Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Parathyroid Hormone Levels in Children Aged 10-16 With Chronic Kidney Disease (CKD)

The study consists of two parts. Part 1 is an open-label single-dose, non-fasting, multicenter study to evaluate the pharmacokinetics (PK) of paricalcitol capsules in 12 children ages 10 to 16 years with CKD Stages 3 and 4. Part 2 of this study will be conducted as a 12 week randomized double-blind, placebo-controlled study, followed by 12 weeks open-label treatment. Participants active or enrolled under amendment 5 will enter a follow-up period and have study visits every 4 weeks until the final participant reaches Week 24.

Inclusion criteria

• Subject has chronic kidney disease Stage 3 or 4 as determined by estimated glomerular filtration rate (15 to 59 mL/min/1.73 m²) at Screening.
• Subject is not expected to begin dialysis for at least 6 months (in the opinion of the investigator).
• For entry into the Washout Period (for subjects who are currently on a vitamin D receptor activator [VDRA] and need to complete a 2 to 4 week washout), the subject must satisfy the following criteria based on the Screening laboratory values:

• estimated glomerular filtration rate between 15 to 59 mL/min/1.73 m².
• iPTH measurement that is greater than or equal to 60 pg/mL (Stage 3 subjects) or greater than or equal to 90 pg/mL (Stage 4 subjects).
• An adjusted serum calcium value greater than or equal to 8.2 mg/dL (2.05 mmol/L) to less than or equal to 10.5 mg/dL (2.63 mmol/L).
• A serum phosphorus value greater than or equal to 2.0 mg/dL (0.65 mmol/L but less than or equal to 6.0 mg/dL (1.94 mmol/L).
• For entry into the Treatment Phase (vitamin D receptor activator naïve subjects and those that have completed a 4 week washout), the subject must have:

• iPTH measurement that is greater than or equal to 75 pg/mL (Stage 3 subjects) or greater than or equal to 110 pg/mL (Stage 4 subjects).
• An adjusted serum calcium value greater than or equal to 8.4 mg/dL (2.10 mmol/L) but less than or equal to 10.2 mg/dL (2.55 mmol/L).
• A serum phosphorus value greater than or equal to 2.5 mg/dL (0.81 mmol/L) but less than or equal to 5.8 mg/dL (1.87 mmol/L).
• Must have 25-hydroxyvitamin D levels ≥ 30 ng/mL prior to washout, if not VDRA naïve, or treatment in Part II of the study.

Exclusion criteria

• All subjects that have had a small bowel transplant will be excluded from the study.
• Subject has had acute kidney failure within 12 weeks of the Screening Phase (defined as an acute rise in serum creatinine).
• Subject has had symptomatic or significant hypocalcemia requiring active vitamin D therapy (for example, calcitriol, paricalcitol, doxercalciferol or alfacalcidol) within 6 months prior to the Screening Phase.
• Subject has a history of active kidney stones (6 months prior to screening).
• Subject has chronic gastrointestinal disease, which in the investigator's opinion may cause significant gastrointestinal malabsorption.
• Subject is taking maintenance calcitonin, bisphosphonates, cinacalcet, glucocorticoids in an equivalent dose of greater than 5 mg prednisone daily, or other drugs known to affect calcium or bone metabolism within 4 weeks prior to treatment.