PMID- 32647975
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20211214
IS  - 1432-198X (Electronic)
IS  - 0931-041X (Linking)
VI  - 36
IP  - 1
DP  - 2021 Jan
TI  - Phase 1, single-dose study to assess the safety, tolerability, pharmacokinetics, 
      and pharmacodynamics of etelcalcetide in pediatric patients with secondary 
      hyperparathyroidism receiving hemodialysis.
PG  - 133-142
LID - 10.1007/s00467-020-04599-z [doi]
AB  - 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 C(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.
FAU - Sohn, Winnie
AU  - Sohn W
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Salusky, Isidro B
AU  - Salusky IB
AD  - Division of Pediatric Nephrology, David Geffen School of Medicine at UCLA, Los 
      Angeles, CA, USA.
FAU - Schmitt, Claus Peter
AU  - Schmitt CP
AD  - Center for Pediatric and Adolescent Medicine, Heidelberg, Germany.
FAU - Taylan, Christina
AU  - Taylan C
AD  - University Hospital of Cologne, Koln, Germany.
FAU - Walle, Johan Vande
AU  - Walle JV
AD  - UZGent, Gent, Belgium.
FAU - Ngang, Jude
AU  - Ngang J
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Yan, Lucy
AU  - Yan L
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Kroenke, Mark
AU  - Kroenke M
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Warady, Bradley A
AU  - Warady BA
AUID- ORCID: 0000-0003-1812-6587
AD  - Children's Mercy Kansas City, Kansas City, MO, USA. bwarady@cmh.edu.
LA  - eng
SI  - ClinicalTrials.gov/NCT02833857
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200709
PL  - Germany
TA  - Pediatr Nephrol
JT  - Pediatric nephrology (Berlin, Germany)
JID - 8708728
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Peptides)
RN  - 72PT5993DU (etelcalcetide hydrochloride)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adolescent
MH  - Calcium
MH  - Child
MH  - Child, Preschool
MH  - Humans
MH  - *Hyperparathyroidism, Secondary/drug therapy/etiology
MH  - Parathyroid Hormone
MH  - Peptides
MH  - Renal Dialysis/adverse effects
MH  - Renal Insufficiency, Chronic
OTO - NOTNLM
OT  - Children
OT  - Chronic kidney disease
OT  - Etelcalcetide
OT  - Hemodialysis
OT  - Pediatric population
OT  - Secondary hyperparathyroidism
EDAT- 2020/07/11 06:00
MHDA- 2021/12/15 06:00
CRDT- 2020/07/11 06:00
PHST- 2019/11/21 00:00 [received]
PHST- 2020/05/04 00:00 [accepted]
PHST- 2020/04/29 00:00 [revised]
PHST- 2020/07/11 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/07/11 06:00 [entrez]
AID - 10.1007/s00467-020-04599-z [pii]
AID - 10.1007/s00467-020-04599-z [doi]
PST - ppublish
SO  - Pediatr Nephrol. 2021 Jan;36(1):133-142. doi: 10.1007/s00467-020-04599-z. Epub 
      2020 Jul 9.