Paget's Disease of BonePhase 3NCT00051636
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 in people with Paget's Disease of Bone, run by Novartis Pharmaceuticals at 34 sites in 6 countries.
Trial 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). 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
- 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
- 172 participants
- Where
- 34 sitesin 6 countries
- Study dates
- Jan 2001to 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
- 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
Who cannot join
- 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.
Trial locations and contacts
34 sites in 6 countries.
34 sites in 6 countries
United States12 sites
Novartis Investigative Site
Boca Raton, Florida, 33433
Novartis investigative site
Detroit, Michigan, 48021
Novartis investigative site
Durham, North Carolina, 27710
Novartis Investigative Site
Lakewood, Colorado, 80227
Novartis Investigative site
Maywood, Illinois, 60153
Novartis investigative site
Medford, Oregon, 97504
Novartis Investigative Site
Miami, Florida, 33101
Novartis Investigative Site
New York, New York, 10029
Novartis investigative site
Providence, Rhode Island, 02908
Novartis Investigative Site
Santa Monica, California, 90414
Novartis investigative site
Syracuse, New York, 13210
Novartis investigative site
Worcester, Massachusetts, 01601
United Kingdom8 sites
Novartis Investigative site
Liverpool
Novartis Investigative Site
Manchester
Novartis Investigative site
Nottingham
Novartis Investigative Site
Oxford
Novartis Investigative site
Penarth
Novartis investigative site
Pernarth
Novartis Investigative Site
Stanmore
Novartis Investigative Site
Vale of Glamorgan
Australia6 sites
Novartis Investigative Site
Concord
Novartis Investigative Site
Fitzroy
Novartis Investigative site
Geelong
Novartis Investigative Site
Kogarah
Novartis Investigative site
Maroochydore
Novartis Investigative site
Nedlands
Canada5 sites
Novartis Investigative Site
Calgary
Novartis Investigative Site
London
Novartis Investigative Site
Montreal
Novartis Investigative Site
Ste-Foy
Novartis Investigative Site
Toronto
New Zealand2 sites
Novartis Investigative site
Auckland
Novartis Investigative Site
Christchurch
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 Observational Period
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.
- Conditions
- Paget's Disease of Bone
- Being tested
- Zoledronic Acid, Risedronate, Placebo to Risedronate, Placebo to Zoledronic Acid, Calcium and Vitamin D
- Keywords
- Bisphosphonate, SAP, SAP excess, non-inferiority, therapeutic response, extended observation period
- 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
Also called Reclast, Aclasta
Zoledronic acid 5 mg in 5 mL of sterile water intravenous infusion.
RisedronateDrug
Also called Actonel
Oral risedronate 30 mg capsules.
Placebo to RisedronateDrug
Oral placebo of risedronate capsules.
Placebo to Zoledronic AcidDrug
5 mL of sterile water one dose intravenous infusion.
Calcium and Vitamin DDietary supplement
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 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. Receives: Drug: Zoledronic Acid; Drug: Placebo to Risedronate; Dietary Supplement: Calcium and Vitamin D |
| Risedronate and Placebo to Zoledronic Acid | Active comparator | 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. Receives: Drug: Risedronate; Drug: Placebo to Zoledronic Acid; Dietary Supplement: Calcium and Vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Who Achieve Therapeutic Response at 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.
Measured: 6 months
Secondary outcomes (10)
Relative Change in Serum Alkaline Phosphatase (SAP) in Units Per Liter (U/L) at Day 28
The percent change in serum alkaline phosphatase from baseline to day 28 was measured.
Measured: Baseline and day 28
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 Alpha C-telopeptide (α-CTx) in ug/mmol at Day 10
The percent change in urine alpha C-telopeptide from baseline to day 10 was measured.
Measured: Baseline and day 10
Time to First Therapeutic Response
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.
Measured: 182 days
Number of Patients Who Achieved Serum Alkaline Phosphatase Normalization at Day 28 Relative to Baseline
Normalization of serum alkaline phosphatase occurred if the serum alkaline phosphatase measurement fell within the normal range.
Measured: Baseline and day 28
Change in Pain Severity Score
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 Score
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 the maximum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2003 (estimated)
- Study startJan 2001
- Primary completionMar 2004
- 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
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00051636
- Sponsor's protocol ID
- CZOL446H2304
- Other IDs
- ZOL446K2304
- Status last verified
- May 2012
- First submitted
- 14 Jan 2003
- Last updated
- 15 May 2012
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 May 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 Observational Period
- ClinicalTrials.gov ID
- NCT00051636
- Acronym / sponsor ID
- CZOL446H2304
- Conditions
- Paget's Disease of Bone
- Keywords
- Bisphosphonate, SAP, SAP excess, non-inferiority, therapeutic response, extended observation period
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 172 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2001
- Primary completion
- Mar 2004 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 15 Jan 2003 (estimated)
- Results
- Posted 7 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 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.
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, Dietary Supplement: Calcium and Vitamin DParticipants 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 | Active comparator | Drug: Risedronate, Drug: Placebo to Zoledronic Acid, Dietary Supplement: Calcium and Vitamin DParticipants 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. |
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
- 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
Key exclusion criteria (6 listed)
- 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
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 AcidAlso: Reclast, AclastaZoledronic acid 5 mg in 5 mL of sterile water intravenous infusion. | Drug | Zoledronic Acid and Placebo to Risedronate |
| RisedronateAlso: ActonelOral risedronate 30 mg capsules. | Drug | Risedronate and Placebo to Zoledronic Acid |
| Placebo to RisedronateOral placebo of risedronate capsules. | Drug | Zoledronic Acid and Placebo to Risedronate |
| Placebo to Zoledronic Acid5 mL of sterile water one dose intravenous infusion. | Drug | Risedronate and Placebo to Zoledronic Acid |
| Calcium and Vitamin DCalcium and vitamin D supplements were supplied. | Dietary supplement | Risedronate and Placebo to Zoledronic Acid, Zoledronic Acid and Placebo to Risedronate |
Primary outcome
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.
10 secondary outcomes
Relative Change in Serum Alkaline Phosphatase (SAP) in Units Per Liter (U/L) at Day 28
Time frame: Baseline and day 28
Relative Change in Serum C-telopeptide (CTx) in ng/mL at Day 10
Time frame: Baseline and day 10
Relative Change in Urine Alpha C-telopeptide (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 Relative to Baseline
Time frame: Baseline and day 28
Change in Pain Severity Score
Time frame: Baseline and day 182
Change in Pain Interference Score
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 the maximum
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 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.
The record lists no contact. Use the official record to reach the sponsor.
34 sites in 6 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 in people with Paget's Disease of Bone, run by Novartis Pharmaceuticals at 34 sites in 6 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 15 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States, United Kingdom, Australia, Canada, New Zealand and 1 more country. 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 7 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 Achieve Therapeutic Response at 6 Months. (time frame: 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 15 May 2012.