An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis.

Creator(s)

Winnie Y. Sohn
Anthony A. Portale
Isidro B. Salusky
Hao Zhang
Lucy L. Yan
Bella Ertik
Shahnaz Shahinfar
Edward Lee
Bastian Dehmel
Bradley A. Warady, Children's Mercy HospitalFollow

Document Type

Article

Publication Date

1-1-2019

Identifier

PMCID: PMC6244811 DOI: 10.1007/s00467-018-4054-8

Abstract

BACKGROUND: Calcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects.

METHODS: In this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) 2, 12, 48 h] and assessed for 72 h after dosing.

RESULTS: Median plasma cinacalcet tmax was 1 h (range 0.5-4.0 h); mean (SD) Cmax and AUClast were 2.83 (1.98) ng/mL and 11.8 (8.74) h*ng/mL, respectively; mean (SD) half-life (t1/2) was 3.70 (2.57) h. Dose adjustments, based upon body weight (mg/kg), minimized the effects of age, body weight, body surface area, and body mass index on cinacalcet PK. Reductions in serum PTH levels from baseline were observed at 2 to 8 h post-dose (median 10.8 and 29.6%, respectively), returned towards baseline by 12-72 h and were inversely related to changes in the plasma cinacalcet PK profile. Single-dose cinacalcet was well-tolerated with no unexpected safety findings and a PK/PD, safety profile similar to adults.

CONCLUSIONS: In conclusion, a single 0.25 mg/kg dose of cinacalcet was evaluated to be a safe starting dose in these children aged < 6 years.

Journal Title

Pediatric nephrology (Berlin, Germany)

Volume

34

Issue

1

First Page

145

Last Page

154

MeSH Keywords

Renal Insufficiency, Chronic; Cinacalcet; Parathyroid Hormone; Renal Dialysis; Hyperparathyroidism, Secondary; Child; Adolescent

Keywords

Calcimimetics; Chronic kidney disease; Cinacalcet; Parathyroid hormone; Pediatric dialysis patients; Secondary hyperparathyroidism

Comments

Erratum in

• Correction to: An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis. [Pediatr Nephrol. 2019]

Secondary source ID

• ClinicalTrials.gov/NCT01290029

Recommended Citation

Sohn WY, Portale AA, Salusky IB, et al. An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis [published correction appears in Pediatr Nephrol. 2019 Apr;34(4):739-740]. Pediatr Nephrol. 2019;34(1):145-154. doi:10.1007/s00467-018-4054-8