A Study to Evaluate the Safety of Paricalcitol Capsules in Pediatric Subjects Ages 10 to 16 With Stage 5 Chronic Kidney Disease Receiving Peritoneal Dialysis or Hemodialysis

Study Overview
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Brief Summary
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The objective is to evaluate the safety of paricalcitol capsules in pediatric subjects, ages 10 to 16 years old, with Stage 5 chronic kidney disease (kidney failure) receiving peritoneal dialysis or hemodialysis and being treated for secondary hyperparathyroidism. Subjects will be in the dosing period of the study for 12 weeks in order to evaluate the incidence of hypercalcemia (high calcium levels in blood). Approximately 12 subjects will be enrolled and all 12 will receive paricalcitol capsules.

Official Title
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A Phase 3, Open-Label, Multicenter Study to Evaluate the Safety of Paricalcitol Capsules in Pediatric Subjects Ages 10 to 16 With Stage 5 Chronic Kidney Disease Receiving Peritoneal Dialysis or Hemodialysis

Conditions
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End-Stage Renal Disease, Secondary Hyperparathyroidism

Intervention / Treatment
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* Drug: paricalcitol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be receiving peritoneal dialysis or hemodialysis for at least 3 months prior to Screening Subject is currently being diagnosed and/or treated for secondary hyperparathyroidism For entry into the Dosing Period (for subjects that are naïve to Vitamin D Receptor [VDR] Activators or those who have completed a 2 to 12 week washout), the subject must meet the following laboratory criteria prior to enrollment: A corrected calcium value ≥ 8.2 and ≤ 10.4 mg/dL A phosphorus value ≤ 6.5 mg/dL An intact parathyroid hormone (iPTH) value > 300 pg/mL and less ≤ 2000 pg/mL Exclusion Criteria: Subject is expected or scheduled to receive a living donor kidney transplant within 3 months of Screening or is a kidney transplant patient requiring full immunosuppressant therapy Subject is expected to stop peritoneal dialysis or hemodialysis within 4 months of Screening (per investigator discretion) Subject has had a parathyroidectomy within 12 weeks prior to Screening Subject has had symptomatic or significant hypocalcemia requiring VDR Activator therapy (i.e., calcitriol, paricalcitol, or doxercalciferol) within 2 months prior to Screening Subject is taking maintenance calcitonin, bisphosphonates, glucocorticoids in an equivalent dose of greater than 5 mg prednisone daily, or other drugs known to affect calcium or bone metabolism within 4 to 8 weeks prior to Dosing Subject is receiving cinacalcet at the time of Screening

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 16 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paricalcitol<br>Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks. | Drug: paricalcitol<br>* Paricalcitol soft capsule. Starting dose of paricalcitol was determined by the intact parathyroid hormone (iPTH) value (iPTH/120) from prior to Day 1, rounded down to the nearest whole number, not to exceed 16 µg 3 times weekly, no more frequently than every other day. Decisions to hold, maintain, increase, or decrease a dose were based on the iPTH, phosphorus, and calcium results generated from the most recent visit and within target Kidney Dialysis Outcomes Quality Initiatives (KDOQI) levels.<br>* Other names: ABT-358, Zemplar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Hypercalcemia | The percentage of subjects with hypercalcemia, defined as at least 2 consecutive post-baseline corrected calcium values > 10.2 mg/dL (2.55 mmol/L). | Day 1 to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With 2 Consecutive Intact Parathyroid Hormone (iPTH)/120 Between 150 and 300 pg/mL |  | Baseline (last measurement collected prior to the first dose) to Week 12 | 
| Percentage of Subjects With 2 Consecutive iPTH Reductions of at Least 30% From Baseline |  | Baseline (last measurement collected prior to the first dose) to Week 12 | 
| Hemoglobin: Mean Change From Baseline to Final Visit |  | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Hematocrit: Mean Change From Baseline to Final Visit |  | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Red Blood Cells: Mean Change From Baseline to Final Visit |  | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| White Blood Cells (WBC) and Platelet Count: Mean Change From Baseline to Final Visit |  | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils: Mean Change From Baseline to Final Visit |  | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactic Dehydrogenase (LDH), and Bone-Specific Alkaline Phosphatase (BSAP): Mean Change From Baseline to Final Visit | n=subjects with evaluable Baseline and Post-baseline data for each parameter. | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Bilirubin, Blood Urea Nitrogen (BUN), Uric Acid, Magnesium, Glucose, Cholesterol, Triglycerides, High Sensitivity C-Reactive Protein (hsCRP), Inorganic Phosphate, Corrected Calcium, and Creatinine: Mean Change From Baseline to Final Visit | n=subjects with evaluable Baseline and Post-baseline data for each parameter. | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Alkaline Phosphatase: Mean Change From Baseline to Final Visit |  | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Sodium, Potassium, Chloride, Bicarbonate: Mean Change From Baseline to Final Visit |  | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Total Protein and Albumin: Mean Change From Baseline to Final Visit | n=subjects with evaluable Baseline and Post-baseline data for each parameter. | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Fibroblast Growth Factor-23 (FGF-23), 1,25-Hydroxy Vitamin D, 25-Hydroxy Vitamin D, and Intact Parathyroid Hormone (iPTH): Mean Change From Baseline to Final Visit | n=subjects with evaluable Baseline and Post-baseline data for each parameter. | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Osteocalcin: Mean Change From Baseline to Final Visit |  | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Number of Subjects With Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. For more details on adverse events please see the Adverse Event section. | From first dose of study drug until 30 days following last dose of study drug (up to 16 weeks). | 
| Number of Subjects With Potentially Clinically Significant Electrocardiogram (ECG) Findings | 12-lead ECGs were recorded after the subject had been in the supine position for at least 5 minutes. The number of subjects with potentially clinically significant ECG findings, as determined by the investigator, is presented. | Baseline (Day 1) to Final Visit (up to Week 12) | 
| Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Mean Change From Baseline to Final Visit | Blood pressure was measured after the subject had been sitting for at least 3 minutes. | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Heart Rate: Mean Change From Baseline to Final Visit | Heart rate was measured after the subject had been sitting for at least 3 minutes. | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Oral Body Temperature: Mean Change From Baseline to Final Visit |  | Baseline (last measurement collected prior to the first dose) to Final Visit (up to Week 12) | 
| Number of Subjects With Potentially Clinically Significant Physical Examination Findings |  | Baseline (Day 1) and Final Visit (up to Week 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Evaluate safety through the evaluation of the incidence of hypercalcemia in pediatric subjects