Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease.

BACKGROUND Elevated intact parathyroid hormone (iPTH) levels can contribute to morbidity and mortality in children with chronic kidney disease (CKD). We evaluated the pharmacokinetics, efficacy, and safety of oral paricalcitol in reducing iPTH levels in children with stages 3-5 CKD. METHODS Children aged 10-16 years with stages 3-5 CKD were enrolled in two phase 3 studies. The stage 3/4 CKD study characterized paricalcitol pharmacokinetics and compared the efficacy and safety of paricalcitol with placebo followed by an open-label period. The stage 5 CKD study evaluated the efficacy and safety of paricalcitol (no comparator) in children with stage 5 CKD undergoing dialysis. RESULTS In the stage 3/4 CKD study, mean peak plasma concentration and area under the time curve from zero to infinity were 0.13 ng/mL and 2.87 ng•h/((or ng×h/))mL, respectively, for 12 children who received 3 μg paricalcitol. Thirty-six children were randomized to paricalcitol or placebo; 27.8% of the paricalcitol group achieved two consecutive iPTH reductions of ≥30% from baseline versus none of the placebo group (P = 0.045). Adverse events were higher in children who received placebo than in those administered paricalcitol during the double-blind treatment (88.9 vs. 38.9%; P = 0.005). In the stage 5 CKD study, eight children (61.5%) had two consecutive iPTH reductions of ≥30% from baseline, and five (38.5%) had two consecutive iPTH values of between 150 and 300 pg/mL. Clinically meaningful hypercalcemia occurred in 21% of children. CONCLUSIONS Oral paricalcitol in children aged 10-16 years with stages 3-5 CKD reduced iPTH levels and the treatment was well tolerated. Results support an initiating dose of 1 μg paricalcitol 3 times weekly in children aged 10-16 years.