Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease
Webb, Nicholas J. A. (Royal Manchester Children's Hospital, Manchester, UK)
Lerner, Gary (Keck School of Medicine-Children's Hospital Los Angeles, USA)
Warady, Bradley A. (Children's Mercy Hospital, Kansas City, USA.)
Dell, Katherine M. (Cleveland Clinic Children's, USA)
Greenbaum, Larry A. (Emory School of Medicine and Children's Healthcare of Atlanta, USA.)
Ariceta Iraola, Gema (Hospital Universitari Vall d'Hebron)
Hoppe, Bernd (University Hospital Bonn (Bonn, Alemanya))
Linde, Peter (AbbVie Inc., North Chicago, USA)
Lee, Ho-Jin (AbbVie Inc., North Chicago, USA)
Eldred, Ann (AbbVie Inc., North Chicago, USA)
Dufek, Matthew B. (AbbVie Inc., North Chicago, USA)
Universitat Autònoma de Barcelona

Fecha:	2017
Resumen:	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. 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. 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. 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. The online version of this article (doi:10. 1007/s00467-017-3579-6) contains supplementary material, which is available to authorized users.
Nota:	Altres ajuts: AbbVie provided funding for the stage 3/4 and stage 5 studies and was involved in the study designs, study execution, collection, analysis, and interpretation of data, and the writing, review, and approval of the report, as well as the decision to submit the manuscript for publication. All authors had access to study results, and Professor Nicholas J. A. Webb takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors had the final decision to submit the publication. The study was overseen by a data review committee.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Secondary hyperparathyroidism ; Paricalcitol ; Chronic kidney disease-mineral and bone disorder ; Pediatric ; Hypercalcemia
Publicado en:	Pediatric Nephrology, Vol. 32 (march 2017) , p. 1221-1232, ISSN 1432-198X

DOI: 10.1007/s00467-017-3579-6
PMID: 28332096

12 p, 1.5 MB

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