Efficacy and Safety of Paricalcitol on the Treatment of Secondary Hyperparathyroidism in Calcitriol Resistant Dialysis Subjects
Primary Purpose
Secondary Hyperparathyroidism, Dialysis
Status
Terminated
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Calcitriol
Paricalcitol
Sponsored by
About this trial
This is an interventional treatment trial for Secondary Hyperparathyroidism focused on measuring Dialysis, Calcitriol Resistant, Secondary Hyperparathyroidism
Eligibility Criteria
Inclusion Criteria:
- Male and female participants > 18 years of age, with chronic kidney disease (CKD) stage V;
- Participants with diagnosis of calcitriol resistance defined as: Episodes of hypercalcemia and/or hyperphosphatemia (defined as an episode of calcium or phosphorus above Upper Limit of Normal or documented by medical history stating that the treatment with calcitriol was discontinued due to hypercalcemia and/or hyperphosphatemia) that precludes treatment continuation and/or persistent PTH above 600pg/mL during the calcitriol therapy;
- PTH value at screening visit between 600 pg/mL and 2,000 pg/mL;
- Stable clinical conditions;
- Participant has voluntarily consented to participate in the study, by signing and dating an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and all his questions about the study have been elucidated. The informed consent must be signed before any study-specific procedures are performed.
Exclusion Criteria:
- Previous parathyroidectomy;
- Presence of hypercalcemia (corrected Ca > 10.5 mg/dL) and/or hyperphosphatemia (P > 6.0 mg/dL) and/or Ca x P product > 60, at screening visit (corrected Ca calculated by: [4 - participant's serum albumin (g/dL)] x 0.8 + participant's serum Ca value);
- Severe and/or unstable clinical conditions, e.g., congestive heart failure, advanced cancer, advanced HIV disease, severe endocrinopathies, uncompensated diabetes mellitus, life-threatening cardiac arrhythmias, etc;
- Abnormal liver tests (> 1.5 times above upper limit of normal);
- Pregnant or breast-feeding women;
- Evidence of vitamin D toxicity;
- Known hypersensitivity to any study drug components.
Sites / Locations
- Site Reference ID/Investigator# 7118
- Site Reference ID/Investigator# 7114
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Calcitriol challenge followed by paricalcitol
Arm Description
Participants began a controlled calcitriol therapy period (calcitriol challenge) to confirm calcitriol resistance. After this period, those who failed to reduce PTH (according to parameters in protocol) initiated paricalcitol therapy.
Outcomes
Primary Outcome Measures
Proportion of Participants With a 50% Reduction in Parathyroid Hormone (PTH) Levels Relative to Visit 4 Values
This outcome was measured at Visit 15, which could occur at different timepoints from study start, depending on the duration of each study period for each participant, relative to values on Visit 4. For participants who did not perform visit 4, the reduction of the PTH levels were to be assessed relative to visit 5 values.
Secondary Outcome Measures
Changes in Bone Remodeling Markers Over Time
Deoxypyridinoline and bone-specific alkaline phosphatase levels were to be measured every 3 months and changes over time analyzed using descriptive statistics.
Number of Participants With Adverse Events
The occurrence of adverse events was considered a secondary endpoint in this study. For details on adverse events that occurred prior to study termination, refer to the safety section below.
Full Information
NCT ID
NCT00664430
First Posted
April 21, 2008
Last Updated
January 18, 2012
Sponsor
Abbott
Collaborators
Statistika Consultoria Ltda
1. Study Identification
Unique Protocol Identification Number
NCT00664430
Brief Title
Efficacy and Safety of Paricalcitol on the Treatment of Secondary Hyperparathyroidism in Calcitriol Resistant Dialysis Subjects
Official Title
Efficacy and Safety of Paricalcitol on the Treatment of Secondary Hyperparathyroidism in Calcitriol Resistant Dialysis Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
January 2012
Overall Recruitment Status
Terminated
Why Stopped
Low enrollment rate
Study Start Date
January 2009 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
June 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abbott
Collaborators
Statistika Consultoria Ltda
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this study is to evaluate the efficacy and safety of paricalcitol in participants with moderate to severe secondary hyperparathyroidism (SHPT) undergoing hemodialysis who are resistant to treatment with calcitriol.
Detailed Description
This is a multi-center, prospective, open label, one arm, phase IV study designed to demonstrate paricalcitol efficacy and safety in the treatment of moderate to severe secondary hyperparathyroidism in calcitriol resistant participants on dialysis.
