Abstract
BackgroundElevated 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.MethodsChildren 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.ResultsIn 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.ConclusionsOral 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.
Highlights
Chronic kidney disease-mineral and bone disorder (CKDMBD) is a common complication of progressive chronic kidney disease (CKD) [1]
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)
Children receiving hemodialysis treated with intravenous paricalcitol had a statistically significant decrease in intact parathyroid hormone (iPTH) levels from baseline compared with their counterparts receiving placebo (164 pg/mL decrease vs. 238 pg/mL increase, respectively; P = 0.03) [17]
Summary
No statistically significant differences were observed in baseline clinical characteristics (sex, age, weight, race, and ethnicity) between children enrolled in the placebo and paricalcitol arms of Part 2. No statistically significant differences were observed in the baseline vital signs or laboratory values between the placebo and paricalcitol groups. The pharmacokinetics of oral paricalcitol following a 3 μg dose were similar between children with stages 3 and 4 CKD (Fig. 2; Table 2). During the double-blind period of the stage 3/4 CKD study, five of the 18 children (27.8%) in the paricalcitol group achieved the primary outcome of two consecutive reductions of ≥30% from baseline in iPTH levels, compared with no
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