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®

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00668200
• Collaborator: (none)
• Enrollment: 81
• Locations: 9
• Arm: 1
• Duration (Months): 54
• Patients Per Site: 9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Paget's Disease of the Bone; Hypocalcemia	Drug: Reclast (ZOL446, zoledronic acid); Dietary Supplement: Calcium; Dietary Supplement: Vitamin D	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Post US Approval Voluntary Registry Study to Determine Incidence of Hypocalcemia Post Reclast® Treatment in Patients With Paget's Disease After Institution of Educational Strategies to Improve Adherence to Calcium and Vitamin D Supplementation
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Other: 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.

Drug: Reclast (ZOL446, zoledronic acid); 5 mg i.v. annually ("real-life, physician prescribed"); Other Names: Reclast, ZOL446 ; Dietary Supplement: Calcium; 1500 mg elemental calcium daily in divided doses (the divided doses were 2-3 times per day depending on the formulation); Dietary Supplement: Vitamin D; 800 IU vitamin D daily, particularly in the immediate 2 weeks following zoledronic acid administration

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Written informed consent

• As per currently approved Reclast® Package Insert:

Exclusion Criteria:

• As per currently approved Reclast® Package Insert:

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Phoenix	Arizona	United States	85012
2	Novartis Investigative Site	Tucson	Arizona	United States	85723-0001
3	Novartis Investigative Site	Gainesville	Georgia	United States	30501
4	Novartis Investigative Site	Detroit	Michigan	United States	48236
5	Novartis Investigative Site	Syracuse	New York	United States	13210-2306
6	Novartis Investigative Site	Providence	Rhode Island	United States	02908
7	Novartis Investigative Site	Dallas	Texas	United States	75216
8	Novartis Investigative Site	Waco	Texas	United States	76708
9	Novartis Investigative Site	Madison	Wisconsin	United States	53705-3611

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00668200
• Other Study ID Numbers: CZOL446K2401
• First Posted: Apr 29, 2008
• Last Update Posted: Mar 6, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Paget's; hypocalcemia; zoledronic acid; serum calcium
• Additional relevant MeSH terms: Bone Diseases; Osteitis Deformans; Hypocalcemia; Vitamin D; Zoledronic Acid; Calcium

Study Results

Participant Flow

Arm/Group Title	Zoledronic Acid
Arm/Group Description	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.
Period Title: Overall Study
STARTED	80
Safety Population	81
Intent to Treat (ITT)	80
COMPLETED	77
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Zoledronic Acid
Arm/Group Description	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 Participants	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.5 (12.98)
Sex: Female, Male (Count of Participants)
Female	29 36.3%
Male	51 63.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Serum Calcium <2.07 mmol/L at 9-11 Days After Receiving Zoledronic Acid.
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Zoledronic Acid
Arm/Group Description	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.
Measure Participants	75
Visit 2	1.3
Visit 3	0.0

2. Secondary Outcome

Title	Change From Baseline in Serum Calcium (mmol/L) - Safety Population
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Zoledronic Acid
Arm/Group Description	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.
Measure Participants	81
Visit 2 n=76	-0.024 (0.189)
Visit 3 n=2	0.04 (0.014)

3. Secondary Outcome

Title	Percentage of Newly Occurring Post-baseline Hypocalcemia Symptoms Based on Hypocalcemia Questionnaire at End of Study Visit 2 or Visit 3 (Safety Population)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Zoledronic Acid
Arm/Group Description	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.
Measure Participants	81
Tingling around your mouth n=76	1.3
Tingling in fingers n=66	3
Cramps in hands n=62	3.2
Cramps in leg or feet n=50	0
Involuntary movements of hands n=73	2.7
Involuntary movements of feet n=70	1.4
Involuntary movements of facial muscles n=71	0
Generalized (epileptic) seizures n=76	0

Adverse Events

Arm/Group Title	Zoledronic Acid
Arm/Group Description	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.
All Cause Mortality
	Zoledronic Acid
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Zoledronic Acid
	Affected / at Risk (%)	# Events
Total	1/81 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm	1/81 (1.2%)
Other (Not Including Serious) Adverse Events
	Zoledronic Acid
	Affected / at Risk (%)	# Events
Total	24/81 (29.6%)
General disorders
Acute phase reaction	6/81 (7.4%)
Chills	10/81 (12.3%)
Malaise	6/81 (7.4%)
Pain	9/81 (11.1%)
Pyrexia	5/81 (6.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.