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...

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Published in:Pediatric nephrology (Berlin, West) West), 2017-07, Vol.32 (7), p.1221-1232
Main Authors: Webb, Nicholas J. A., Lerner, Gary, Warady, Bradley A., Dell, Katherine M., Greenbaum, Larry A., Ariceta, Gema, Hoppe, Bernd, Linde, Peter, Lee, Ho-Jin, Eldred, Ann, Dufek, Matthew B.
Format: Article
Language:English
Subjects:
Adolescent
Bone Density Conservation Agents - pharmacokinetics
Bone Density Conservation Agents - therapeutic use
Calcium - blood
Care and treatment
Child
Children
Chronic kidney failure
Diagnosis
Dialysis
Dosage and administration
Double-Blind Method
Ergocalciferols - pharmacokinetics
Ergocalciferols - therapeutic use
Female
Health aspects
Humans
Hypercalcemia
Hypercalcemia - blood
Hypercalcemia - chemically induced
Hyperparathyroidism, Secondary - blood
Hyperparathyroidism, Secondary - etiology
Hyperparathyroidism, Secondary - therapy
Hyperphosphatemia - blood
Hyperphosphatemia - chemically induced
Kidney diseases
Kidney Failure, Chronic - blood
Kidney Failure, Chronic - complications
Kidney Failure, Chronic - therapy
Kidney transplantation
Male
Medicine
Medicine & Public Health
Morbidity
Nephrology
Original
Original Article
Parathyroid
Parathyroid hormone
Parathyroid Hormone - blood
Paricalcitol
Pediatric research
Pediatrics
Pharmacokinetics
Phosphorus - blood
Renal Dialysis
Treatment Outcome
Urology
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Summary: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.
ISSN:0931-041X
1432-198X
DOI:10.1007/s00467-017-3579-6