Phase 1, single-dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of etelcalcetide in pediatric patients with secondary hyperparathyroidism receiving hemodialysis.
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.
Pediatric nephrology (Berlin, Germany)
Children; Chronic kidney disease; Etelcalcetide; Hemodialysis; Pediatric population; Secondary hyperparathyroidism
Sohn, W., Salusky, I. B., Schmitt, C., Taylan, C., Walle, J., Ngang, J., Yan, L., Kroenke, M., Warady, B. A. Phase 1, single-dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of etelcalcetide in pediatric patients with secondary hyperparathyroidism receiving hemodialysis. Pediatric nephrology (Berlin, Germany) 36, 133-142 (2021).