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

Primary Purpose

Paget's Disease of Bone

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
zoledronic acid
placebo to zoledronic acid
Risedronate
Placebo to risedronate
Calcium and vitamin D supplements
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paget's Disease of Bone focused on measuring Zoledronic acid, risedronate, Paget's disease of bone

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative site
  • Novartis Investigative Site
  • Novartis Investigative site
  • Novartis Investigative site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative site
  • Novartis Investigative site
  • Novartis Investigative site
  • Novartis Investigative site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Zoledronic acid and placebo to risedronate

Risedronate and placebo to zoledronic acid

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Relative Change in Urine α-CTx in ug/mmol at Day 10
The percent change in urine α-CTx from baseline to Day 10 was measured.
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.
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).
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.
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.
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.
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.
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.

Full Information

First Posted
February 14, 2005
Last Updated
May 29, 2012
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00103740
Brief Title
Safety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget's Disease of Bone, Including an Extended Observation Period
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
April 2002 (undefined)
Primary Completion Date
December 2003 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paget's Disease of Bone
Keywords
Zoledronic acid, risedronate, Paget's disease of bone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
185 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zoledronic acid and placebo to risedronate
Arm Type
Experimental
Arm Description
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.
Arm Title
Risedronate and placebo to zoledronic acid
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Intervention Description
5 mg zoledronic acid in 5 mL of sterile water for infusion
Intervention Type
Drug
Intervention Name(s)
placebo to zoledronic acid
Intervention Description
5 mL of sterile water for infusion
Intervention Type
Drug
Intervention Name(s)
Risedronate
Intervention Description
30mg oral tablets overencapsulated to match the placebo capsules
Intervention Type
Drug
Intervention Name(s)
Placebo to risedronate
Intervention Description
oral capsules
Intervention Type
Drug
Intervention Name(s)
Calcium and vitamin D supplements
Intervention Description
Calcium and vitamin D supplements were supplied
Primary Outcome Measure Information:
Title
Number of Patients Who Had Therapeutic Response at 6 Months
Description
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.
Time Frame
Baseline, 6 months
Secondary Outcome Measure Information:
Title
Relative Change in Serum Alkaline Phosphatase in U/L at Day 28
Description
The percent change in serum alkaline phosphatase from baseline to Day 28 was measured.
Time Frame
Baseline and 28 days
Title
Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10
Description
The percent change in serum C-telopeptide from baseline to Day 10 was measured.
Time Frame
Baseline and day 10
Title
Relative Change in Urine α-CTx in ug/mmol at Day 10
Description
The percent change in urine α-CTx from baseline to Day 10 was measured.
Time Frame
Baseline and day 10
Title
Time to First Therapeutic Response
Description
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.
Time Frame
182 days
Title
Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28
Description
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).
Time Frame
Day 28
Title
Change in Pain Severity at Day 182
Description
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.
Time Frame
Baseline and day 182
Title
Change in Pain Interference at Day 182
Description
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.
Time Frame
Baseline and day 182
Title
Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period
Description
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.
Time Frame
8 years was the maximum
Title
Number of Participants With a Partial Disease Relapse During the Extended Observation Period
Description
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.
Time Frame
8 years was the maximum
Title
Number of Participants With a Disease Relapse During the Extended Observation Period
Description
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.
Time Frame
8 years was maximum

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85732
Country
United States
Facility Name
Novartis Investigative Site
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80901
Country
United States
Facility Name
Novartis Investigative Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Novartis Investigative Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Novartis Investigative Site
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Novartis Investigative Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Novartis Investigative Site
City
Medford
State/Province
Oregon
ZIP/Postal Code
97504
Country
United States
Facility Name
Novartis Investigative Site
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29209
Country
United States
Facility Name
Novartis Investigative Site
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53592
Country
United States
Facility Name
Novartis Investigative Site
City
Fitzroy
Country
Australia
Facility Name
Novartis Investigative Site
City
Kogarah
Country
Australia
Facility Name
Novartis Investigative site
City
Newcastle
Country
Australia
Facility Name
Novartis Investigative Site
City
Parkville
Country
Australia
Facility Name
Novartis Investigative site
City
St. Leonards
Country
Australia
Facility Name
Novartis Investigative site
City
Brussels
Country
Belgium
Facility Name
Novartis Investigative Site
City
Gent
Country
Belgium
Facility Name
Novartis Investigative Site
City
Montreal
Country
Canada
Facility Name
Novartis Investigative Site
City
Angers
Country
France
Facility Name
Novartis Investigative Site
City
Dreux Cedex
Country
France
Facility Name
Novartis Investigative Site
City
Marseille
Country
France
Facility Name
Novartis Investigative Site
City
Nice Cedex
Country
France
Facility Name
Novartis Investigative Site
City
Paris Cedex
Country
France
Facility Name
Novartis Investigative Site
City
Rouen Cedex
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse
Country
France
Facility Name
Novartis Investigative Site
City
Berlin
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
Country
Germany
Facility Name
Novartis Investigative Site
City
Leverkusen
Country
Germany
Facility Name
Novartis Investigative Site
City
Wirzburg
Country
Germany
Facility Name
Novartis Investigative site
City
Christchurch
Country
New Zealand
Facility Name
Novartis Investigative site
City
Cape Town
Country
South Africa
Facility Name
Novartis Investigative site
City
Barcelona
Country
Spain
Facility Name
Novartis Investigative site
City
Madrid
Country
Spain
Facility Name
Novartis Investigative Site
City
Malaga
Country
Spain
Facility Name
Novartis Investigative Site
City
Salamanca
Country
Spain
Facility Name
Novartis Investigative site
City
Santiago de Compostela
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
Country
Spain
Facility Name
Novartis Investigative Site
City
Liverpool
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
Country
United Kingdom
Facility Name
Novartis Investigative site
City
Oxford
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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