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

Male Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00439647
• Other study ID #: CZOL446M2309
• Status: Completed
• Phase: Phase 3
• First received: February 22, 2007
• Last updated: April 19, 2017
• Start date: December 2006
• Est. completion date: October 2010

Study information

• Verified date: October 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1199
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Male Osteoporosis
• Osteoporosis

Intervention

Drug:
• Zoledronic acid 5 mg iv
Zoledronic acid 5 mg iv given once a year.
• Placebo
Placebo intravenous (i.v.) once a year

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Mar del Plata
Argentina	Novartis Investigative Site	San Miguel de Tucuman
Australia	Novartis Investigative Site	Geelong-VIC
Australia	Novartis Investigative Site	Maroochydore-QLD
Australia	Novartis Investigative Site	Randwick-NSW
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Diepenbeek
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Godinne
Belgium	Novartis Investigative Site	Gozee
Belgium	Novartis Investigative Site	Jette
Belgium	Novartis Investigative Site	Laeken
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Merksem
Belgium	Novartis Investigative Site	Wilrijk
Brazil	Novartis Investigative Site	Brasilia
Brazil	Novartis Investigative Site	Curitiba
Brazil	Novartis Investigative Site	Rio de Janeiro
Brazil	Novartis Investigative Site	Sao Paulo
Czechia	Novartis Investigative Site	Ceske Budejovice
Czechia	Novartis Investigative Site	Hradec Kralove
Czechia	Novartis Investigative Site	Plzen
Czechia	Novartis Investigative Site	Prague
Czechia	Novartis Investigative Site	Praha
Denmark	Novartis Investigative Site	Aalborg
Denmark	Novartis Investigative Site	Arhus
Denmark	Novartis Investigative Site	Glostrup
Denmark	Novartis Investigative Site	Hvidovre
Denmark	Novartis Investigative Site	Odense C
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Tampere
Finland	Novartis Investigative Site	Turku
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Bad Bentheim
Germany	Novartis Investigative Site	Bad Pyrmont
Germany	Novartis Investigative Site	Braunfels
Germany	Novartis Investigative site	Dresden
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Kempen
Germany	Novartis Investigative Site	Leverkusen
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Würzburg
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Gyula
Hungary	Novartis Investigative Site	Szekesfehervar
Hungary	Novartis Investigative Site	Veszprem
Iceland	Novartis Investigative site	Kopavogur
Italy	Novartis Investigative site	Arenzano
Italy	Novartis Investigative site	Siena-SI
Italy	Novartis Investigative site	Valeggio Sul Mincio
Norway	Novartis Investigative Site	Elverum
Norway	Novartis Investigative Site	Gjettum
Norway	Novartis Investigative Site	Hamar
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Paradis
Norway	Novartis Investigative Site	Trondheim
Poland	Novartis Investigative site	Bialystok
Poland	Novartis Investigative site	Warszawa
Portugal	Novartis Investigative Site	Lisbon
Portugal	Novartis Investigative Site	Ponte de Lima
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Cluj Napoca
Russian Federation	Novartis Investigative site	Moscow
Russian Federation	Novartis Investigative site	St. Petersburg
Russian Federation	Novartis Investigative site	Tyumen
Russian Federation	Novartis Investigative site	Yaroslavl
Russian Federation	Novartis Investigative site	Yekaterinburg
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative site	Lubochna
Slovakia	Novartis Investigative Site	Piestany
South Africa	Novartis Investigative site	Cape Town
South Africa	Novartis Investigative site	Rosebank-Johannesburg
South Africa	Novartis Investigative site	Western Cape
Spain	Novartis Investigative Site	Alicante
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Cordoba
Spain	Novartis Investigative Site	Granada
Spain	Novartis Investigative Site	Hospitalet de Llobregat
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga
Spain	Novartis Investigative Site	Merida
Spain	Novartis Investigative Site	Oviedo
Spain	Novartis Investigative Site	Sabadell
Spain	Novartis Investigative Site	Salamanca
Spain	Novartis Investigative Site	Santander
Spain	Novartis Investigative Site	Sevilla
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Villajoyosa
Sweden	Novartis investigative site	Gothenburg
Sweden	Novartis investigative site	Linkoeping
Sweden	Novartis investigative site	Lund
Sweden	Novartis investigative site	Malmo
Sweden	Novartis investigative site	Orebro
Sweden	Novartis investigative site	Stockholm
Sweden	Novartis investigative site	Umea
Sweden	Novartis investigative site	Uppsala
Switzerland	Novartis Investigative Site	Aarau
Switzerland	Novartis Investigative Site	Baden
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative site	Geneve
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative site	Sion
Switzerland	Novartis Investigative Site	Zuerich
United Kingdom	Novartis Investigative Site	Aberdeen
United Kingdom	Novartis Investigative site	Chorley
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Kent
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Middx
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Penarth
United Kingdom	Novartis Investigative site	Reading-Berkshire

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Brazil,  Czechia,  Denmark,  Finland,  Germany,  Hungary,  Iceland,  Italy,  Norway,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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