Efficacy and Safety of Paricalcitol on the Treatment of Secondary Hyperparathyroidism in Calcitriol Resistant Dialysis Subjects

Secondary Hyperparathyroidism Clinical Trial

Official title:

Efficacy and Safety of Paricalcitol on the Treatment of Secondary Hyperparathyroidism in Calcitriol Resistant Dialysis Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00664430
• Other study ID #: W10-131
• Status: Terminated
• Phase: Phase 4
• First received: April 21, 2008
• Last updated: January 18, 2012
• Start date: January 2009
• Est. completion date: June 2009

Study information

• Verified date: January 2012
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics CommitteeBrazil: National Health Surveillance Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dialysis
• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Neoplasm Metastasis
• Secondary Hyperparathyroidism

Intervention

Drug:
• Calcitriol
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.
• Paricalcitol
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.

Locations

Country	Name	City	State
Brazil	Site Reference ID/Investigator# 7114	Sao Paulo
Brazil	Site Reference ID/Investigator# 7118	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
Abbott	Statistika Consultoria Ltda

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to Week 24	No
Secondary	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.	Every 3 months	No
Secondary	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.	Up to 1 year	Yes