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

Primary Purpose

Male Osteoporosis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Zoledronic acid 5 mg iv

Placebo

About this trial

This is an interventional treatment trial for Male Osteoporosis focused on measuring Osteoporosis, males, vertebral fractures, clinical fractures, bone mineral density, bone biomarkers, zoledronic acid

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Zoledronic Acid

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 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.

Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 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)

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)

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

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.

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.

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.

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)

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)

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)

Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits

Full Information

NCT ID

NCT00439647

First Posted

February 22, 2007

Last Updated

April 19, 2017

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00439647

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2011

Overall Recruitment Status

Completed

Study Start Date

December 2006 (undefined)

Primary Completion Date

October 2010 (Actual)

Study Completion Date

October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Male Osteoporosis

Keywords

Osteoporosis, males, vertebral fractures, clinical fractures, bone mineral density, bone biomarkers, zoledronic acid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

1199 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Zoledronic Acid

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Zoledronic acid 5 mg iv

Other Intervention Name(s)

Aclasta,, Reclast

Intervention Description

Zoledronic acid 5 mg iv given once a year.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo intravenous (i.v.) once a year

Primary Outcome Measure Information:

Title

Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 24 Months

Description

Time Frame

24 Months

Secondary Outcome Measure Information:

Title

Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 12 Months

Description

Time Frame

12 Months

Title

Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 12 Months

Description

Time Frame

12 months

Title

Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 24 Months

Description

Time Frame

24 Months

Title

Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 12 Months

Description

Time Frame

Baseline, 12 months

Title

Percentage of Participants With at Least One New or Worsening Morphometric Vertebral Fracture Over 24 Months

Description

Time Frame

Baseline, Month 24

Title

Mean Change in Height From Baseline

Description

Time Frame

from Baseline to 12 months and 24 months

Title

Number of Participants With First Clinical Vertebral Fracture

Description

Time Frame

24 months

Title

Number of Participants With First Clinical Fracture

Description

Time Frame

24 months

Title

Number of Participants With First Non-vertebral Fracture

Description

Time Frame

24 months

Title

Percentage Change From Baseline in Lumbar Spine Bone Mass Density (BMD)

Description

Time Frame

Month 6, Month 12, Month 24

Title

Percentage Change From Baseline in Total Hip BMD (g/CM^2)

Description

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)

Time Frame

Month 6, Month 12, Month 24

Title

Percentage Change From Baseline in Femoral Neck BMD (g/CM^2)

Description

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)

Time Frame

Month 6, Month 12, Month 24

Title

Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits

Time Frame

Baseline, Month 3, Month 6, Month 12, Month 15, month 18, Month 24

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials: