Safety and Efficacy of Paricalcitol Capsules in Decreasing Serum Parathyroid Hormone Levels in Children Aged 10-16 With Chronic Kidney Disease (CKD)
Condition: Chronic Kidney Disease Stage 3 and 4
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Intervention: Paricalcitol; Placebo
Intervention description: Paricalcitol capsules taken with water.; Placebo capsules taken with water
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 47.0
Sex: All
Minimum age: 10 Years
Maximum age: 16 Years
Healthy volunteers: No
Keywords: Reduction of parathyroid hormone levels in pediatric patients with Chronic Kidney Disease Stage 3 and 4

Summary:

      Part 1: To determine the safety, tolerability, and pharmacokinetics of a single dose of 3 μg
      paricalcitol capsules in children ages 10 to 16 years with moderate to severe chronic kidney
      disease (CKD Stages 3 and 4).

      Part 2: To determine the safety and efficacy of paricalcitol capsules as compared to placebo
      in decreasing serum intact parathyroid hormone (iPTH) in children ages 10 to 16 years with
      moderate to severe chronic kidney disease with an initial 12 weeks of double-blinded study
      drug followed by a minimum of 12 weeks of open-label active drug.
    

Eligibility criteria:

        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.