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 Observational Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00051636
• Other study ID #: CZOL446H2304
• Secondary ID: ZOL446K2304
• Status: Completed
• Phase: Phase 3
• First received: January 14, 2003
• Last updated: May 9, 2012
• Start date: January 2001
• 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 Agency
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00050258

Recruitment information / eligibility

• Status: Completed
• Enrollment: 172
• Est. completion date: April 2011
• Est. primary completion date: March 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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.

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
Zoledronic acid 5 mg in 5 mL of sterile water intravenous infusion.
• Risedronate
Oral risedronate 30 mg capsules.
• Placebo to Risedronate
Oral placebo of risedronate capsules.
• 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.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Concord
Australia	Novartis Investigative Site	Fitzroy
Australia	Novartis Investigative site	Geelong
Australia	Novartis Investigative Site	Kogarah
Australia	Novartis Investigative site	Maroochydore
Australia	Novartis Investigative site	Nedlands
Canada	Novartis Investigative Site	Calgary
Canada	Novartis Investigative Site	London
Canada	Novartis Investigative Site	Montreal
Canada	Novartis Investigative Site	Ste-Foy
Canada	Novartis Investigative Site	Toronto
New Zealand	Novartis Investigative site	Auckland
New Zealand	Novartis Investigative Site	Christchurch
Spain	Novartis Investigative site	Salamanca
United Kingdom	Novartis Investigative site	Liverpool
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative site	Nottingham
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative site	Penarth
United Kingdom	Novartis investigative site	Pernarth
United Kingdom	Novartis Investigative Site	Stanmore
United Kingdom	Novartis Investigative Site	Vale of Glamorgan
United States	Novartis Investigative Site	Boca Raton	Florida
United States	Novartis investigative site	Detroit	Michigan
United States	Novartis investigative site	Durham	North Carolina
United States	Novartis Investigative Site	Lakewood	Colorado
United States	Novartis Investigative site	Maywood	Illinois
United States	Novartis investigative site	Medford	Oregon
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	New York	New York
United States	Novartis investigative site	Providence	Rhode Island
United States	Novartis Investigative Site	Santa Monica	California
United States	Novartis investigative site	Syracuse	New York
United States	Novartis investigative site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients Who Achieve Therapeutic Response at 6 Months.	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.	6 months	No
Secondary	Relative Change in Serum Alkaline Phosphatase (SAP) in Units Per Liter (U/L) at Day 28	The percent change in serum alkaline phosphatase from baseline to day 28 was measured.	Baseline and day 28	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 Alpha C-telopeptide (a-CTx) in ug/mmol at Day 10	The percent change in urine alpha C-telopeptide from baseline to day 10 was measured.	Baseline and day 10	No
Secondary	Time to First Therapeutic Response	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.	182 days	No
Secondary	Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28 Relative to Baseline	Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range.	Baseline and day 28	No
Secondary	Change in Pain Severity Score	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 Score	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 the maximum	No