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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: Childr...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440538/
https://www.ncbi.nlm.nih.gov/pubmed/28332096
http://dx.doi.org/10.1007/s00467-017-3579-6
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author 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.
author_facet 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.
author_sort Webb, Nicholas J. A.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00467-017-3579-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-54405382017-06-08 Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease 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. Pediatr Nephrol Original Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00467-017-3579-6) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2017-03-22 2017 /pmc/articles/PMC5440538/ /pubmed/28332096 http://dx.doi.org/10.1007/s00467-017-3579-6 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
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.
Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease
title Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease
title_full Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease
title_fullStr Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease
title_full_unstemmed Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease
title_short Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease
title_sort efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440538/
https://www.ncbi.nlm.nih.gov/pubmed/28332096
http://dx.doi.org/10.1007/s00467-017-3579-6
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