A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism
The pharmacokinetics, pharmacodynamics, and safety and tolerability profile of etelcalcetide (ONO-5163/AMG 416), a novel, i.v., long-acting calcium-sensing receptor agonist, were studied in Japanese hemodialysis patients with secondary hyperparathyroidism. Methods: This multicenter, randomized, doub...
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doaj-08404379244441e88d3a14ecd0f7ec8d2020-11-24T22:13:52ZengElsevierKidney International Reports2468-02492017-07-012463464410.1016/j.ekir.2017.01.016A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary HyperparathyroidismKeitaro Yokoyama0Masafumi Fukagawa1Takashi Shigematsu2Takashi Akiba3Akifumi Fujii4Akinori Yamauchi5Motoi Odani6Tadao Akizawa7Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, JapanDivision of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, JapanDepartment of Nephrology, Wakayama Medical University, Wakayama, JapanSekikawa Hospital, Tokyo, JapanClinical Development Planning, Ono Pharmaceutical Co., Ltd., Osaka, JapanClinical Pharmacology, Ono Pharmaceutical Co., Ltd., Osaka, JapanData Science, Ono Pharmaceutical Co., Ltd., Osaka, JapanDivision of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, JapanThe pharmacokinetics, pharmacodynamics, and safety and tolerability profile of etelcalcetide (ONO-5163/AMG 416), a novel, i.v., long-acting calcium-sensing receptor agonist, were studied in Japanese hemodialysis patients with secondary hyperparathyroidism. Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisted of a single dose part and a multiple dose (3 times weekly for 4 weeks) part. Major inclusion criteria were hemodialysis for at least 90 days, serum intact parathyroid hormone (iPTH) ≥ 300 pg/ml, and serum albumin-corrected Ca (cCa) ≥ 9.0 mg/dl. There were 3 single-dose cohorts (n = 6 each) randomized 2:1 to 5, 10, or 20 mg etelcalcetide or placebo, and 2 multiple-dose cohorts (n = 11 each) randomized 8:3 to 2.5 or 5 mg etelcalcetide or placebo. Results: Etelcalcetide plasma concentration decreased rapidly after i.v. administration, generally remained stable from 24 hours postdose to the next dialysis, and then decreased by dialysis. Etelcalcetide exposure increased dose proportionally. Etelcalcetide plasma predialysis concentration reached almost steady state at week 4. A single dose of etelcalcetide dose-dependently reduced serum iPTH in 30 minutes, and the reduction reached a plateau at 1 hour that lasted until 8 hours. The percent change from baseline serum iPTH thereafter showed a trend to gradually decrease; it was still −30% or greater on day 3. Similar results were obtained at the last injection (days 27–29) of the multiple dose. The effect of the multiple dose was sustained during the interdialytic period. Etelcalcetide decreased serum cCa in a more gradual but dose-dependent and sustained manner. Discussion: Etelcalcetide dose-dependently reduced serum iPTH and serum cCa. Moreover, the effect was sustained in the interdialytic period.http://www.sciencedirect.com/science/article/pii/S2468024917300414calcium-sensing receptor agonist (calcimimetics)clinical trialetelcalcetide (ONO-5163/AMG 416)secondary hyperparathyroidism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Keitaro Yokoyama Masafumi Fukagawa Takashi Shigematsu Takashi Akiba Akifumi Fujii Akinori Yamauchi Motoi Odani Tadao Akizawa |
spellingShingle |
Keitaro Yokoyama Masafumi Fukagawa Takashi Shigematsu Takashi Akiba Akifumi Fujii Akinori Yamauchi Motoi Odani Tadao Akizawa A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism Kidney International Reports calcium-sensing receptor agonist (calcimimetics) clinical trial etelcalcetide (ONO-5163/AMG 416) secondary hyperparathyroidism |
author_facet |
Keitaro Yokoyama Masafumi Fukagawa Takashi Shigematsu Takashi Akiba Akifumi Fujii Akinori Yamauchi Motoi Odani Tadao Akizawa |
author_sort |
Keitaro Yokoyama |
title |
A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism |
title_short |
A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism |
title_full |
A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism |
title_fullStr |
A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism |
title_full_unstemmed |
A Single- and Multiple-Dose, Multicenter Study of Etelcalcetide in Japanese Hemodialysis Patients With Secondary Hyperparathyroidism |
title_sort |
single- and multiple-dose, multicenter study of etelcalcetide in japanese hemodialysis patients with secondary hyperparathyroidism |
publisher |
Elsevier |
series |
Kidney International Reports |
issn |
2468-0249 |
publishDate |
2017-07-01 |
description |
The pharmacokinetics, pharmacodynamics, and safety and tolerability profile of etelcalcetide (ONO-5163/AMG 416), a novel, i.v., long-acting calcium-sensing receptor agonist, were studied in Japanese hemodialysis patients with secondary hyperparathyroidism.
Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisted of a single dose part and a multiple dose (3 times weekly for 4 weeks) part. Major inclusion criteria were hemodialysis for at least 90 days, serum intact parathyroid hormone (iPTH) ≥ 300 pg/ml, and serum albumin-corrected Ca (cCa) ≥ 9.0 mg/dl. There were 3 single-dose cohorts (n = 6 each) randomized 2:1 to 5, 10, or 20 mg etelcalcetide or placebo, and 2 multiple-dose cohorts (n = 11 each) randomized 8:3 to 2.5 or 5 mg etelcalcetide or placebo.
Results: Etelcalcetide plasma concentration decreased rapidly after i.v. administration, generally remained stable from 24 hours postdose to the next dialysis, and then decreased by dialysis. Etelcalcetide exposure increased dose proportionally. Etelcalcetide plasma predialysis concentration reached almost steady state at week 4. A single dose of etelcalcetide dose-dependently reduced serum iPTH in 30 minutes, and the reduction reached a plateau at 1 hour that lasted until 8 hours. The percent change from baseline serum iPTH thereafter showed a trend to gradually decrease; it was still −30% or greater on day 3. Similar results were obtained at the last injection (days 27–29) of the multiple dose. The effect of the multiple dose was sustained during the interdialytic period. Etelcalcetide decreased serum cCa in a more gradual but dose-dependent and sustained manner.
Discussion: Etelcalcetide dose-dependently reduced serum iPTH and serum cCa. Moreover, the effect was sustained in the interdialytic period. |
topic |
calcium-sensing receptor agonist (calcimimetics) clinical trial etelcalcetide (ONO-5163/AMG 416) secondary hyperparathyroidism |
url |
http://www.sciencedirect.com/science/article/pii/S2468024917300414 |
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