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

• The proportion of subjects who achieve a final intact parathyroid hormone values within Kidney Disease Outcomes Quality Initiative intact parathyroid hormone target ranges will be evaluated within each Chronic Kidney Disease stage. [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
• The proportion of subjects who achieve a final value within the applicable Kidney Disease Outcomes Quality Initiative target ranges for calcium. [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
• The proportion of subjects who achieve a final value within the applicable Kidney Disease Outcomes Quality Initiative target ranges for phosphorus. [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
• The mean percent change in intact parathyroid hormone from baseline to each post baseline visit (Weeks 2, 4, 8 and 12). [ Time Frame: 2 Weeks ] [ Designated as safety issue: No ]
• The mean percent change in intact parathyroid hormone from baseline to each post baseline visit (Weeks 2, 4, 8 and 12). [ Time Frame: 4 Weeks ] [ Designated as safety issue: No ]
• The mean percent change in intact parathyroid hormone from baseline to each post baseline visit (Weeks 2, 4, 8 and 12). [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
• The mean percent change in intact parathyroid hormone from baseline to each post baseline visit (Weeks 2, 4, 8 and 12). [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
• The mean change in First Morning Void Urine Albumin/Creatinine Ratio from baseline to each post baseline visit (Weeks 4, 8 and 12). [ Time Frame: 4 Weeks ] [ Designated as safety issue: No ]
• The mean change in First Morning Void Urine Albumin/Creatinine Ratio from baseline to each post baseline visit (Weeks 4, 8 and 12). [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
• The mean change in First Morning Void Urine Albumin/Creatinine Ratio from baseline to each post baseline visit (Weeks 4, 8 and 12). [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]

• The proportion of subjects who achieve 2 consecutive >= 30% reductions in iPTH compared to baseline [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
• The mean percent change in iPTH over each visit [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
• The proportion of subjects who achieve 2 consecutive values within the K/DOQI target ranges for calcium and for phosphorus [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]

Safety and efficacy study using Paricalcitol capsules to decrease parathyroid hormone levels in children ages 10 to 16 with Chronic Kidney Disease.

The study consists of two parts. Part I is an open-label single-dose, non-fasting, multicenter study to evaluate the pharmacokinetics of paricalcitol capsules in 12 pediatric subjects ages 10 to 16 years with Chronic Kidney Disease Stages 3 and 4. Part II of this study will be conducted as a 12 week randomized double-blind, placebo-controlled study, followed by 12 weeks open-label treatment. Subjects active or enrolled under amendment 5 will enter a Follow-Up period and have study visits every 4 weeks until the final subject reaches Week 24. The objective of this multicenter study is to evaluate the safety and efficacy of paricalcitol capsules in decreasing serum intact parathyroid hormone levels to the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative target goals in 36 pediatric subjects ages 10 to 16 years with Chronic Kidney Disease Stages 3 and 4.

• Drug: Zemplar (paricalcitol) Capsules
  Group 1 - Paricalcitol capsules 1 - 3 mcg TIW (one to three Paricalcitol 1 mcg capsules TIW).
• Drug: Placebo capsules
  Group 2 - Placebo TIW (one to three placebo capsules TIW)

• Placebo Comparator: Paricalcitol capsules (1 - 3 mcg dose)
  Intervention: Drug: Zemplar (paricalcitol) Capsules
• Placebo Comparator: Placebo (1 -3 capsules per dose)
  Intervention: Drug: Placebo capsules

Inclusion Criteria:

• Male or female subjects' greater than or equal to 10 years old and less than or equal to 16 years old.
• 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).

• To satisfy the Screening criteria (for subjects that are currently on a Vitamin D Receptor Activator and need to complete a 2 to 4 week washout), the subject must have:

  • estimated Glomerular Filtration Rate between 15 to 59 mL/min/1.73 m2 (estimate by the Schwartz formula as outlined in Section 5.3.1.2).
  • 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 Vitamin 25D level that is greater than or equal to 30 ng/mL (Part II Only).

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.