PMID- 34774334
OWN - NLM
STAT- MEDLINE
DCOM- 20220128
LR  - 20220128
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 43
IP  - 11
DP  - 2021 Nov
TI  - A Phase I, Multiple-Dose, Randomized, Double-Blind, Placebo-Controlled Study to 
      Evaluate Pharmacokinetics, Safety, and Tolerability of Etelcalcetide Administered 
      Intravenously to Chinese Patients With Chronic Kidney Disease Undergoing 
      Hemodialysis.
PG  - 2013-2023
LID - S0149-2918(21)00392-1 [pii]
LID - 10.1016/j.clinthera.2021.09.019 [doi]
AB  - PURPOSE: This study reports data from the first evaluation of etelcalcetide 
      treatment in Chinese adults with chronic kidney disease and secondary 
      hyperparathyroidism. METHODS: This phase I, randomized study compared 
      thrice-weekly etelcalcetide (5 mg per dose intravenously) and placebo in 33 
      Chinese adults (aged 18-70 years) receiving hemodialysis. Patients in both 
      treatment groups received standard-of-care treatment with a total of 12 doses of 
      the investigational product during a 4-week treatment period, followed by 4 weeks 
      of washout and follow-up. Pharmacokinetic (PK) parameters (primary endpoint), 
      tolerability (secondary endpoint), and changes in intact parathyroid hormone 
      (iPTH) and corrected calcium (cCa) concentrations (exploratory endpoints) were 
      assessed. PK parameters, ie, the maximum plasma concentration (C(max)()) and area 
      under the plasma concentration-time curve (AUC(0-last)), assessed over the 
      interdialytic interval following the first and last doses were evaluated. The 
      incidence of treatment-emergent adverse events (AEs) and anti-etelcalcetide 
      antibodies was assessed. FINDINGS: Etelcalcetide administered to 25 patients was 
      compared with placebo administered to 8 patients. Etelcalcetide exposure, 
      assessed by C(max) and AUC(0-last), increased after multiple-dose administration 
      of etelcalcetide through day 27, with a mean (SD) accumulation ratio of 3.02 
      (0.61) based on AUC. At least one AE was reported for all patients in the 
      etelcalcetide group and for 87.5% of patients in the placebo group. Serious AEs 
      were reported in 12% of patients in the etelcalcetide group only. No deaths 
      occurred, and a single discontinuation because of patient withdrawal of consent 
      was reported in the etelcalcetide group. Preexisting anti-etelcalcetide 
      antibodies were detected in one patient. The mean serum cCa level for all 
      patients was maintained at >1.75 mmol/L. The iPTH and cCa concentrations 
      decreased as expected, and a maximum mean decrease from baseline of 35.13% in 
      iPTH levels was detected on day 27. IMPLICATIONS: Multiple doses of 5 mg 
      etelcalcetide were well tolerated, and observed etelcalcetide PK and safety 
      profiles were similar to those in reports in adults of ethnicities other than 
      Chinese. Changes in serum iPTH and serum calcium levels were consistent with 
      expected responses to etelcalcetide. ClinicalTrials.gov identifier: NCT03283098.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Xing, Changying
AU  - Xing C
AD  - Jiangsu Province Hospital, Nanjing, People's Republic of China. Electronic 
      address: cyxing62@126.com.
FAU - Chen, Jing
AU  - Chen J
AD  - Huashan Hospital of Fudan University, Shanghai, People's Republic of China.
FAU - Zuo, Li
AU  - Zuo L
AD  - Peking University Peoples' Hospital, Beijing, People's Republic of China.
FAU - Fang, Yi
AU  - Fang Y
AD  - Peking University Peoples' Hospital, Beijing, People's Republic of China.
FAU - Ding, Xiaoqiang
AU  - Ding X
AD  - Zhongshan Hospital of Fudan University, Shanghai, People's Republic of China.
FAU - Ni, Zhaohui
AU  - Ni Z
AD  - Renji Hospital Shanghai, Jiao Tong University School of Medicine, Shanghai, 
      People's Republic of China.
FAU - Kong, Carol
AU  - Kong C
AD  - Labcorp Pharmaceutical Research and Development (Shanghai) Co. Ltd., Shanghai, 
      China.
FAU - Shi, Guiling
AU  - Shi G
AD  - Labcorp Pharmaceutical Research and Development (Shanghai) Co. Ltd., Shanghai, 
      China.
FAU - Lu, Hong
AU  - Lu H
AD  - China Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd., Beijing, China.
FAU - Hellawell, Jennifer
AU  - Hellawell J
AD  - Amgen Inc., Thousand Oaks, California.
FAU - Cheng, Sunfa
AU  - Cheng S
AD  - Amgen Inc., Thousand Oaks, California.
FAU - Sohn, Winnie
AU  - Sohn W
AD  - Amgen Inc., Thousand Oaks, California. Electronic address: wkim@amgen.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT03283098
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20211111
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Peptides)
RN  - 72PT5993DU (etelcalcetide hydrochloride)
SB  - IM
MH  - Adult
MH  - China
MH  - Double-Blind Method
MH  - Humans
MH  - *Peptides
MH  - Renal Dialysis
MH  - *Renal Insufficiency, Chronic/complications/therapy
OTO - NOTNLM
OT  - Chinese adults
OT  - chronic kidney disease
OT  - etelcalcetide
OT  - hemodialysis
OT  - secondary hyperparathyroidism
EDAT- 2021/11/15 06:00
MHDA- 2022/01/29 06:00
CRDT- 2021/11/14 20:36
PHST- 2021/05/20 00:00 [received]
PHST- 2021/08/26 00:00 [revised]
PHST- 2021/09/25 00:00 [accepted]
PHST- 2021/11/15 06:00 [pubmed]
PHST- 2022/01/29 06:00 [medline]
PHST- 2021/11/14 20:36 [entrez]
AID - S0149-2918(21)00392-1 [pii]
AID - 10.1016/j.clinthera.2021.09.019 [doi]
PST - ppublish
SO  - Clin Ther. 2021 Nov;43(11):2013-2023. doi: 10.1016/j.clinthera.2021.09.019. Epub 
      2021 Nov 11.