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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00439647




Registration number
NCT00439647
Ethics application status
Date submitted
22/02/2007
Date registered
23/02/2007
Date last updated
21/04/2017

Titles & IDs
Public title
Efficacy in Reducing Fractures and Safety of Zoledronic Acid in Men With Osteoporosis
Scientific 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
Secondary ID [1] 0 0
CZOL446M2309
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Male Osteoporosis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Zoledronic acid 5 mg iv
Treatment: Drugs - Placebo

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.

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.


Treatment: Drugs: Zoledronic acid 5 mg iv
Zoledronic acid 5 mg iv given once a year.

Treatment: Drugs: Placebo
Placebo intravenous (i.v.) once a year

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
24 Months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
12 Months
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
24 Months
Secondary outcome [4] 0 0
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)
Timepoint [4] 0 0
Baseline, 12 months
Secondary outcome [5] 0 0
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)
Timepoint [5] 0 0
Baseline, Month 24
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
from Baseline to 12 months and 24 months
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
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)
Timepoint [10] 0 0
Month 6, Month 12, Month 24
Secondary outcome [11] 0 0
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)
Timepoint [11] 0 0
Month 6, Month 12, Month 24
Secondary outcome [12] 0 0
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)
Timepoint [12] 0 0
Month 6, Month 12, Month 24
Secondary outcome [13] 0 0
Serum Beta C-terminal Telopeptides of Type I Collagen(b-CTx) by Visits
Timepoint [13] 0 0
Baseline, Month 3, Month 6, Month 12, Month 15, month 18, Month 24

