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

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: March 2004

Interventions

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

Arms, Groups and Cohorts

  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Number of Patients Who Achieve Therapeutic Response at 6 Months.
    • Time Frame: 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 Measures

  • Relative Change in Serum Alkaline Phosphatase (SAP) in Units Per Liter (U/L) at Day 28
    • Time Frame: Baseline and 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
    • Time Frame: Baseline and 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
    • Time Frame: Baseline and day 10
    • The percent change in urine alpha C-telopeptide from baseline to day 10 was measured.
  • Time to First Therapeutic Response
    • Time Frame: 182 days
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 30 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Novartis Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor

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