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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00439647
First received: February 22, 2007
Last updated: October 10, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Male Osteoporosis
Drug: Zoledronic acid 5 mg iv
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants With at Least One New Morphometric Vertebral Fracture Over 24 Months [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    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

  • Percentage of Participants With at Least One New Moderate or Severe Morphometric Vertebral Fracture Over 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    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 or Worsening Morphometric Vertebral Fracture Over 12 Months [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: from Baseline to 12 months and 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: Month 6, Month 12, Month 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Month 6, Month 12, Month 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Month 6, Month 12, Month 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Month 3, Month 6, Month 12, Month 15, month 18, Month 24 ] [ Designated as safety issue: No ]

Enrollment: 1199
Study Start Date: December 2006
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zoledronic Acid
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
Zoledronic acid 5 mg iv given once a year.
Other Names:
  • Aclasta,
  • Reclast
Placebo Comparator: Placebo
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
Placebo intravenous (i.v.) once a year

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00439647

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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Principal Investigator: Novartis Pharmaceuticals Novartis Argentina
Principal Investigator: Novartis Pharmaceuticals Novartis Belgium
Principal Investigator: Novartis Pharmaceuticals Novartis Brazil
Principal Investigator: Novartis Pharmaceuticals Novartis Czech Republic
Principal Investigator: Novartis Pharmaceuticals Novartis Denmark
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Principal Investigator: Novartis Pharmaceuticals Novartis Slovakia
Principal Investigator: Novartis Pharmaceuticals Novartis Sweden
Principal Investigator: Novartis Pharmaceuticals Novartis
Principal Investigator: Novartis Pharmaceuticals Novartis United Kingdom
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Principal Investigator: Novartis Pharmaceuticals Novartis Austria
Principal Investigator: Novartis Pharmaceuticals Novartis Iceland
Principal Investigator: Novartis Pharmaceuticals Novartis Poland
Principal Investigator: Novartis Pharmaceuticals Novartis Russia
Principal Investigator: Novartis Pharmaceuticals Novartis South Africa
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00439647     History of Changes
Other Study ID Numbers: CZOL446M2309
Study First Received: February 22, 2007
Results First Received: October 10, 2011
Last Updated: October 10, 2011
Health Authority: Argentina: National Administration of Drugs, Foods and Medical Technology
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: National Health Surveillance Agency
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Norway: Norwegian Medicines Agency
Portugal: National Pharmacy and Medicines Institute
Romania: Ministry of Health and the Family
Spain: Spanish Agency of Medicines
Slovakia: State Institute for Drug Control
Sweden: Medical Products Agency
Switzerland: Swiss Agency for Therapeudic Products
United Kingdom: Medicines and Healthcare Products Regulatory Agency
South Africa: Medicines Control Council (MCC)
Iceland:"Lyfjastofnun" Icelandic Medicines Control Agency
Poland: Central Register of Clinical Trials. The office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Italy: Ministero della Salute
Austria: Bundesamt für Sicherheit im Gesundheitswesen. AGES PharmMed, WIN/NATA
Australia:Therapeutic Goods Administration (TGA)
Russia:Federal Service on Surveillance in Healthcare and Social Development of Russian Federation

Keywords provided by Novartis:
Osteoporosis
males
vertebral fractures
clinical fractures
bone mineral density
bone biomarkers
zoledronic acid

Additional relevant MeSH terms:
Fractures, Bone
Osteoporosis
Wounds and Injuries
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014