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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Secondary Hyperparathyroidism, Dialysis

Intervention / Treatment
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* Drug: Calcitriol
* Drug: Paricalcitol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Calcitriol challenge followed by paricalcitol<br>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. | Drug: Calcitriol<br>* 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.<br>* Other names: Calcijex;Drug: Paricalcitol<br>* 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.<br>* Other names: Paracalcitol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dialysis, Calcitriol Resistant, Secondary Hyperparathyroidism