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

Phase 3

Completed

• Conditions: Paget's Disease of Bone
• Interventions: Drug: Zoledronic Acid; Drug: Risedronate; Drug: Placebo to Risedronate; Drug: Placebo to Zoledronic Acid; Dietary Supplement: Calcium and Vitamin D

• Registration Number: NCT00051636
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2001-01
• Study First Submitted: 2003-01-14
• Study First Submitted QC: 2003-01-14
• Study First Posted: 2003-01-15
• Primary Completion: 2004-03
• Study Completion: 2011-04
• Results First Submitted: 2012-04-05
• Results First Submitted QC: 2012-04-05
• Status Verified: 2012-05
• Results First Posted: 2012-05-07
• Last Update Submitted: 2012-05-09
• Last Update Posted: 2012-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 172

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zoledronic Acid and Placebo to Risedronate	Zoledronic Acid	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.
Zoledronic Acid and Placebo to Risedronate	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.
Zoledronic Acid and Placebo to Risedronate	Calcium and Vitamin D	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.
Risedronate and Placebo to Zoledronic Acid	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.
Risedronate and Placebo to Zoledronic Acid	Calcium and Vitamin D	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.
Risedronate and Placebo to Zoledronic Acid	Risedronate	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.

Primary Outcome Measures

Name	Time	Method
Number of Patients Who Achieve Therapeutic Response at 6 Months.	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

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

Trial Locations

Locations (3)

Novartis Investigative Site; 🇬🇧 Vale of Glamorgan, United Kingdom

Novartis investigative site; 🇬🇧 Pernarth, United Kingdom

Novartis Investigative site; 🇬🇧 Penarth, United Kingdom