Eligibility
Key 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
Minimum age
50 Years
Maximum age
85 Years
Gender
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Novartis Investigative Site - Geelong-VIC
Recruitment hospital [2] 0 0
Novartis Investigative Site - Maroochydore-QLD
Recruitment hospital [3] 0 0
Novartis Investigative Site - Randwick-NSW
Recruitment postcode(s) [1] 0 0
- Geelong-VIC
Recruitment postcode(s) [2] 0 0
- Maroochydore-QLD
Recruitment postcode(s) [3] 0 0
- Randwick-NSW
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Cordoba
Country [3] 0 0
Argentina
State/province [3] 0 0
Mar del Plata
Country [4] 0 0
Argentina
State/province [4] 0 0
San Miguel de Tucuman
Country [5] 0 0
Austria
State/province [5] 0 0
Graz
Country [6] 0 0
Austria
State/province [6] 0 0
Vienna
Country [7] 0 0
Belgium
State/province [7] 0 0
Bruxelles
Country [8] 0 0
Belgium
State/province [8] 0 0
Diepenbeek
Country [9] 0 0
Belgium
State/province [9] 0 0
Genk
Country [10] 0 0
Belgium
State/province [10] 0 0
Godinne
Country [11] 0 0
Belgium
State/province [11] 0 0
Gozee
Country [12] 0 0
Belgium
State/province [12] 0 0
Jette
Country [13] 0 0
Belgium
State/province [13] 0 0
Laeken
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Belgium
State/province [15] 0 0
Liege
Country [16] 0 0
Belgium
State/province [16] 0 0
Merksem
Country [17] 0 0
Belgium
State/province [17] 0 0
Wilrijk
Country [18] 0 0
Brazil
State/province [18] 0 0
Brasilia
Country [19] 0 0
Brazil
State/province [19] 0 0
Curitiba
Country [20] 0 0
Brazil
State/province [20] 0 0
Rio de Janeiro
Country [21] 0 0
Brazil
State/province [21] 0 0
Sao Paulo
Country [22] 0 0
Czechia
State/province [22] 0 0
Ceske Budejovice
Country [23] 0 0
Czechia
State/province [23] 0 0
Hradec Kralove
Country [24] 0 0
Czechia
State/province [24] 0 0
Plzen
Country [25] 0 0
Czechia
State/province [25] 0 0
Prague
Country [26] 0 0
Czechia
State/province [26] 0 0
Praha
Country [27] 0 0
Denmark
State/province [27] 0 0
Aalborg
Country [28] 0 0
Denmark
State/province [28] 0 0
Arhus
Country [29] 0 0
Denmark
State/province [29] 0 0
Glostrup
Country [30] 0 0
Denmark
State/province [30] 0 0
Hvidovre
Country [31] 0 0
Denmark
State/province [31] 0 0
Odense C
Country [32] 0 0
Finland
State/province [32] 0 0
Helsinki
Country [33] 0 0
Finland
State/province [33] 0 0
Tampere
Country [34] 0 0
Finland
State/province [34] 0 0
Turku
Country [35] 0 0
Germany
State/province [35] 0 0
Aachen
Country [36] 0 0
Germany
State/province [36] 0 0
Bad Bentheim
Country [37] 0 0
Germany
State/province [37] 0 0
Bad Pyrmont
Country [38] 0 0
Germany
State/province [38] 0 0
Braunfels
Country [39] 0 0
Germany
State/province [39] 0 0
Dresden
Country [40] 0 0
Germany
State/province [40] 0 0
Essen
Country [41] 0 0
Germany
State/province [41] 0 0
Frankfurt
Country [42] 0 0
Germany
State/province [42] 0 0
Hamburg
Country [43] 0 0
Germany
State/province [43] 0 0
Hannover
Country [44] 0 0
Germany
State/province [44] 0 0
Heidelberg
Country [45] 0 0
Germany
State/province [45] 0 0
Kempen
Country [46] 0 0
Germany
State/province [46] 0 0
Leverkusen
Country [47] 0 0
Germany
State/province [47] 0 0
Magdeburg
Country [48] 0 0
Germany
State/province [48] 0 0
Marburg
Country [49] 0 0
Germany
State/province [49] 0 0
München
Country [50] 0 0
Germany
State/province [50] 0 0
Würzburg
Country [51] 0 0
Hungary
State/province [51] 0 0
Budapest
Country [52] 0 0
Hungary
State/province [52] 0 0
Debrecen
Country [53] 0 0
Hungary
State/province [53] 0 0
Gyula
Country [54] 0 0
Hungary
State/province [54] 0 0
Szekesfehervar
Country [55] 0 0
Hungary
State/province [55] 0 0
Veszprem
Country [56] 0 0
Iceland
State/province [56] 0 0
Kopavogur
Country [57] 0 0
Italy
State/province [57] 0 0
Arenzano
Country [58] 0 0
Italy
State/province [58] 0 0
Siena-SI
Country [59] 0 0
Italy
State/province [59] 0 0
Valeggio Sul Mincio
Country [60] 0 0
Norway
State/province [60] 0 0
Elverum
Country [61] 0 0
Norway
State/province [61] 0 0
Gjettum
Country [62] 0 0
Norway
State/province [62] 0 0
Hamar
Country [63] 0 0
Norway
State/province [63] 0 0
Oslo
Country [64] 0 0
Norway
State/province [64] 0 0
Paradis
Country [65] 0 0
Norway
State/province [65] 0 0
Trondheim
Country [66] 0 0
Poland
State/province [66] 0 0
Bialystok
Country [67] 0 0
Poland
State/province [67] 0 0
Warszawa
Country [68] 0 0
Portugal
State/province [68] 0 0
Lisbon
Country [69] 0 0
Portugal
State/province [69] 0 0
Ponte de Lima
Country [70] 0 0
Romania
State/province [70] 0 0
Bucharest
Country [71] 0 0
Romania
State/province [71] 0 0
Cluj Napoca
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Moscow
Country [73] 0 0
Russian Federation
State/province [73] 0 0
St. Petersburg
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Tyumen
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Yaroslavl
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Yekaterinburg
Country [77] 0 0
Slovakia
State/province [77] 0 0
Banska Bystrica
Country [78] 0 0
Slovakia
State/province [78] 0 0
Bratislava
Country [79] 0 0
Slovakia
State/province [79] 0 0
Kosice
Country [80] 0 0
Slovakia
State/province [80] 0 0
Lubochna
Country [81] 0 0
Slovakia
State/province [81] 0 0
Piestany
Country [82] 0 0
South Africa
State/province [82] 0 0
Cape Town
Country [83] 0 0
South Africa
State/province [83] 0 0
Rosebank-Johannesburg
Country [84] 0 0
South Africa
State/province [84] 0 0
Western Cape
Country [85] 0 0
Spain
State/province [85] 0 0
Alicante
Country [86] 0 0
Spain
State/province [86] 0 0
Barcelona
Country [87] 0 0
Spain
State/province [87] 0 0
Cordoba
Country [88] 0 0
Spain
State/province [88] 0 0
Granada
Country [89] 0 0
Spain
State/province [89] 0 0
Hospitalet de Llobregat
Country [90] 0 0
Spain
State/province [90] 0 0
Madrid
Country [91] 0 0
Spain
State/province [91] 0 0
Malaga
Country [92] 0 0
Spain
State/province [92] 0 0
Merida
Country [93] 0 0
Spain
State/province [93] 0 0
Oviedo
Country [94] 0 0
Spain
State/province [94] 0 0
Sabadell
Country [95] 0 0
Spain
State/province [95] 0 0
Salamanca
Country [96] 0 0
Spain
State/province [96] 0 0
Santander
Country [97] 0 0
Spain
State/province [97] 0 0
Sevilla
Country [98] 0 0
Spain
State/province [98] 0 0
Valencia
Country [99] 0 0
Spain
State/province [99] 0 0
Villajoyosa
Country [100] 0 0
Sweden
State/province [100] 0 0
Gothenburg
Country [101] 0 0
Sweden
State/province [101] 0 0
Linkoeping
Country [102] 0 0
Sweden
State/province [102] 0 0
Lund
Country [103] 0 0
Sweden
State/province [103] 0 0
Malmo
Country [104] 0 0
Sweden
State/province [104] 0 0
Orebro
Country [105] 0 0
Sweden
State/province [105] 0 0
Stockholm
Country [106] 0 0
Sweden
State/province [106] 0 0
Umea
Country [107] 0 0
Sweden
State/province [107] 0 0
Uppsala
Country [108] 0 0
Switzerland
State/province [108] 0 0
Aarau
Country [109] 0 0
Switzerland
State/province [109] 0 0
Baden
Country [110] 0 0
Switzerland
State/province [110] 0 0
Basel
Country [111] 0 0
Switzerland
State/province [111] 0 0
Bern
Country [112] 0 0
Switzerland
State/province [112] 0 0
Geneve
Country [113] 0 0
Switzerland
State/province [113] 0 0
Lausanne
Country [114] 0 0
Switzerland
State/province [114] 0 0
Sion
Country [115] 0 0
Switzerland
State/province [115] 0 0
Zuerich
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Aberdeen
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Chorley
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Glasgow
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Kent
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Liverpool
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Manchester
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Middx
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Newcastle Upon Tyne
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Nottingham
Country [125] 0 0
United Kingdom
State/province [125] 0 0
Penarth
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Reading-Berkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00439647
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Argentina
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications