An Open Label, Reclast®/Aclasta®, Re-treatment of Relapsed Patients With Paget's Disease of Bone Who Participated in the CZOL446K2304 and CZOL446K2305 Core Registration Studies
| Registry | NCT00740129 |
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| Status | Completed |
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| Phase | Phase 4 |
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| Study type | Interventional; na, single group, masking: none, treatment |
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| Enrollment | 6 (Actual) |
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| Sponsor | Novartis Pharmaceuticals (Industry) |
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| Conditions | Paget's Disease of the Bone |
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| Interventions | Zoledronic Acid (Drug) |
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| Dates | start 2008-10-21, primary completion 2011-03-14, completion 2011-03-14, first posted 2008-08-22, last updated 2021-05-26 |
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| Locations | 11 sites in Belgium, Canada, New Zealand, South Africa, Spain, United Kingdom |
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Related Papers Related Patents Related Grants Related Experts
All trials for Paget's Disease of the Bone All trials of Zoledronic Acid
-Summary
The purpose of this study was to demonstrate that participants with Paget's disease of the bone who had responded to zoledronic acid treatment as participants in the core registration studies CZOL446K2304 and CZOL446K2305 and later experienced a relapse can be successfully treated with a 5 milligram (mg) infusion of zoledronic acid.
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+Detailed description
+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| Zoledronic Acid 5 mg | Experimental | Drug: Zoledronic Acid | Participants received single re-treatment dose of zoledronic acid 5 mg intravenous (IV) infusion. |
- Zoledronic Acid (Drug), also known as Reclast®/Aclasta®: Zoledronic acid 5 mg intravenous infusion once
+Outcome measures
Primary outcomes
- Percentage of Participants With Serum Alkaline Phosphatase Within the Normal Range at Month 6 Last Observation Carried Forward (LOCF) [Month 6]: Normalization of serum alkaline phosphatase (SAP) occurred if the SAP measurement fell within the normal ranges. The lower and upper limits of normal ranges were 31 and 110 Units/Liter (U/L) for participants with age ≤ 58 years old and 35 and 115 U/L for participants with age > 58 years old, respectively. Last observation carried forward (LOCF) was defined as the last post-baseline SAP value prior to month 6 for a participant who did not have an SAP value at month 6.
Secondary outcomes
- Percentage Change From Baseline in Serum Alkaline Phosphatase (SAP) Levels [Baseline, Months 3 and 6]: The percentage change in SAP at Months 3 and 6 relative to baseline were measured.
- Percentage of Participants With SAP Within the Normal Range [Months 3 and 6]: Normalization of SAP occurred if the SAP measurement fell within the normal ranges. The lower and upper limits of normal ranges were 31 and 110 Units/Liter (U/L) for participants with age ≤ 58 years old and 35 and 115 U/L for participants with age > 58 years old, respectively.
- Number of Participants With At Least One or More Treatment-Emergent Adverse Events (TEAEs) [6 months]: Adverse event was the appearance or worsening of any undesirable sign, symptom, or medical condition that occurred after starting the study drug even if the event was not considered to be related to study drug. TEAEs were defined as AEs that were absent prior to, but occurred after the i.v. infusion of study drug. TEAEs also included those that were present prior to the i.v. study drug infusion (i.e., as part of the extended observation period) but occurred at an increased severity after the i.v. infusion of study drug.
Other outcomes
- Collect Information Pertaining to Relapse Diagnosis to Define Retreatment Guidelines for Paget's Disease [6 months]
+Eligibility
Sex: All
Inclusion Criteria:
* Written Informed Consent
* Participants with Paget's disease randomized to the zoledronic acid arm from the CZOL446K2304 and CZOL446K2305 core studies and who were responders by 6 months
* Confirmed relapse of Paget's disease of bone (i.e., serum alkaline phosphatase (SAP) above upper limit of normal (ULN), bone scan, worsening clinical symptoms)
Exclusion Criteria:
* A participant previously treated with zoledronic acid who relapsed and was retreated with anti-resorptive bisphosphonate or calcitonin therapy within the last 12 months
* Bisphosphonate Hypersensitivity
* Participants with suspected/proven metastases at re-treatment
* Calculated creatinine clearance <35 milliliter/minute (mL/min) at screening
* Serum calcium level <2.07 millimole/liter (mmol/L) at screening
* Active primary hyperparathyroidism, hyperparathyroidism, hypoparathyroidism or hypothyroidism
Other protocol-defined inclusion/exclusion criteria may apply.
+Posted results
Participant flow
| Milestone | Zoledronic Acid 5 mg |
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| Started | 6 |
| Completed | 6 |
| Not completed | 0 |
Outcome results
- Percentage of Participants With Serum Alkaline Phosphatase Within the Normal Range at Month 6 Last Observation Carried Forward (LOCF) (Primary), Number, Percentage of Participants: Zoledronic Acid 5 mg 83.3 (35.9 to 99.6)
- Percentage Change From Baseline in Serum Alkaline Phosphatase (SAP) Levels (Secondary), Mean, percentage change: Zoledronic Acid 5 mg -53.12 +/- 7.607
- Percentage of Participants With SAP Within the Normal Range (Secondary), Number, percentage of participants: Zoledronic Acid 5 mg 100.0 (54.1 to 100.0)
- Number of Participants With At Least One or More Treatment-Emergent Adverse Events (TEAEs) (Secondary), Count of participants, Participants: Zoledronic Acid 5 mg 1
- Collect Information Pertaining to Relapse Diagnosis to Define Retreatment Guidelines for Paget's Disease (Other pre specified)
Adverse events
Time frame: 6 months
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|
| Zoledronic Acid 5 mg | 0/6 (0.0%) | 0/6 (0.0%) | 1/6 (16.7%) |
Other adverse events by term
| Term | Organ system | Zoledronic Acid 5 mg |
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| Influenza | Infections and infestations | 1/6 |
+Locations (11)
| Facility | City | Country | Status |
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| Novartis Investigative site | Brussels | Belgium | |
| Novartis Investigative site | Montreal | Canada | |
| Novartis Investigative site | Québec | Canada | |
| Novartis Investigative site | Auckland | New Zealand | |
| Novartis Investigative site | Cape Town | South Africa | |
| Novartis Investigative site | Barcelona | Spain | |
| Novartis Investigative site | Madrid | Spain | |
| Novartis Investigative site | Salamanca | Spain | |
| Novartis Investigative site | Valencia | Spain | |
| Novartis Investigative site | Nottingham | United Kingdom | |
| Novartis Investigative site | Oxford | United Kingdom | |
+Publications
- Results publication: Reid IR, Brown JP, Levitt N, Roman Ivorra JA, Bachiller-Corral J, Ross IL, Su G, Antunez-Flores O, Aftring RP. Re-treatment of relapsed Paget's disease of bone with zoledronic acid: results from an open-label study. Bonekey Rep. 2013 Nov 6;2:442. doi: 10.1038/bonekey.2013.176. eCollection 2013. PMID 24422139
+Funding