Paget's Disease of the Bone
Conditions
Keywords
Paget's Disease, Zoledronic acid, Reclast®/Aclasta®, Infusion, Re-treatment, Re-lapse
Brief 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.
Detailed description
Uncontrolled study
Interventions
DRUGZoledronic Acid
Zoledronic acid 5 mg intravenous infusion once
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Collect Information Pertaining to Relapse Diagnosis to Define Retreatment Guidelines for Paget's Disease | 6 months |
Countries
Belgium, Canada, New Zealand, South Africa, Spain, United Kingdom
Participant flow
Recruitment details
A total of 6 participants from core studies CZOL44K2304 and CZOL44K2305 who met the definition of responders at the end of study visit but later relapsed during the extension of observation period took part in the study at 5 investigative sites in Canada, Spain, New Zealand and, South Africa from 21 October 2008 to 14 March 2011.
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid 5 mg Participants received single re-treatment dose of zoledronic acid 5 mg IV infusion. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Zoledronic Acid 5 mg |
|---|---|
| Age, Continuous | 75.2 years STANDARD_DEVIATION 6.08 |
| Baseline Serum Alkaline Phosphatase | 200.3 Units/Liter (U/L) STANDARD_DEVIATION 59.62 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Percentage of Participants With Serum Alkaline Phosphatase Within the Normal Range at Month 6 Last Observation Carried Forward (LOCF)
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.
Time frame: Month 6
Population: Modified Intent-to-Treat (MITT) Population included all enrolled participants who were previously randomized to zoledronic acid in the core studies (CZOL44K2304 and CZOL44K2305) and received the intravenous study drug and had baseline and at least one post-baseline assessment of the serum SAP in this retreatment study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoledronic Acid 5 mg | Percentage of Participants With Serum Alkaline Phosphatase Within the Normal Range at Month 6 Last Observation Carried Forward (LOCF) | 83.3 Percentage of Participants |
Secondary
Number of Participants With At Least One or More Treatment-Emergent Adverse Events (TEAEs)
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.
Time frame: 6 months
Population: Safety Population included all enrolled participants previously randomized to zoledronic acid in the core studies (CZOL44K2304 and CZOL44K2305) who received intravenous study drug in this retreatment study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoledronic Acid 5 mg | Number of Participants With At Least One or More Treatment-Emergent Adverse Events (TEAEs) | 1 Participants |
Secondary
Percentage Change From Baseline in Serum Alkaline Phosphatase (SAP) Levels
The percentage change in SAP at Months 3 and 6 relative to baseline were measured.
Time frame: Baseline, Months 3 and 6
Population: MITT Population included all enrolled participants who were previously randomized to zoledronic acid in the core studies (CZOL44K2304 and CZOL44K2305) and received the intravenous study drug and had baseline and at least one post-baseline assessment of the serum SAP in this retreatment study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zoledronic Acid 5 mg | Percentage Change From Baseline in Serum Alkaline Phosphatase (SAP) Levels | Percentage Change From Baseline in SAP Level at Month 3 | -53.12 percentage change | Standard Error 7.607 |
| Zoledronic Acid 5 mg | Percentage Change From Baseline in Serum Alkaline Phosphatase (SAP) Levels | Percentage Change From Baseline in SAP Level at Month 6 | -49.51 percentage change | Standard Error 10.09 |
Secondary
Percentage of Participants With SAP Within the Normal Range
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.
Time frame: Months 3 and 6
Population: MITT Population included all enrolled participants who were previously randomized to zoledronic acid in the core studies (CZOL44K2304and CZOL44K2305) and received the intravenous study drug and had baseline and at least one post-baseline assessment of the serum SAP in this retreatment study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zoledronic Acid 5 mg | Percentage of Participants With SAP Within the Normal Range | Month 3 | 100.0 percentage of participants |
| Zoledronic Acid 5 mg | Percentage of Participants With SAP Within the Normal Range | Month 6 | 83.3 percentage of participants |
Other Pre-specified
Collect Information Pertaining to Relapse Diagnosis to Define Retreatment Guidelines for Paget's Disease
Time frame: 6 months