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

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

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.

Study Overview

• Status: Completed
• Conditions: End-Stage Renal Disease; Secondary Hyperparathyroidism
• Intervention / Treatment: Drug: paricalcitol

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Paricalcitol; Open-label paricalcitol (maximum dose of 16 µg), 3 times weekly (no more frequently than every other day) for 12 weeks.

Drug: paricalcitol; 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.; Other Names: ABT-358, Zemplar

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)

Publications and helpful links

General Publications

• Webb NJA, Lerner G, Warady BA, Dell KM, Greenbaum LA, Ariceta G, Hoppe B, Linde P, Lee HJ, Eldred A, Dufek MB. Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease. Pediatr Nephrol. 2017 Jul;32(7):1221-1232. doi: 10.1007/s00467-017-3579-6. Epub 2017 Mar 22.

Helpful Links

• Prescribing Information

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: June 24, 2011
• First Submitted That Met QC Criteria: June 24, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Actual): July 2, 2018
• Last Update Submitted That Met QC Criteria: June 1, 2018
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Evaluate safety through the evaluation of the incidence of hypercalcemia in pediatric subjects
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Kidney Failure, Chronic; Hyperparathyroidism, Secondary
• Other Study ID Numbers: M11-612; 2013-002610-13 (EudraCT Number)