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:
NCT00051636
First received: January 14, 2003
Last updated: May 9, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Paget's Disease of Bone
Drug: Zoledronic Acid
Drug: Risedronate
Drug: Placebo to Risedronate
Drug: Placebo to Zoledronic Acid
Dietary Supplement: Calcium and Vitamin D
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 Observational Period

Resource links provided by NLM:


Further study details as provided by Novartis:

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

  • Time to First Therapeutic Response [ Time Frame: 182 days ] [ 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 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 [ Time Frame: Baseline and day 28 ] [ Designated as safety issue: No ]
    Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range.

  • Change in Pain Severity Score [ 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 Score [ 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 the 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: 172
Study Start Date: January 2001
Study Completion Date: April 2011
Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zoledronic Acid and Placebo to Risedronate
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.
Drug: Zoledronic Acid
Zoledronic acid 5 mg in 5 mL of sterile water intravenous infusion.
Other Name: Reclast, Aclasta
Drug: Placebo to Risedronate
Oral placebo of risedronate capsules.
Dietary Supplement: Calcium and Vitamin D
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 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.
Drug: Risedronate
Oral risedronate 30 mg capsules.
Other Name: Actonel
Drug: 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.

  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
  • 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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00051636

  Show 34 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00051636     History of Changes
Obsolete Identifiers: NCT00050258
Other Study ID Numbers: CZOL446H2304, ZOL446K2304
Study First Received: January 14, 2003
Results First Received: April 5, 2012
Last Updated: May 9, 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

Keywords provided by Novartis:
Bisphosphonate
SAP
SAP excess
non-inferiority
therapeutic response
extended observation period

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 July 24, 2014