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

NCT00103740 | Completed Phase 3 Results

• 2 other identifiers: CZOL446H2305ZOL446K2305
• Study Type: interventional
• Target: 185
• Locations: 10 countries
• Sites: 41

Brief Summary

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.

Conditions

Paget's Disease of Bone

Keywords

Zoledronic acid, risedronate, Paget's disease of bone

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Had Therapeutic Response at 6 Months

  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.

  Baseline, 6 months

Secondary Outcomes (10)

• Relative Change in Serum Alkaline Phosphatase in U/L at Day 28

  Baseline and 28 days

• Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10

  Baseline and day 10

• Relative Change in Urine α-CTx in ug/mmol at Day 10

  Baseline and day 10

• Time to First Therapeutic Response

  182 days

• Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28

  Day 28

Study Arms (2)

Zoledronic acid and placebo to risedronate

EXPERIMENTAL

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; Drug: Placebo to risedronate; Drug: Calcium and vitamin D supplements

Risedronate and placebo to zoledronic acid

ACTIVE COMPARATOR

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; Drug: Risedronate; Drug: Calcium and vitamin D supplements

Interventions

zoledronic acid DRUG

5 mg zoledronic acid in 5 mL of sterile water for infusion

Zoledronic acid and placebo to risedronate

placebo to zoledronic acid DRUG

5 mL of sterile water for infusion

Risedronate and placebo to zoledronic acid

Risedronate DRUG

30mg oral tablets overencapsulated to match the placebo capsules

Risedronate and placebo to zoledronic acid

Placebo to risedronate DRUG

oral capsules

Zoledronic acid and placebo to risedronate

Calcium and vitamin D supplements DRUG

Calcium and vitamin D supplements were supplied

Risedronate and placebo to zoledronic acid; Zoledronic acid and placebo to risedronate

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.).
• days washout calcitonin
• day washout bisphosphonate

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (41)

Novartis Investigative site

Tucson, Arizona, 85732, United States

Location

Novartis Investigative Site

Colorado Springs, Colorado, 80901, United States

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Indianapolis, Indiana, 46202, United States

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New Orleans, Louisiana, 70121, United States

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Novartis Investigative Site

Boston, Massachusetts, 02114, United States

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Syracuse, New York, 13210, United States

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Cleveland, Ohio, 44195, United States

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Medford, Oregon, 97504, United States

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Columbia, South Carolina, 29209, United States

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Madison, Wisconsin, 53592, United States

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Fitzroy, Australia

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Kogarah, Australia

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Newcastle, Australia

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Parkville, Australia

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St Leonards, Australia

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Brussels, Belgium

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Ghent, Belgium

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Montreal, Canada

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Angers, France

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Dreux, France

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Marseille, France

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Nice, France

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Paris, France

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Rouen, France

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Toulouse, France

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Berlin, Germany

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Frankfurt, Germany

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Leipzig, Germany

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Leverkusen, Germany

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Wirzburg, Germany

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Christchurch, New Zealand

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Cape Town, South Africa

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Barcelona, Spain

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Madrid, Spain

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Málaga, Spain

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Salamanca, Spain

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Santiago de Compostela, Spain

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Novartis Investigative Site

Valencia, Spain

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Novartis Investigative Site

Liverpool, United Kingdom

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Novartis Investigative Site

London, United Kingdom

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Novartis Investigative site

Oxford, United Kingdom

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MeSH Terms

Conditions

Osteitis Deformans

Interventions

Zoledronic Acid; Risedronic Acid; Calcium

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridines; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2005
• First Posted: February 15, 2005
• Study Start: April 1, 2002
• Primary Completion: December 1, 2003
• Study Completion: April 1, 2011
• Last Updated: June 4, 2012
• Results First Posted: May 2, 2012

Record last verified: 2012-05

Locations

FR (7); US (10); NZ (1); ZA (1); AU (5); BE (2); CA (1); ES (6); GB (3); DE (5)