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.
Department of Paediatric Nephrology and NIHR/Wellcome Trust Clinical Research Facility, Manchester Academic Health Science Centre, Royal Manchester Children's Hospital, University of Manchester, Oxford Road, Manchester, M13 9WL, UK. nicholas.webb@cmft.nhs.uk.
Nicholas J A
NJA
Webb
Pediatric Nephrology, Keck School of Medicine-Children's Hospital Los Angeles, Los Angeles, CA, USA.
Gary
G
Lerner
Division of Pediatric Nephrology, Children's Mercy Hospital, Kansas City, MO, USA.
Bradley A
BA
Warady
Center for Pediatric Nephrology, Cleveland Clinic Children's, Case Western Reserve University, Cleveland, OH, USA.
Katherine M
KM
Dell
Emory School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Larry A
LA
Greenbaum
Pediatric Nephrology, University Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain.
Gema
G
Ariceta
University Hospital Bonn, Bonn, Germany.
Bernd
B
Hoppe
AbbVie Inc., North Chicago, IL, USA.
Peter
P
Linde
AbbVie Inc., North Chicago, IL, USA.
Ho-Jin
HJ
Lee
AbbVie Inc., North Chicago, IL, USA.
Ann
A
Eldred
AbbVie Inc., North Chicago, IL, USA.
Matthew B
MB
Dufek
D000293:Adolescent; D050071:Bone Density Conservation Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D002648:Child; D004311:Double-Blind Method; D004872:Ergocalciferols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000139:chemically induced; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000209:etiology / Q000628:therapy*; D054559:Hyperphosphatemia / Q000097:blood / Q000139:chemically induced; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood*; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D004872:Ergocalciferols; D010281:Parathyroid Hormone; D010758:Phosphorus; C084656:paricalcitol; D002118:Calcium
Chronic kidney disease–mineral and bone disorder; Hypercalcemia; Paricalcitol; Pediatric; Secondary hyperparathyroidism