Efficacy in Reducing Fractures and Safety of Zoledronic Acid in Men With Osteoporosis

Study Overview
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Brief Summary
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This study will investigate if the drug zoledronic acid given once yearly is safe and has beneficial effects in treating osteoporosis by reducing bone loss and fractures in men with osteoporosis.

Official Title
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A Two Year Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Fracture Efficacy and Safety of Intravenous Zoledronic Acid 5 mg Annually for the Treatment of Osteoporosis in Men

Conditions
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Male Osteoporosis

Intervention / Treatment
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* Drug: Zoledronic acid 5 mg iv
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Osteoporosis as defined by very low bone mineral density in the hip and spine or low bone mineral density in the hip combined with presence of 1-3 mild or moderate fractures of the vertebrae Exclusion Criteria: Low Vitamin D Renal insufficiency Previous treatment with certain anti-osteoporotic therapies (except after certain washout periods): calcitonin, bisphosphonates, parathyroid hormone (PTH), sodium fluoride, strontium ranelate, Previous treatment with testosterone, anabolic steroids or growth hormone Chronic use of systemic corticosteroids (oral or i.v.) within the last year History of any cancer or metastases within the last 5 years History of brittle bone disease, multiple myeloma, or Paget's disease, or any other metabolic bone disease, except osteoporosis Bilateral hip replacements Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Male

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: Zoledronic Acid<br>5 mg/100 ml administered via a peripheral intravenous site as a slow infusion over 15 minutes. The intravenous (i.v.) infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year. | Drug: Zoledronic acid 5 mg iv<br>* Zoledronic acid 5 mg iv given once a year.<br>* Other names: Reclast;|
| Placebo Comparator: Placebo<br>100 ml Placebo administered via a peripheral intravenous site as a slow infusion over 15 minutes. The i.v. infusion was delivered via vented infusion line (to allow constant flow) and 20-22 gauge angiocatheter, and preceded and followed by a 10 ml normal saline flush of the intravenous line for a total volume infused of 120 ml once a year. | Drug: Placebo<br>* Placebo intravenous (i.v.) once a year<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 24 Months | Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 12 Months | Vertebral fracture (VF) was assessed based on morphometry. QM(quantitative morphometry) incident VF(QM positive) is defined by at least 20% decrease in vertebral height of at least 4mm. If participant had QM positive at any vertebrae at any visit, x-rays from visits for participants were evaluated using Genant semi-quantitative method for VF assessment: Grade1 Mild VF is defined as 20-24% decrease in anterior, middle, and/or posterior vertebral height. Grade2 moderate VF is defined as 25-40% decrease in vertebral height. Grade3 Severe VF is defined as more than 40% decrease in vertebral height | 12 Months | 
| Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 12 Months | Moderate or severe vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. Grade 2 moderate VF was defined as a 25-40% reduction in any vertebral height.Grade 3 Severe: VF was defined as more than 40% reduction in any vertebral height. | 12 months | 
| Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 24 Months | Moderate or severe vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. Grade 2 moderate VF was defined as a 25-40% reduction in any vertebral height.Grade 3 Severe: VF was defined as more than 40% reduction in any vertebral height. | 24 Months | 
| Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 12 Months | Worsening vertebral fracture (VF) was assessed based on morphometry. QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit, x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture) | Baseline, 12 months | 
| Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 24 Months | Worsening vertebral fracture (VF) was assessed based on morphometry. A QM (quantitative morphometry) incident VF(QM positive) was defined by at least a 20% decrease in any vertebral height (at least 4 mm). If a participant had a QM positive at any vertebrae at any visit,x-rays from all visits for participants were evaluated using Genant semi-quantitative (SQ) method for VF assessment. A worsening fracture was defined as an SQ reading that was greater than the baseline SQ reading, which was at least 1 (prevalent fracture) | Baseline, Month 24 | 
| Mean Change in Height From Baseline | Height was measured using a stadiometer. Two measurements were taken in millimeters (mm), and repeated if the two measurements differed by greater than 4 mm. The average of the two (or four) height measurements was used for analysis | from Baseline to 12 months and 24 months | 
| Number of Participants With First Clinical Vertebral Fracture | Clinical vertebral fracture is a painful vertebral fracture which came to clinical attention, e.g., with increased back pain, impairment of mobility or functional limitations. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier. | 24 months | 
| Number of Participants With First Clinical Fracture | Clinical fracture is painful fracture in any site which came to clinical attention, e.g., with increased pain, impaired mobility or functional limitations. Subjects who did not experience fracture were censored at end of study. End of study was defined as the earlier of last visit or date of death. | 24 months | 
| Number of Participants With First Non-vertebral Fracture | Non-vertebral fracture is any fracture which was not of the vertebrae. Subjects who did not experience a fracture event were censored at the end of study. End of study was defined as the last visit or date of death, whichever was earlier. | 24 months | 
| Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD) | Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in BMD at lumbar spine at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100*(endpoint - baseline) | Month 6, Month 12, Month 24 | 
| Percentage Change From Baseline in Total Hip BMD (g/CM^2) | Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total hip BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100*(endpoint - baseline) | Month 6, Month 12, Month 24 | 
| Percentage Change From Baseline in Femoral Neck BMD (g/CM^2) | Dual energy x-ray absorptiometry (DXA) Least Square Means (LSM) were analyzed using an ANCOVA model with treatment and baseline value as explanatory variables. Percent change in total femoral neck BMD at Months 6, 12, and 24 relative to baseline as measured by DXA in a subset of at least 100 evaluable subjects at selected sites. Percentage change from baseline = 100*(endpoint - baseline) | Month 6, Month 12, Month 24 | 
| Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits |  | Baseline, Month 3, Month 6, Month 12, Month 15, month 18, Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, males, vertebral fractures, clinical fractures, bone mineral density, bone biomarkers, zoledronic acid