Safety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget's Disease of Bone, Including an Extended Observation Period

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

ClinicalTrials.gov Identifier:

NCT00051636

First received: January 14, 2003

Last updated: May 9, 2012

Last verified: May 2012

History of Changes

Tracking Information
First Received Date ^ICMJE	January 14, 2003
Last Updated Date	May 9, 2012
Start Date ^ICMJE	January 2001
Primary Completion Date	March 2004 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: May 9, 2012)	Number of Patients Who Achieve Therapeutic Response at 6 Months. [ Time Frame: 6 months ] [ Designated as safety issue: No ] Therapeutic response is defined as a reduction of at least 75% from baseline (Visit 1) in total serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase at the end of six months.
Original Primary Outcome Measures ^ICMJE (submitted: June 23, 2005)	Efficacy (The primary efficacy objective of this trial was to compare zoledronic acid to the active control, risedronate, with respect to the proportion of patients who achieved therapeutic response.)
Change History	Complete list of historical versions of study NCT00051636 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: May 9, 2012)	Relative Change in Serum Alkaline Phosphatase (SAP) in Units Per Liter (U/L) at Day 28 [ Time Frame: Baseline and day 28 ] [ Designated as safety issue: No ] The percent change in serum alkaline phosphatase from baseline to day 28 was measured. Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10 [ Time Frame: Baseline and day 10 ] [ Designated as safety issue: No ] The percent change in serum C-telopeptide from baseline to day 10 was measured. Relative Change in Urine Alpha C-telopeptide (α-CTx) in ug/mmol at Day 10 [ Time Frame: Baseline and day 10 ] [ Designated as safety issue: No ] The percent change in urine alpha C-telopeptide from baseline to day 10 was measured. Time to First Therapeutic Response [ Time Frame: 182 days ] [ Designated as safety issue: No ] A therapeutic response was defined as a reduction of at least 75% from baseline (Visit 1) in serum alkaline phosphatase excess (difference between measured level and midpoint to the normal range) or normalization of serum alkaline phosphatase. Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28 Relative to Baseline [ Time Frame: Baseline and day 28 ] [ Designated as safety issue: No ] Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range. Change in Pain Severity Score [ Time Frame: Baseline and day 182 ] [ Designated as safety issue: No ] 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. Change in Pain Interference Score [ Time Frame: Baseline and day 182 ] [ Designated as safety issue: No ] 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. Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period [ Time Frame: 8 years was the maximum ] [ Designated as safety issue: No ] 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. Number of Participants With a Partial Disease Relapse During the Extended Observation Period [ Time Frame: 8 years was the maximum ] [ Designated as safety issue: No ] 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. Number of Participants With a Disease Relapse During the Extended Observation Period [ Time Frame: 8 years was the maximum ] [ Designated as safety issue: No ] 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.
Original Secondary Outcome Measures ^ICMJE (submitted: June 23, 2005)	Efficacy, safety, quality of life
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	Safety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget's Disease of Bone, Including an Extended Observation Period
Official Title ^ICMJE	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 Observational Period
Brief Summary	The core study looked at the effect of Zoledronic Acid given once as an intravenous (i.v.) infusion compared to 60 days of oral Risedronate in patients with Paget's disease of bone. The effect was demonstrated in the reduction of serum alkaline phosphatase (SAP). The extended observation period included participants of the core study who responded to treatment.
Detailed Description	Not Provided
Study Type ^ICMJE	Interventional
Study Phase	Phase 3
Study Design ^ICMJE	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Condition ^ICMJE	Paget's Disease of Bone
Intervention ^ICMJE	Drug: Zoledronic Acid Zoledronic acid 5 mg in 5 mL of sterile water intravenous infusion. Other Name: Reclast, Aclasta Drug: Risedronate Oral risedronate 30 mg capsules. Other Name: Actonel Drug: Placebo to Risedronate Oral placebo of risedronate capsules. Drug: Placebo to Zoledronic Acid 5 mL of sterile water one dose intravenous infusion. Dietary Supplement: Calcium and Vitamin D Calcium and vitamin D supplements were supplied.
Study Arm (s)	Experimental: Zoledronic Acid and Placebo to Risedronate Participants received zoledronic acid 5 mg intravenous infusion one dose, 60 days of oral placebo to risedronate, calcium 500 mg twice a day and vitamin D 400 to 1000 international units daily during the core period, and received only calcium and vitamin D supplements during the extended observation period. Interventions: Drug: Zoledronic Acid Drug: Placebo to Risedronate Dietary Supplement: Calcium and Vitamin D Active Comparator: Risedronate and Placebo to Zoledronic Acid Participants received 60 days of oral risedronate 30 mg, one intravenous infusion of placebo to zoledronic acid, calcium 500 mg twice a day and vitamin D 400 to 1000 international units daily during the core period, and received only calcium and vitamin D supplements during the extended observation period. Interventions: Drug: Risedronate Drug: Placebo to Zoledronic Acid Dietary Supplement: Calcium and Vitamin D
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Completed
Enrollment ^ICMJE	172
Completion Date	April 2011
Primary Completion Date	March 2004 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	Inclusion Criteria: 30 years or older Serum alkaline phosphatase (SAP) 2 times upper limit normal (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 Exclusion Criteria: Allergic reaction to bisphosphonates History of upper gastrointestinal disorders History of iritis, uveitis Calculated creatinine clearance < 30 ml/min at baseline Evidence of vitamin D deficiency Other protocol-defined inclusion/exclusion criteria applied.
Gender	Both
Ages	30 Years and older
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	United States, Australia, Canada, New Zealand, Spain, United Kingdom

Administrative Information
NCT Number ^ICMJE	NCT00051636
Other Study ID Numbers ^ICMJE	CZOL446H2304, ZOL446K2304
Has Data Monitoring Committee	Not Provided
Responsible Party	Novartis ( Novartis Pharmaceuticals )
Study Sponsor ^ICMJE	Novartis Pharmaceuticals
Collaborators ^ICMJE	Not Provided
Investigators ^ICMJE	Not Provided
Information Provided By	Novartis
Verification Date	May 2012
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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