Trial Outcomes & Findings for Impact on Reducing the Incidence of Low Serum Calcium by Providing Educational Materials on the Need to Take Daily Supplemental Calcium and Vitamin D to Patients With Paget's Disease Treated With Reclast® (NCT NCT00668200)

NCT ID: NCT00668200

Last Updated: 2015-03-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

81 participants

Primary outcome timeframe

at Visit 2 (days 9 - 11 post-infusion), visit 3 (day 30)

Results posted on

2015-03-06

Participant Flow

Participant milestones

Participant milestones
Measure
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.
Overall Study
STARTED
80
Overall Study
Safety Population
81
Overall Study
Intent to Treat (ITT)
80
Overall Study
COMPLETED
77
Overall Study
NOT COMPLETED
3

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
Overall Study
Withdrawal by Subject
2
Overall Study
Lost to Follow-up
1

Baseline Characteristics

Impact on Reducing the Incidence of Low Serum Calcium by Providing Educational Materials on the Need to Take Daily Supplemental Calcium and Vitamin D to Patients With Paget's Disease Treated With Reclast®

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Zoledronic Acid
n=80 Participants
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.
Age, Continuous
71.5 years
STANDARD_DEVIATION 12.98 • n=5 Participants
Sex: Female, Male
Female
29 Participants
n=5 Participants
Sex: Female, Male
Male
51 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Zoledronic Acid
n=75 Participants
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.
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
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 outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Zoledronic Acid
n=81 Participants
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.
Change From Baseline in Serum Calcium (mmol/L) - Safety Population
Visit 2 n=76
-0.024 mmol/L
Standard Deviation 0.189
Change From Baseline in Serum Calcium (mmol/L) - Safety Population
Visit 3 n=2
0.04 mmol/L
Standard Deviation 0.014

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Zoledronic Acid
n=81 Participants
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.
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
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
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
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
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
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
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
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

Adverse Events

Zoledronic Acid

Serious events: 1 serious events
Other events: 24 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Zoledronic Acid
n=81 participants at risk
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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm
1.2%
1/81

Other adverse events

Other adverse events
Measure
Zoledronic Acid
n=81 participants at risk
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.
General disorders
Acute phase reaction
7.4%
6/81
General disorders
Chills
12.3%
10/81
General disorders
Malaise
7.4%
6/81
General disorders
Pain
11.1%
9/81
General disorders
Pyrexia
6.2%
5/81

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 8627788300

Results disclosure agreements

  • Principal investigator is a sponsor employee Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial.
  • Publication restrictions are in place

Restriction type: OTHER