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

Paget's Disease of Bone Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00103740
• Other study ID #: CZOL446H2305
• Secondary ID: ZOL446K2305
• Status: Completed
• Phase: Phase 3
• First received: February 14, 2005
• Last updated: May 29, 2012
• Start date: April 2002
• Est. completion date: April 2011

Study information

• Verified date: May 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationNew Zealand: MedsafeAustralia: Department of Health and Ageing Therapeutic Goods AdministrationSpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyEuropean Union: European Medicines AgencyBelgium: Federal Agency for Medicines and Health Products, FAMHPSouth Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00051649

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. completion date: April 2011
• Est. primary completion date: December 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bone Diseases
• Osteitis Deformans
• Paget's Disease of Bone

Intervention

Drug:
• zoledronic acid
5 mg zoledronic acid in 5 mL of sterile water for infusion
• placebo to zoledronic acid
5 mL of sterile water for infusion
• Risedronate
30mg oral tablets overencapsulated to match the placebo capsules
• Placebo to risedronate
oral capsules
• Calcium and vitamin D supplements
Calcium and vitamin D supplements were supplied

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Fitzroy
Australia	Novartis Investigative Site	Kogarah
Australia	Novartis Investigative site	Newcastle
Australia	Novartis Investigative Site	Parkville
Australia	Novartis Investigative site	St. Leonards
Belgium	Novartis Investigative site	Brussels
Belgium	Novartis Investigative Site	Gent
Canada	Novartis Investigative Site	Montreal
France	Novartis Investigative Site	Angers
France	Novartis Investigative Site	Dreux Cedex
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Nice Cedex
France	Novartis Investigative Site	Paris Cedex
France	Novartis Investigative Site	Rouen Cedex
France	Novartis Investigative Site	Toulouse
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leverkusen
Germany	Novartis Investigative Site	Wirzburg
New Zealand	Novartis Investigative site	Christchurch
South Africa	Novartis Investigative site	Cape Town
Spain	Novartis Investigative site	Barcelona
Spain	Novartis Investigative site	Madrid
Spain	Novartis Investigative Site	Malaga
Spain	Novartis Investigative Site	Salamanca
Spain	Novartis Investigative site	Santiago de Compostela
Spain	Novartis Investigative Site	Valencia
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative site	Oxford
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Columbia	South Carolina
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	Medford	Oregon
United States	Novartis Investigative Site	New Orleans	Louisiana
United States	Novartis Investigative Site	Syracuse	New York
United States	Novartis Investigative site	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  New Zealand,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, 6 months	No
Secondary	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.	Baseline and 28 days	No
Secondary	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.	Baseline and day 10	No
Secondary	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.	Baseline and day 10	No
Secondary	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.	182 days	No
Secondary	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).	Day 28	No
Secondary	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.	Baseline and day 182	No
Secondary	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.	Baseline and day 182	No
Secondary	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.	8 years was the maximum	No
Secondary	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.	8 years was the maximum	No
Secondary	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.	8 years was maximum	No