Effects of Zoledronic Acid and Raloxifene on Bone Turnover Markers in Postmenopausal Women With Low Bone Mineral Density

Study Overview
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Brief Summary
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This study will compare the effects of Zoledronic acid and Raloxifene in reducing bone turnover markers in postmenopausal women with low bone mineral density over 6 months.

Official Title
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A Multi-center, Randomized, Double-blind, Double-dummy Study in Postmenopausal Women With Low Bone Mineral Density to Compare the Effects of a Single Dose of i.v. Zoledronic Acid 5 mg, With Daily Oral Raloxifene 60 mg OD on Bone Turnover Markers

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: Raloxifene
* Drug: Zoledronic acid
* Drug: Placebo oral pills
* Drug: Placebo intravenous (i.v.) infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females, between 45 and 80 years (inclusive) of age, considered post-menopausal according to one of the following guidelines: Cessation of menses for 18 months in women < 50 years of age Cessation of menses for 12 months in women age 50 years or over Documented bilateral oophorectomy at least 1 year previously Documented T score of less than or equal to -1.5 on dual energy X-ray absorptiometry (DXA) scan at the lumbar spine, total hip or femoral neck within 24 months prior to screening, and clinically indicated for treatment with bisphosphonates (BPs) for osteopenia or osteoporosis Signed informed consent prior to initiation of any study procedure Exclusion Criteria: Prior treatment with i.v. bisphosphonates within the last 2 years Previous use of oral bisphosphonates within the past 2 years (unless used for less than 8 weeks*). *NOTE: If used less than 8 weeks, the washout period is 6 months. Treatment with raloxifene, calcitonin, tibolone or hormone replacement therapy. The washout period for these medications is 6 months prior to randomization. Any treatment with strontium renalate, sodium fluoride or parathyroid hormone Use of systemic high dose corticosteroids at an average dose of ≥ 7.5 mg per day of oral prednisone or equivalent for a period of three months or more within the previous year Treatment with any investigational drug within 30 days prior to randomization Any woman of child bearing potential Patients with fractures occurring within three months prior to randomization History of hypersensitivity to bisphosphonates History of non-traumatic uveitis or iritis, within 2 years prior to study entry. A history of invasive malignancy of any organ system, treated or untreated, within the past 12 months prior to screening; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, Ductal Carcinoma in-situ (DCIS) that has been surgically removed, and Carcinoma in-situ (CIS) of the uterine cervix that has been surgically removed. Previous major solid organ transplant recipient or on a transplant waiting list History of hyperparathyroidism, hypoparathyroidism, Osteogenesis imperfecta, Paget's disease or any metabolic bone disease other than osteoporosis Any medical condition which would interfere with the action of the study drug or limit life expectancy to less than 6 months Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial Active dental infection, unhealed dental extraction or planned oral surgery within 3 month prior to randomization. Calculated creatinine clearance < 30 mL/min Greater than 2+ protein on urine dipstick without evidence of contamination or bacteriuria (may be repeated one time, at least a day apart). Serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.08 mmol/L (8.3 mg/dL) at screening AST, ALT or serum alkaline phosphatase greater than twice the upper limit of normal

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: Zoledronic Acid<br>Zoledronic acid 5 mg (single i.v. infusion) + daily oral placebo for 6 months (zoledronic acid group) | Drug: Zoledronic acid<br> <br> * Other names: Reclast, Aclasta;Drug: Placebo oral pills<br> <br> |
| Active Comparator: Raloxifene<br>Placebo (single i.v. infusion) + oral raloxifene 60 mg/day for 6 months (raloxifene group) | Drug: Raloxifene<br> <br> Drug: Placebo intravenous (i.v.) infusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Urine N-telopeptide of Type 1 Collagen (NTx.) | The primary efficacy variable was the change from baseline in urine NTx (corrected by creatinine). The primary analysis time point was at 6 months of treatment. The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine. | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Urine NTx at 2 Months | The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine. | Baseline and 2 months | 
| Change From Baseline in Urine NTx at 4 Months | The results are reported as nanomoles (nM) of bone collagen equivalents (BCE) per millimole (mM) of urine creatinine. | Baseline and 4 months | 
| Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 2 Months |  | Baseline and 2 months | 
| Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 4 Months |  | Baseline and 4 months | 
| Change From Baseline in Serum Bone Specific Alkaline Phosphatase (BSAP) at 6 Months |  | Baseline and 6 months | 
| Overall Principal Investigator Satisfaction Assessed by Satisfaction Questionnaire | The investigator was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: not at all, a little, somewhat, quite, or completely. | Immediately after infusion procedure | 
| Overall Nurse Satisfaction Assessed by Satisfaction Questionnaire | The study coordinator (nurse) was asked to complete satisfaction questionnaires at baseline (Visit 2/Day 1) when each patient's i.v. drug administration occurred. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: not at all, a little, somewhat, quite, or completely. | Immediately after infusion procedure | 
| Overall Patient Satisfaction Assessed by Satisfaction Questionnaire | Patients were asked to complete the satisfaction questionnaire at baseline. The questionnaire assessed overall satisfaction with the i.v. infusion procedure. The possible answers to the question were: not at all, a little, somewhat, quite, or completely. | Immediately after infusion procedure | 
| Patient Preference at 6 Months for Annual i.v Therapy or Daily Oral Regimens | At the end-of-study visit, Month 6, patients were asked to complete a questionnaire to assess preference for the different treatment modalities (annual i.v. infusion vs. daily oral capsule). The possible answers to question were: once a year i.v. infusion, once daily pill, or both are equal. | At 6 month visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Post-menopausal, Bone mineral density