Calcitriol in the Treatment of Osteoporosis in Postmenopausal Women in China

Conditions
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Osteoporosis, Postmenopausal

Intervention / Treatment
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* Drug: alendronate 70-mg/vitamin D3 5600 IU combination tablet (Fosamax Plus)
* Drug: Calcitriol
* Dietary Supplement: Calcium 500 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets one of the following BMD criteria: Has BMD T-score ≤-2.5 in at least one of the anatomic sites including lumbar spine, total hip, and femoral neck, OR Has prior non-pathological fragility fracture (of spine, wrist, humerus or clavicle) and BMD T-score ≤-1.5 in at least one of the anatomic sites including lumbar spine, total hip, and femoral neck sites Must have a baseline 25-hydroxyvitamin D ≥8 ng/mL (20 nmol/L) Is ambulatory Has been postmenopausal for at least one year Exclusion Criteria: Has any contraindication to alendronate, including abnormalities of the esophagus which delay esophageal emptying (such as stricture or achalasia), or inability to stand/sit upright for at least 30 minutes, or hypersensitivity to alendronate and vitamin D, or hypocalcemia Has any contraindications to calcitriol, and/or vitamin D, including hypercalcemia, hypercalciuria, or active kidney stone disease Had a prior hip fracture Has received treatment with any of the following: anabolic steroid agent within the past 12 months, systemic glucocorticoids for more than 2 weeks in the past 6 months, oral bisphosphonates more than 3 months within the past 2 years, any lifetime use of an intravenous administration of zoledronate, immunosuppressant other than methotrexate, fluoride treatment at a dose greater than 1 mg/day for more than 2 weeks within the past 3 months, strontium containing products for more than 2 weeks within the past 6 months, Parathyroid hormone for more than 2 weeks within the past 3 months, current use of chemotherapy, or heparin, growth hormone for more than 2 weeks within the past 6 months, active hormonal vitamin D analogs (e.g., alphacalcidol, calcitriol) in the past 30 days, or more than 5 days treatment of active hormonal vitamin D analogs between 30 and 60 days prior to study entry., use of vitamin A (excluding beta carotene) >10,000 IU daily, unless willing to discontinue this dose during the study, current use of, lithium, or anti-convulsants, current use of calcium supplement in amount excess of 1500 mg daily, unless willing to discontinue this dose during the study, estrogen with or without progestin within the prior 6 months, Raloxifene or other selective estrogen receptor modulator ([SERM] including tamoxifen), tibolone, or an aromatase inhibitor within the prior 6 months and/or sub-cutaneous calcitonin or intra-nasal calcitonin within the prior 6 months Has a history of malignancy within previous 5 years Has one or more of the following concomitant conditions: uncontrolled upper gastrointestinal disorders, myocardial infarction, unstable angina, stroke and revascularization condition within 3 months, malabsorption syndrome, uncontrolled primary or secondary hyperparathyroidism, uncontrolled thyroid disease, renal insufficiency, uncontrolled genitourinary, cardiovascular, hepatic, renal, endocrine, hematologic, neurological, psychiatric, or pulmonary diseases; unexplained laboratory test abnormality or other conditions, uncontrolled hypertension, new onset diabetes (within 3 months), poorly controlled hyperglycemia or abnormal fasting glucose, hypoglycemia for any cause, history of, or evidence for metabolic bone disease other than osteoporosis, abnormal serum calcium or phosphate, and/or active renal stone disease when a calcium supplement is contraindicated

Ages Eligible for Study
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Minimum Age: 56 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fosamax Plus<br>Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study). | Drug: alendronate 70-mg/vitamin D3 5600 IU combination tablet (Fosamax Plus)<br>* one combination tablet once weekly<br>* Other names: MK-0217A;Dietary Supplement: Calcium 500 mg<br>* one 500 mg tablet once daily<br>|
| Active Comparator: Calcitriol<br>Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study). | Drug: Calcitriol<br>* 0.25 μg once daily orally<br>Dietary Supplement: Calcium 500 mg<br>* one 500 mg tablet once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Base Study: Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 6 | BMD at the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA) at baseline and Month 6. | Baseline and Month 6 | 
| Extension Study: Percentage Change From Baseline in Lumbar Spine BMD at Month 12 | BMD at the lumbar spine was assessed by DXA at baseline and Month 12. | Baseline and Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Base Study: Percentage Change From Baseline in Serum Procollagen Type 1 N-Terminal Propeptide (s-P1NP) at Month 6 | s-P1NP is a biochemical marker of bone turnover that is particularly useful in monitoring bone resorption, a process by which bone is broken down within the body. s-P1NP was measured at baseline and Month 6. | Baseline and Month 6 | 
| Base Study: Percentage Change From Baseline in Serum C-Telopeptides of Type 1 Collagen (s-CTx) at Month 6 | s-CTx is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. s-CTx was measured at baseline and Month 6. | Baseline and Month 6 | 
| Extension Study: Percentage Change From Baseline in s-P1NP at Month 12 | s-P1NP is a biochemical marker of bone turnover that is particularly useful in monitoring bone resorption, a process by which bone is broken down within the body. s-P1NP was measured at baseline and Month 12. | Baseline and Month 12 | 
| Extension Study: Percentage Change From Baseline in s-CTx at Month 12 | s-CTx is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. s-CTx was measured at baseline and Month 12. | Baseline and Month 12 |