Hypocalcemia, Paget's Disease of the Bone
Conditions
Keywords
Paget's, hypocalcemia, zoledronic acid, serum calcium
Brief summary
This study will evaluate the impact of investigator and patient education and educational materials to foster calcium and vitamin D supplementation to mitigate the potential for hypocalcemia post Reclast® administration in patients with Paget's disease of bone.
Interventions
DRUGReclast (ZOL446, zoledronic acid)
5 mg i.v. annually (real-life, physician prescribed)
DIETARY_SUPPLEMENTCalcium
1500 mg elemental calcium daily in divided doses (the divided doses were 2-3 times per day depending on the formulation)
DIETARY_SUPPLEMENTVitamin D
800 IU vitamin D daily, particularly in the immediate 2 weeks following zoledronic acid administration
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Written informed consent * As per currently approved Reclast® Package Insert:
Exclusion criteria
\- As per currently approved Reclast® Package Insert:
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Serum Calcium <2.07 mmol/L at 9-11 Days After Receiving Zoledronic Acid. | at Visit 2 (days 9 - 11 post-infusion), visit 3 (day 30) | To be included in the analysis, patients were required to have a baseline serum calcium of at least 2.07 mmol/L and at least one serum calcium measurement 9-11 days post-infusion of zoledronic acid. In case of multiple assessments, for baseline visit the last measurement prior to the first dose was used in the analysis, and for Visits 2 and 3, the lowest serum calcium in the visit window was used. hypocalcemia was defined as treatment-emergent serum calcium \<2.07 mmol/L at 9-11 days after the study drug infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum Calcium (mmol/L) - Safety Population | Baseline, Visit 2 (days 9 - 11 post-infusion), visit 3 (day 30) | Change from baseline = endpoint - baseline, at each time point, only participants with a value at baseline and that time point are included in the change from baseline column. In case of multiple assessments, for baseline visit the last measurement prior to the first dose was used in the analysis, and for Visits 2 and 3, the lowest serum calcium in the visit window was used. |
| Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population) | End of study: Visit 2 (days 9 - 11 post-infusion) or visit 3 (day 30) | The end of study is not a separate time point. It is the last post-baseline, for majority the end of study was visit 2. There were 2 patients who had the end of study at Visit 3. If calcium at visit 2 was abnormal it was measured again at visit 3. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid 5 mg of Reclast (ZOL446, zoledronic acid) injection in 100 mL ready to infuse solution administered intravenously via a vented line. The infusion time was to be not less than 15 minutes given over a constant infusion rate. | 80 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Zoledronic Acid |
|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 12.98 |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 81 |
| serious Total, serious adverse events | 1 / 81 |
Outcome results
Primary
Percentage of Patients With Serum Calcium <2.07 mmol/L at 9-11 Days After Receiving Zoledronic Acid.
To be included in the analysis, patients were required to have a baseline serum calcium of at least 2.07 mmol/L and at least one serum calcium measurement 9-11 days post-infusion of zoledronic acid. In case of multiple assessments, for baseline visit the last measurement prior to the first dose was used in the analysis, and for Visits 2 and 3, the lowest serum calcium in the visit window was used. hypocalcemia was defined as treatment-emergent serum calcium \<2.07 mmol/L at 9-11 days after the study drug infusion.
Time frame: at Visit 2 (days 9 - 11 post-infusion), visit 3 (day 30)
Population: Safety population which includes 81 patients was used. 75 of the 81 patients in the safety population met the criteria. 6 patients did not meet criteria and were excluded from the analysis: 1 patient had a low serum calcium at baseline, and the other 5 patients were missing serum calcium values either at baseline or post-baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zoledronic Acid | Percentage of Patients With Serum Calcium <2.07 mmol/L at 9-11 Days After Receiving Zoledronic Acid. | Visit 2 | 1.3 percentage of patients |
| Zoledronic Acid | Percentage of Patients With Serum Calcium <2.07 mmol/L at 9-11 Days After Receiving Zoledronic Acid. | Visit 3 | 0.0 percentage of patients |
Secondary
Change From Baseline in Serum Calcium (mmol/L) - Safety Population
Change from baseline = endpoint - baseline, at each time point, only participants with a value at baseline and that time point are included in the change from baseline column. In case of multiple assessments, for baseline visit the last measurement prior to the first dose was used in the analysis, and for Visits 2 and 3, the lowest serum calcium in the visit window was used.
Time frame: Baseline, Visit 2 (days 9 - 11 post-infusion), visit 3 (day 30)
Population: This Outcome Measure uses Safety population which includes 81 patients. During monitoring it was discovered that one patient signed the consent form from another Paget's study; therefore, this patient was excluded from the ITT population but included in the safety. The ITT population was used for participant flow and baseline characteristics.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zoledronic Acid | Change From Baseline in Serum Calcium (mmol/L) - Safety Population | Visit 2 n=76 | -0.024 mmol/L | Standard Deviation 0.189 |
| Zoledronic Acid | Change From Baseline in Serum Calcium (mmol/L) - Safety Population | Visit 3 n=2 | 0.04 mmol/L | Standard Deviation 0.014 |
Secondary
Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population)
The end of study is not a separate time point. It is the last post-baseline, for majority the end of study was visit 2. There were 2 patients who had the end of study at Visit 3. If calcium at visit 2 was abnormal it was measured again at visit 3.
Time frame: End of study: Visit 2 (days 9 - 11 post-infusion) or visit 3 (day 30)
Population: This Outcome Measure uses Safety population which includes 81 patients. During monitoring it was discovered that one patient signed the consent form from another Paget's study; therefore, this patient was excluded from the ITT population but included in the safety. The ITT population was used for participant flow and baseline characteristics.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zoledronic Acid | Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population) | Involuntary movements of feet n=70 | 1.4 percentage of patients |
| Zoledronic Acid | Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population) | Tingling around your mouth n=76 | 1.3 percentage of patients |
| Zoledronic Acid | Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population) | Tingling in fingers n=66 | 3 percentage of patients |
| Zoledronic Acid | Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population) | Cramps in hands n=62 | 3.2 percentage of patients |
| Zoledronic Acid | Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population) | Cramps in leg or feet n=50 | 0 percentage of patients |
| Zoledronic Acid | Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population) | Involuntary movements of hands n=73 | 2.7 percentage of patients |
| Zoledronic Acid | Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population) | Involuntary movements of facial muscles n=71 | 0 percentage of patients |
| Zoledronic Acid | Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population) | Generalized (epileptic) seizures n=76 | 0 percentage of patients |