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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00103740




Trial ID
NCT00103740
Ethics application status
Date submitted
14/02/2005
Date registered
14/02/2005
Date last updated
29/05/2012

Titles & IDs
Public title
Safety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget's Disease of Bone, Including an Extended Observation Period
Scientific title
Randomized, Double-Blind, Safety and Efficacy Trial With Intravenous Zoledronic Acid for the Treatment of Paget's Disease of Bone Using Risedronate as a Comparator, Including an Extended Observation Period
Secondary ID [1] 0 0
ZOL446K2305
Secondary ID [2] 0 0
CZOL446H2305
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paget's Disease of Bone 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - zoledronic acid
Treatment: Drugs - placebo to zoledronic acid
Treatment: Drugs - Risedronate
Treatment: Drugs - Placebo to risedronate
Treatment: Drugs - Calcium and vitamin D supplements

Experimental: Zoledronic acid and placebo to risedronate - Participants received zoledronic acid 5.0 mg i.v. infusion one dose, 60 days of oral placebo to risedronate, calcium 500mg bid and vitamin D 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.

Active Comparator: Risedronate and placebo to zoledronic acid - Participants received 60 days of oral risedronate 30 mg, one i.v. infusion of placebo to zoledronic acid infusion, calcium 500mg bid and vitamin d 400 to 1000 IU daily during the core period, and received only calcium and vitamin D supplements during the extended observation period.


Treatment: Drugs: zoledronic acid
5 mg zoledronic acid in 5 mL of sterile water for infusion

Treatment: Drugs: placebo to zoledronic acid
5 mL of sterile water for infusion

Treatment: Drugs: Risedronate
30mg oral tablets overencapsulated to match the placebo capsules

Treatment: Drugs: Placebo to risedronate
oral capsules

Treatment: Drugs: Calcium and vitamin D supplements
Calcium and vitamin D supplements were supplied

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

Outcomes
Primary outcome [1] 0 0
Number of Patients Who Had Therapeutic Response at 6 Months - A therapeutic response was defined as a reduction of at least 75% from baseline (Visit 1) in serum alkaline phosphatase (SAP) excess (difference between measured level and midpoint to the normal range) or normalization of SAP at the end of six months.
Timepoint [1] 0 0
Baseline, 6 months
Secondary outcome [1] 0 0
Relative Change in Serum Alkaline Phosphatase in U/L at Day 28 - The percent change in serum alkaline phosphatase from baseline to Day 28 was measured.
Timepoint [1] 0 0
Baseline and 28 days
Secondary outcome [2] 0 0
Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10 - The percent change in serum C-telopeptide from baseline to Day 10 was measured.
Timepoint [2] 0 0
Baseline and day 10
Secondary outcome [3] 0 0
Relative Change in Urine a-CTx in ug/mmol at Day 10 - The percent change in urine a-CTx from baseline to Day 10 was measured.
Timepoint [3] 0 0
Baseline and day 10
Secondary outcome [4] 0 0
Time to First Therapeutic Response - Therapeutic response was defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase.
Timepoint [4] 0 0
182 days
Secondary outcome [5] 0 0
Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28 - Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range. Central laboratory reference ranges for serum alkaline phosphatase: 31-110 U/L (female & male 20-58 years) and 35-115 U/L (female & male >58 years).
Timepoint [5] 0 0
Day 28
Secondary outcome [6] 0 0
Change in Pain Severity at Day 182 - Change in pain severity score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain.
Timepoint [6] 0 0
Baseline and day 182
Secondary outcome [7] 0 0
Change in Pain Interference at Day 182 - Change in pain interference score from Brief Pain Inventory-Short Form (BPI-SF). This scale values are 0 to 10, a lower score means little to no pain while a higher score means greater pain.
Timepoint [7] 0 0
Baseline and day 182
Secondary outcome [8] 0 0
Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period - Extended observation period. A therapeutic response is defined as a reduction of at least 75% from baseline in serum alkaline phosphatase excess or normalization of serum alkaline phosphatase.
Timepoint [8] 0 0
8 years was the maximum
Secondary outcome [9] 0 0
Number of Participants With a Partial Disease Relapse During the Extended Observation Period - Extended observation period. A partial disease relapse was defined as an increase in serum alkaline phosphatase >= 50% from the serum alkaline phosphatase measurement at Month 6 and at least 1.25 times the upper normal limit.
Timepoint [9] 0 0
8 years was the maximum
Secondary outcome [10] 0 0
Number of Participants With a Disease Relapse During the Extended Observation Period - Extended observation period. A disease relapse was defined as the occurrence of a serum alkaline phosphatase level that was >= 80% of baseline serum alkaline phosphatase value.
Timepoint [10] 0 0
8 years was maximum

Eligibility
Key inclusion criteria
- 30 years or older

- SAP 2 times ULN

- Confirmed diagnosis of Paget's disease of the bone (by x-ray, magnetic resonance
imaging, computerized tomography, radioisotope imaging, etc.).

- 90 days washout calcitonin

- 180 day washout bisphosphonate
Minimum age
30 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Allergic reaction to bisphosphonates

- History of upper GI disorders

- History of iritis, uveitis

- Calculated creatinine clearance < 30 ml/min at baseline

- Evidence of vitamin D deficiency

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 - Fitzroy
Recruitment hospital [2] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [3] 0 0
Novartis Investigative site - Newcastle
Recruitment hospital [4] 0 0
Novartis Investigative Site - Parkville
Recruitment hospital [5] 0 0
Novartis Investigative site - St. Leonards
Recruitment postcode(s) [1] 0 0
- Fitzroy
Recruitment postcode(s) [2] 0 0
- Kogarah
Recruitment postcode(s) [3] 0 0
- Newcastle
Recruitment postcode(s) [4] 0 0
- Parkville
Recruitment postcode(s) [5] 0 0
- St. Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
South Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Wisconsin
Country [11] 0 0
Belgium
State/province [11] 0 0
Brussels
Country [12] 0 0
Belgium
State/province [12] 0 0
Gent
Country [13] 0 0
Canada
State/province [13] 0 0
Montreal
Country [14] 0 0
France
State/province [14] 0 0
Angers
Country [15] 0 0
France
State/province [15] 0 0
Dreux Cedex
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
France
State/province [17] 0 0
Nice Cedex
Country [18] 0 0
France
State/province [18] 0 0
Paris Cedex
Country [19] 0 0
France
State/province [19] 0 0
Rouen Cedex
Country [20] 0 0
France
State/province [20] 0 0
Toulouse
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Germany
State/province [22] 0 0
Frankfurt
Country [23] 0 0
Germany
State/province [23] 0 0
Leipzig
Country [24] 0 0
Germany
State/province [24] 0 0
Leverkusen
Country [25] 0 0
Germany
State/province [25] 0 0
Wirzburg
Country [26] 0 0
New Zealand
State/province [26] 0 0
Christchurch
Country [27] 0 0
South Africa
State/province [27] 0 0
Cape Town
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Spain
State/province [30] 0 0
Malaga
Country [31] 0 0
Spain
State/province [31] 0 0
Salamanca
Country [32] 0 0
Spain
State/province [32] 0 0
Santiago de Compostela
Country [33] 0 0
Spain
State/province [33] 0 0
Valencia
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Liverpool
Country [35] 0 0
United Kingdom
State/province [35] 0 0
London
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Oxford

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this core study was to show non-inferiority of zoledronic acid to
risedronate, with respect to the proportion of patients who achieved therapeutic response.
The extended observation period included participants of the core study who responded to
treatment.
Trial website
https://clinicaltrials.gov/show/NCT00103740
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
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