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:
NCT00103740
First received: February 14, 2005
Last updated: May 29, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Paget's Disease of Bone
Drug: zoledronic acid
Drug: placebo to zoledronic acid
Drug: Risedronate
Drug: Placebo to risedronate
Drug: Calcium and vitamin D supplements
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Patients Who Had Therapeutic Response at 6 Months [ Time Frame: Baseline, 6 months ] [ 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 (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 [ Time Frame: Baseline and 28 days ] [ 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 α-CTx in ug/mmol at Day 10 [ Time Frame: Baseline and day 10 ] [ Designated as safety issue: No ]
    The percent change in urine α-CTx from baseline to Day 10 was measured.

  • Time to First Therapeutic Response [ Time Frame: 182 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    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 [ 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 at Day 182 [ 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 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.


Enrollment: 185
Study Start Date: April 2002
Study Completion Date: April 2011
Primary Completion Date: December 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zoledronic acid and placebo to risedronate
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.
Drug: zoledronic acid
5 mg zoledronic acid in 5 mL of sterile water for infusion
Drug: Placebo to risedronate
oral capsules
Drug: Calcium and vitamin D supplements
Calcium and vitamin D supplements were supplied
Active Comparator: Risedronate and placebo to zoledronic acid
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.
Drug: placebo to zoledronic acid
5 mL of sterile water for infusion
Drug: Risedronate
30mg oral tablets overencapsulated to match the placebo capsules
Drug: Calcium and vitamin D supplements
Calcium and vitamin D supplements were supplied

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103740

  Show 41 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00103740     History of Changes
Obsolete Identifiers: NCT00051649
Other Study ID Numbers: CZOL446H2305, ZOL446K2305
Study First Received: February 14, 2005
Results First Received: April 5, 2012
Last Updated: May 29, 2012
Health Authority: United States: Food and Drug Administration
New Zealand: Medsafe
Australia: Department of Health and Ageing Therapeutic Goods Administration
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
European Union: European Medicines Agency
Belgium: Federal Agency for Medicines and Health Products, FAMHP
South Africa: Medicines Control Council

Keywords provided by Novartis:
Zoledronic acid, risedronate, Paget's disease of bone

Additional relevant MeSH terms:
Bone Diseases
Osteitis Deformans
Musculoskeletal Diseases
Risedronic acid
Zoledronic acid
Calcium, Dietary
Vitamin D
Ergocalciferols
Etidronic Acid
Diphosphonates
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 26, 2014