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): 133-142, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-32647975
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 mean Cmax, AUClast, and AUCinf 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hiperparatireoidismo Secundário
Tipo de estudo:
Etiology_studies
Limite:
Adolescent
/
Child
/
Child, preschool
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article