Following screening, participants began an 8-week controlled calcitriol therapy period. Participants whose parathyroid hormone (PTH) levels decreased were to be discontinued from the study. Those whose PTH levels did not decrease began paricalcitol therapy using a dose calculated by 0.04 to 0.1 microgram per kilogram (mcg/kg). Paricalcitol was administered intravenously at anytime during the subjects' dialysis. The paricalcitol dose was to be titrated every 2 weeks until iPTH was reduced or up to 4 months, after which it was to be adjusted monthly for 1 year based on serum PTH, calcium, phosphorus, and albumin measurements.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Hyperparathyroidism, Dialysis
Keywords
Dialysis, Calcitriol Resistant, Secondary Hyperparathyroidism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Calcitriol challenge followed by paricalcitol
Arm Type
Other
Arm Description
Participants began a controlled calcitriol therapy period (calcitriol challenge) to confirm calcitriol resistance. After this period, those who failed to reduce PTH (according to parameters in protocol) initiated paricalcitol therapy.
Intervention Type
Drug
Intervention Name(s)
Calcitriol
Other Intervention Name(s)
Calcijex
Intervention Description
Initial doses determined according to the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guideline (Am J Kidney Dis 2003;42(4)Suppl 3:S1-S201). During therapy, calcitriol dose may be modified by 0.5 - 1 mcg at 2- to 4-week intervals.
Intervention Type
Drug
Intervention Name(s)
Paricalcitol
Other Intervention Name(s)
ABT-358, Zemplar, Paracalcitol
Intervention Description
Dose calculated by 0.04 to 0.1 microgram per kilogram (mcg/kg). Paricalcitol will be administered intravenously after the participants' dialysis. The paricalcitol dose will be titrated every 2 weeks until iPTH presents a reduction or up to 4 months, after which it will be adjusted monthly based on serum PTH, calcium, phosphorus and albumin measurements. Dosing may be modified by 2-4 mcg increments at 2- to 4-week intervals.
Primary Outcome Measure Information:
Title
Proportion of Participants With a 50% Reduction in Parathyroid Hormone (PTH) Levels Relative to Visit 4 Values
Description
This outcome was measured at Visit 15, which could occur at different timepoints from study start, depending on the duration of each study period for each participant, relative to values on Visit 4. For participants who did not perform visit 4, the reduction of the PTH levels were to be assessed relative to visit 5 values.
Time Frame
Up to Week 24
Secondary Outcome Measure Information:
Title
Changes in Bone Remodeling Markers Over Time
Description
Deoxypyridinoline and bone-specific alkaline phosphatase levels were to be measured every 3 months and changes over time analyzed using descriptive statistics.
Time Frame
Every 3 months
Title
Number of Participants With Adverse Events
Description
The occurrence of adverse events was considered a secondary endpoint in this study. For details on adverse events that occurred prior to study termination, refer to the safety section below.
Time Frame
Up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female participants > 18 years of age, with chronic kidney disease (CKD) stage V;
Participants with diagnosis of calcitriol resistance defined as: Episodes of hypercalcemia and/or hyperphosphatemia (defined as an episode of calcium or phosphorus above Upper Limit of Normal or documented by medical history stating that the treatment with calcitriol was discontinued due to hypercalcemia and/or hyperphosphatemia) that precludes treatment continuation and/or persistent PTH above 600pg/mL during the calcitriol therapy;
PTH value at screening visit between 600 pg/mL and 2,000 pg/mL;
Stable clinical conditions;
Participant has voluntarily consented to participate in the study, by signing and dating an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and all his questions about the study have been elucidated. The informed consent must be signed before any study-specific procedures are performed.
Exclusion Criteria:
Previous parathyroidectomy;
Presence of hypercalcemia (corrected Ca > 10.5 mg/dL) and/or hyperphosphatemia (P > 6.0 mg/dL) and/or Ca x P product > 60, at screening visit (corrected Ca calculated by: [4 - participant's serum albumin (g/dL)] x 0.8 + participant's serum Ca value);
Severe and/or unstable clinical conditions, e.g., congestive heart failure, advanced cancer, advanced HIV disease, severe endocrinopathies, uncompensated diabetes mellitus, life-threatening cardiac arrhythmias, etc;
Abnormal liver tests (> 1.5 times above upper limit of normal);
Pregnant or breast-feeding women;
Evidence of vitamin D toxicity;
Known hypersensitivity to any study drug components.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lino Rodrigues, MD
Organizational Affiliation
Abbott
Official's Role
Study Director
Facility Information:
Facility Name
Site Reference ID/Investigator# 7118
City
Sao Paulo
ZIP/Postal Code
04039-001
Country
Brazil
Facility Name
Site Reference ID/Investigator# 7114
City
Sao Paulo
ZIP/Postal Code
05403-000
Country
Brazil
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Paricalcitol on the Treatment of Secondary Hyperparathyroidism in Calcitriol Resistant Dialysis Subjects
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