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”

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.

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.

Intervention(s) in this Clinical Trial

• 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.
• Drug: 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.

Arms, Groups and Cohorts in this Clinical Trial

• Other: Calcitriol challenge followed by paricalcitol
  • 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.

Primary Measures

• Proportion of Participants With a 50% Reduction in Parathyroid Hormone (PTH) Levels Relative to Visit 4 Values
  • Time Frame: Up to Week 24
    Safety Issue?: No

Secondary Measures

• Changes in Bone Remodeling Markers Over Time
  • Time Frame: Every 3 months
    Safety Issue?: No
• Number of Participants With Adverse Events
  • Time Frame: Up to 1 year
    Safety Issue?: Yes

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Abbott Industry

Overall Clinical Trial Officials and Contacts

Lino Rodrigues, MD Study Director Abbott  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00664430

Study ID Number: W10-131

ClinicalTrials.gov Identifier: NCT00664430

Health Authority: Brazil: Ethics Committee