Paget's Disease of BonePhase 3NCT00103740
Safety and Efficacy Trial With Zoledronic Acid for the Treatment of Paget's Disease of Bone, Including an Extended Observation Period
A Phase 3 study testing zoledronic acid, Risedronate and Calcium and vitamin D supplements in people with Paget's Disease of Bone, run by Novartis Pharmaceuticals at 41 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Paget's Disease of Bone
- What is being tested?
- zoledronic acid, Risedronate and Calcium and vitamin D supplements
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 185 participants
- Where
- 41 sitesin 10 countries
- Study dates
- Apr 2002to Apr 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
41 sites in 10 countries.
41 sites in 10 countries
United States10 sites
Novartis Investigative Site
Boston, Massachusetts, 02114
Novartis Investigative Site
Cleveland, Ohio, 44195
Novartis Investigative Site
Colorado Springs, Colorado, 80901
Novartis Investigative Site
Columbia, South Carolina, 29209
Novartis Investigative Site
Indianapolis, Indiana, 46202
Novartis Investigative Site
Madison, Wisconsin, 53592
Novartis Investigative Site
Medford, Oregon, 97504
Novartis Investigative Site
New Orleans, Louisiana, 70121
Novartis Investigative Site
Syracuse, New York, 13210
Novartis Investigative site
Tucson, Arizona, 85732
France7 sites
Novartis Investigative Site
Angers
Novartis Investigative Site
Dreux
Novartis Investigative Site
Marseille
Novartis Investigative Site
Nice
Novartis Investigative Site
Paris
Novartis Investigative Site
Rouen
Novartis Investigative Site
Toulouse
Spain6 sites
Novartis Investigative site
Barcelona
Novartis Investigative site
Madrid
Novartis Investigative Site
Málaga
Novartis Investigative Site
Salamanca
Novartis Investigative site
Santiago de Compostela
Novartis Investigative Site
Valencia
Australia5 sites
Novartis Investigative Site
Fitzroy
Novartis Investigative Site
Kogarah
Novartis Investigative site
Newcastle
Novartis Investigative Site
Parkville
Novartis Investigative site
St Leonards
Germany5 sites
Novartis Investigative Site
Berlin
Novartis Investigative Site
Frankfurt
Novartis Investigative Site
Leipzig
Novartis Investigative Site
Leverkusen
Novartis Investigative Site
Wirzburg
United Kingdom3 sites
Novartis Investigative Site
Liverpool
Novartis Investigative Site
London
Novartis Investigative site
Oxford
Belgium2 sites
Novartis Investigative site
Brussels
Novartis Investigative Site
Ghent
About this study
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
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
- Being tested
- zoledronic acid, placebo to zoledronic acid, Risedronate, Placebo to risedronate, Calcium and vitamin D supplements
- Keywords
- Zoledronic acid, risedronate, Paget's disease of bone
- Medical subject headings
- Osteitis Deformans
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zoledronic acidDrug
5 mg zoledronic acid in 5 mL of sterile water for infusion
placebo to zoledronic acidDrug
5 mL of sterile water for infusion
RisedronateDrug
30mg oral tablets overencapsulated to match the placebo capsules
Placebo to risedronateDrug
oral capsules
Calcium and vitamin D supplementsDrug
Calcium and vitamin D supplements were supplied
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: placebo to zoledronic acid; Drug: Risedronate; Drug: Calcium and vitamin D supplements |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 6 months
Secondary outcomes (10)
Relative Change in Serum Alkaline Phosphatase in U/L at Day 28
The percent change in serum alkaline phosphatase from baseline to Day 28 was measured.
Measured: Baseline and 28 days
Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10
The percent change in serum C-telopeptide from baseline to Day 10 was measured.
Measured: Baseline and day 10
Relative Change in Urine α-CTx in ug/mmol at Day 10
The percent change in urine α-CTx from baseline to Day 10 was measured.
Measured: Baseline and day 10
Time to First Therapeutic Response
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.
Measured: 182 days
Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28
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).
Measured: Day 28
Change in Pain Severity at 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.
Measured: Baseline and day 182
Change in Pain Interference at 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.
Measured: Baseline and day 182
Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period
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.
Measured: 8 years was the maximum
Number of Participants With a Partial Disease Relapse During the Extended Observation Period
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.
Measured: 8 years was the maximum
Number of Participants With a Disease Relapse During the Extended Observation Period
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.
Measured: 8 years was maximum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2005 (estimated)
- Study startApr 2002
- Primary completionDec 2003
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Paget's Disease of BoneStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 185 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00103740
- Sponsor's protocol ID
- CZOL446H2305
- Other IDs
- ZOL446K2305
- Status last verified
- May 2012
- First submitted
- 14 Feb 2005
- Last updated
- 4 Jun 2012
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00103740
- Acronym / sponsor ID
- CZOL446H2305
- Conditions
- Paget's Disease of Bone
- Keywords
- Zoledronic acid, risedronate, Paget's disease of bone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 185 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2002
- Primary completion
- Dec 2003 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 15 Feb 2005 (estimated)
- Results
- Posted 2 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zoledronic acid and placebo to risedronate | Experimental | Drug: zoledronic acid, Drug: Placebo to risedronate, Drug: Calcium and vitamin D supplementsParticipants 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. |
| Risedronate and placebo to zoledronic acid | Active comparator | Drug: placebo to zoledronic acid, Drug: Risedronate, Drug: Calcium and vitamin D supplementsParticipants 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. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zoledronic acid5 mg zoledronic acid in 5 mL of sterile water for infusion | Drug | Zoledronic acid and placebo to risedronate |
| placebo to zoledronic acid5 mL of sterile water for infusion | Drug | Risedronate and placebo to zoledronic acid |
| Risedronate30mg oral tablets overencapsulated to match the placebo capsules | Drug | Risedronate and placebo to zoledronic acid |
| Placebo to risedronateoral capsules | Drug | Zoledronic acid and placebo to risedronate |
| Calcium and vitamin D supplementsCalcium and vitamin D supplements were supplied | Drug | Risedronate and placebo to zoledronic acid, Zoledronic acid and placebo to risedronate |
Primary outcome
Number of Patients Who Had Therapeutic Response at 6 Months
Time frame: Baseline, 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.
10 secondary outcomes
Relative Change in Serum Alkaline Phosphatase in U/L at Day 28
Time frame: Baseline and 28 days
Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10
Time frame: Baseline and day 10
Relative Change in Urine α-CTx in ug/mmol at Day 10
Time frame: Baseline and day 10
Time to First Therapeutic Response
Time frame: 182 days
Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28
Time frame: Day 28
Change in Pain Severity at Day 182
Time frame: Baseline and day 182
Change in Pain Interference at Day 182
Time frame: Baseline and day 182
Number of Participants With a Loss of Therapeutic Response During the Extended Observation Period
Time frame: 8 years was the maximum
Number of Participants With a Partial Disease Relapse During the Extended Observation Period
Time frame: 8 years was the maximum
Number of Participants With a Disease Relapse During the Extended Observation Period
Time frame: 8 years was maximum
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
41 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing zoledronic acid, Risedronate and Calcium and vitamin D supplements in people with Paget's Disease of Bone, run by Novartis Pharmaceuticals at 41 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, France, Spain, Australia, Germany and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 May 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Who Had Therapeutic Response at 6 Months (time frame: Baseline, 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2012.