Universität zu Köln

Sohn, Winnie, Salusky, Isidro B., Schmitt, Claus Peter, Taylan, Christina, Vande Walle, Johan, Ngang, Jude, Yan, Lucy, Kroenke, Mark and Warady, Bradley A. (2021). Phase 1, single-dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of etelcalcetide in pediatric patients with secondary hyperparathyroidism receiving hemodialysis. Pediatr. Nephrol., 36 (1). S. 133 - 143. NEW YORK: SPRINGER. ISSN 1432-198X

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Abstract

Background Data on the safety, efficacy of etelcalcetide in children with secondary hyperparathyroidism (sHPT) are limited. Methods This phase 1 study (NCT02833857) evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) of single-dose etelcalcetide (0.035 mg/kg intravenously) in pediatric hemodialysis patients (two cohorts; 1: 12-< 18 years; 2: 2-< 12 years). Treatment-emergent adverse events (AEs), PK/PD were assessed post-dose on D1 at 10 min and 4 h, on multiple days until D10, and at end of study (D30). Results Etelcalcetide administered to 11 patients (mean [SD] age 10.3 [4.3] years; cohort 1,n= 6; cohort 2,n= 5) was well tolerated. AEs were consistent with established safety profiles in adults. Two patients (1 per cohort) reported treatment-related AEs (cohort 1: hypocalcemia; cohort 2: headache, paresthesia, vomiting). No serious AEs or deaths were reported. Mean serum corrected calcium (cCa) for all patients was maintained > 2.25 mmol/L. After etelcalcetide dosing, PK exposures declined, with meanC(max), AUC(last), and AUC(inf)exposures higher in cohort 1. Median percent change in serum intact parathyroid hormone (iPTH) from baseline (cohort 1: 51.2 pmol/L; cohort 2: 84.0 pmol/L) reached the nadir on D1 at 4 h (cohort 1: - 33.4%; cohort 2: - 64.2%). Mean total calcium and cCa reached nadirs on D3 at 2.39 mmol/L, and ionized Ca on D1 at 4 h. Conclusions Single-dose etelcalcetide (0.035 mg/kg) was well tolerated with expected PK and safety profiles. Overall pattern of changes in serum iPTH and serum calcium was similar between cohorts and consistent with expected responses to etelcalcetide.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sohn, Winnie UNSPECIFIED UNSPECIFIED UNSPECIFIED Salusky, Isidro B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitt, Claus Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Taylan, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Vande Walle, Johan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ngang, Jude UNSPECIFIED UNSPECIFIED UNSPECIFIED Yan, Lucy UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Warady, Bradley A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-326663
DOI:	10.1007/s00467-020-04599-z
Journal or Publication Title:	Pediatr. Nephrol.
Volume:	36
Number:	1
Page Range:	S. 133 - 143
Date:	2021
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-198X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC KIDNEY-DISEASE; FIBROBLAST GROWTH FACTOR-23; SERUM PARATHYROID-HORMONE; VITAMIN-D ANALOGS; AMG 416; CHILDREN; CINACALCET; PEPTIDE Multiple languages Pediatrics; Urology & Nephrology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32666