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

February 22, 2007
October 10, 2011
December 2006
October 2010   (final data collection date for primary outcome measure)
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
Proportion of patients with at least one new vertebral fracture over 24 months
Complete list of historical versions of study NCT00439647 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Time to first clinical fracture (vertebral/ non-vertebral)
  • Change in height at Month 12 and Month 24
  • Percent change of bone mineral density (BMD) at lumbar spine and total hip at Month 6, Month 12 and Month 24 relative to baseline in a sub-set of at least 100 evaluable patients
  • Changes in biochemical markers of bone resorption and bone formation at month 3, 6, 12, 15, 18 and 24 relative to baseline in a sub-set of at least 100 evaluable patients
  • Overall safety of zoledronic acid compared to placebo in osteoporotic men
Not Provided
Not Provided
 
Efficacy in Reducing Fractures and Safety of Zoledronic Acid in Men With Osteoporosis
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Male Osteoporosis
  • Drug: Zoledronic acid 5 mg iv
    Zoledronic acid 5 mg iv given once a year.
    Other Names:
    • Aclasta,
    • Reclast
  • Drug: Placebo
    Placebo intravenous (i.v.) once a year
  • 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.
    Intervention: Drug: Zoledronic acid 5 mg iv
  • 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.
    Intervention: Drug: Placebo
Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J, Langdahl B, Rizzoli R, Lipschitz S, Dimai HP, Witvrouw R, Eriksen E, Brixen K, Russo L, Claessens F, Papanastasiou P, Antunez O, Su G, Bucci-Rechtweg C, Hruska J, Incera E, Vanderschueren D, Orwoll E. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012 Nov;367(18):1714-23. doi: 10.1056/NEJMoa1204061.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1199
October 2010
October 2010   (final data collection date for primary outcome measure)

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

Male
50 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Austria,   Belgium,   Brazil,   Czech Republic,   Denmark,   Finland,   Germany,   Hungary,   Iceland,   Italy,   Norway,   Poland,   Portugal,   Romania,   Russian Federation,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   United Kingdom
 
NCT00439647
CZOL446M2309
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
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
Principal Investigator: Novartis Pharmaceuticals Novartis Finland
Principal Investigator: Novartis Pharmaceuticals Novartis Germany
Principal Investigator: Novartis Pharmaceuticals Novartis Hungary
Principal Investigator: Novartis Pharmaceuticals Novartis Norway
Principal Investigator: Novartis Pharmaceuticals Novartis Portugal
Principal Investigator: Novartis Pharmaceuticals Novartis Romania
Principal Investigator: Novartis Pharmaceuticals Novartis Spain
Principal Investigator: Novartis Pharmaceuticals Novartis Slovakia
Principal Investigator: Novartis Pharmaceuticals Novartis Sweden
Principal Investigator: Novartis Pharmaceuticals Novartis
Principal Investigator: Novartis Pharmaceuticals Novartis United Kingdom
Principal Investigator: Novartis Pharmaceuticals Novartis Australia
Principal Investigator: Novartis Pharmaceuticals Novartis Italy
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
Novartis
October 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP