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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
Risedronate
Placebo to Risedronate
Placebo to Zoledronic Acid
Calcium and Vitamin D
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 Bisphosphonate, SAP, SAP excess, non-inferiority, therapeutic response, extended observation period

Eligibility Criteria

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

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.

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

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 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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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 Alpha C-telopeptide (α-CTx) in ug/mmol at Day 10
The percent change in urine alpha C-telopeptide from baseline to day 10 was measured.
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.
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.
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.
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.
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
January 14, 2003
Last Updated
May 9, 2012
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00051636
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 Observational Period
Study Type
Interventional

2. Study Status

Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
January 2001 (undefined)
Primary Completion Date
March 2004 (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 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.

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
Bisphosphonate, SAP, SAP excess, non-inferiority, therapeutic response, extended observation period

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Zoledronic Acid and Placebo to Risedronate
Arm Type
Experimental
Arm Description
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.
Arm Title
Risedronate and Placebo to Zoledronic Acid
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Zoledronic Acid
Other Intervention Name(s)
Reclast, Aclasta
Intervention Description
Zoledronic acid 5 mg in 5 mL of sterile water intravenous infusion.
Intervention Type
Drug
Intervention Name(s)
Risedronate
Other Intervention Name(s)
Actonel
Intervention Description
Oral risedronate 30 mg capsules.
Intervention Type
Drug
Intervention Name(s)
Placebo to Risedronate
Intervention Description
Oral placebo of risedronate capsules.
Intervention Type
Drug
Intervention Name(s)
Placebo to Zoledronic Acid
Intervention Description
5 mL of sterile water one dose intravenous infusion.
Intervention Type
Dietary Supplement
Intervention Name(s)
Calcium and Vitamin D
Intervention Description
Calcium and vitamin D supplements were supplied.
Primary Outcome Measure Information:
Title
Number of Patients Who Achieve Therapeutic Response at 6 Months.
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Relative Change in Serum Alkaline Phosphatase (SAP) in Units Per Liter (U/L) at Day 28
Description
The percent change in serum alkaline phosphatase from baseline to day 28 was measured.
Time Frame
Baseline and day 28
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 Alpha C-telopeptide (α-CTx) in ug/mmol at Day 10
Description
The percent change in urine alpha C-telopeptide from baseline to day 10 was measured.
Time Frame
Baseline and day 10
Title
Time to First Therapeutic Response
Description
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.
Time Frame
182 days
Title
Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28 Relative to Baseline
Description
Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range.
Time Frame
Baseline and day 28
Title
Change in Pain Severity Score
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 Score
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 the maximum

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Novartis Investigative Site
City
Santa Monica
State/Province
California
ZIP/Postal Code
90414
Country
United States
Facility Name
Novartis Investigative Site
City
Lakewood
State/Province
Colorado
ZIP/Postal Code
80227
Country
United States
Facility Name
Novartis Investigative Site
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33433
Country
United States
Facility Name
Novartis Investigative Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33101
Country
United States
Facility Name
Novartis Investigative site
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Novartis investigative site
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01601
Country
United States
Facility Name
Novartis investigative site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48021
Country
United States
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
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
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
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
Providence
State/Province
Rhode Island
ZIP/Postal Code
02908
Country
United States
Facility Name
Novartis Investigative Site
City
Concord
Country
Australia
Facility Name
Novartis Investigative Site
City
Fitzroy
Country
Australia
Facility Name
Novartis Investigative site
City
Geelong
Country
Australia
Facility Name
Novartis Investigative Site
City
Kogarah
Country
Australia
Facility Name
Novartis Investigative site
City
Maroochydore
Country
Australia
Facility Name
Novartis Investigative site
City
Nedlands
Country
Australia
Facility Name
Novartis Investigative Site
City
Calgary
Country
Canada
Facility Name
Novartis Investigative Site
City
London
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
Country
Canada
Facility Name
Novartis Investigative Site
City
Ste-Foy
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
Country
Canada
Facility Name
Novartis Investigative site
City
Auckland
Country
New Zealand
Facility Name
Novartis Investigative Site
City
Christchurch
Country
New Zealand
Facility Name
Novartis Investigative site
City
Salamanca
Country
Spain
Facility Name
Novartis Investigative site
City
Liverpool
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Manchester
Country
United Kingdom
Facility Name
Novartis Investigative site
City
Nottingham
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Oxford
Country
United Kingdom
Facility Name
Novartis Investigative site
City
Penarth
Country
United Kingdom
Facility Name
Novartis investigative site
City
Pernarth
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Stanmore
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Vale of Glamorgan
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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