Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan

Takashi Shigematsu,1 Ryutaro Shimazaki,2 Masafumi Fukagawa,3 Tadao Akizawa4 On behalf of the Evocalcet Study Group 1Department of Nephrology, Wakayama Medical University, Wakayama, Japan; 2R&D Division, Kyowa Hakko Kirin Co., Ltd., Chiyoda-ku, Tokyo, Japan; 3Department of Internal Medicine,...

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Autores principales:	Shigematsu T, Shimazaki R, Fukagawa M, Akizawa T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Calcimimetics evocalcet hemodialysis parathyroid hormone secondary hyperparathyroidism Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/010a1a592ce7469ea88768befb9f93b2
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spelling	oai:doaj.org-article:010a1a592ce7469ea88768befb9f93b22021-12-02T03:08:24ZPharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan1179-1438https://doaj.org/article/010a1a592ce7469ea88768befb9f93b22018-09-01T00:00:00Zhttps://www.dovepress.com/pharmacokinetics-of-evocalcet-in-secondary-hyperparathyroidism-patient-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Takashi Shigematsu,1 Ryutaro Shimazaki,2 Masafumi Fukagawa,3 Tadao Akizawa4 On behalf of the Evocalcet Study Group 1Department of Nephrology, Wakayama Medical University, Wakayama, Japan; 2R&D Division, Kyowa Hakko Kirin Co., Ltd., Chiyoda-ku, Tokyo, Japan; 3Department of Internal Medicine, Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan; 4Department of Medicine, Division of Nephrology, Showa University School of Medicine, Minato-ku, Tokyo, Japan Purpose: Cinacalcet is a positive allosteric modulator of calcium-sensing receptors in the parathyroid gland and an effective treatment for secondary hyperparathyroidism. However, this agent has considerable side effects and dosage limitations, which impair effective treatment. Therefore, we investigated the pharmacokinetics, pharmacodynamics, and safety of the novel calcimimetic, evocalcet.Patients and methods: This was a multicenter, open-label study of single oral doses of 1, 4, and 12 mg evocalcet using an intrapatient dose escalation protocol in 29 Japanese secondary hyperparathyroidism patients receiving hemodialysis. Pharmacokinetics was assessed by plasma evocalcet concentrations. Pharmacodynamic evaluations consisted of measuring intact parathyroid hormone, serum corrected calcium, and fibroblast growth factor 23 concentrations. Safety and tolerability were evaluated by the analysis of adverse events (AEs).Results: After a single 1-, 4-, or 12-mg dose, plasma evocalcet levels increased dose proportionally in a linear manner. Pharmacodynamic analyses showed that evocalcet effectively reduced intact parathyroid hormone and serum corrected calcium levels in a dose-dependent manner. AEs occurred in 31.0%, 28.6%, and 38.5% of patients receiving a single dose of 1, 4, or 12 mg, respectively. Most AEs were mild in severity.Conclusion: Evocalcet is effective in the short term, has linear pharmacokinetics, and is well tolerated as observed by the low incidence of AEs. Keywords: Calcimimetics, evocalcet, hemodialysis, parathyroid hormone, secondary hyperparathyroidismShigematsu TShimazaki RFukagawa MAkizawa TDove Medical PressarticleCalcimimeticsevocalcethemodialysisparathyroid hormonesecondary hyperparathyroidismTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 10, Pp 101-111 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Calcimimetics evocalcet hemodialysis parathyroid hormone secondary hyperparathyroidism Therapeutics. Pharmacology RM1-950
spellingShingle	Calcimimetics evocalcet hemodialysis parathyroid hormone secondary hyperparathyroidism Therapeutics. Pharmacology RM1-950 Shigematsu T Shimazaki R Fukagawa M Akizawa T Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan
description	Takashi Shigematsu,1 Ryutaro Shimazaki,2 Masafumi Fukagawa,3 Tadao Akizawa4 On behalf of the Evocalcet Study Group 1Department of Nephrology, Wakayama Medical University, Wakayama, Japan; 2R&D Division, Kyowa Hakko Kirin Co., Ltd., Chiyoda-ku, Tokyo, Japan; 3Department of Internal Medicine, Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan; 4Department of Medicine, Division of Nephrology, Showa University School of Medicine, Minato-ku, Tokyo, Japan Purpose: Cinacalcet is a positive allosteric modulator of calcium-sensing receptors in the parathyroid gland and an effective treatment for secondary hyperparathyroidism. However, this agent has considerable side effects and dosage limitations, which impair effective treatment. Therefore, we investigated the pharmacokinetics, pharmacodynamics, and safety of the novel calcimimetic, evocalcet.Patients and methods: This was a multicenter, open-label study of single oral doses of 1, 4, and 12 mg evocalcet using an intrapatient dose escalation protocol in 29 Japanese secondary hyperparathyroidism patients receiving hemodialysis. Pharmacokinetics was assessed by plasma evocalcet concentrations. Pharmacodynamic evaluations consisted of measuring intact parathyroid hormone, serum corrected calcium, and fibroblast growth factor 23 concentrations. Safety and tolerability were evaluated by the analysis of adverse events (AEs).Results: After a single 1-, 4-, or 12-mg dose, plasma evocalcet levels increased dose proportionally in a linear manner. Pharmacodynamic analyses showed that evocalcet effectively reduced intact parathyroid hormone and serum corrected calcium levels in a dose-dependent manner. AEs occurred in 31.0%, 28.6%, and 38.5% of patients receiving a single dose of 1, 4, or 12 mg, respectively. Most AEs were mild in severity.Conclusion: Evocalcet is effective in the short term, has linear pharmacokinetics, and is well tolerated as observed by the low incidence of AEs. Keywords: Calcimimetics, evocalcet, hemodialysis, parathyroid hormone, secondary hyperparathyroidism
format	article
author	Shigematsu T Shimazaki R Fukagawa M Akizawa T
author_facet	Shigematsu T Shimazaki R Fukagawa M Akizawa T
author_sort	Shigematsu T
title	Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan
title_short	Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan
title_full	Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan
title_fullStr	Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan
title_full_unstemmed	Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan
title_sort	pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in japan
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/010a1a592ce7469ea88768befb9f93b2
work_keys_str_mv	AT shigematsut pharmacokineticsofevocalcetinsecondaryhyperparathyroidismpatientsreceivinghemodialysisfirstinpatientclinicaltrialinjapan AT shimazakir pharmacokineticsofevocalcetinsecondaryhyperparathyroidismpatientsreceivinghemodialysisfirstinpatientclinicaltrialinjapan AT fukagawam pharmacokineticsofevocalcetinsecondaryhyperparathyroidismpatientsreceivinghemodialysisfirstinpatientclinicaltrialinjapan AT akizawat pharmacokineticsofevocalcetinsecondaryhyperparathyroidismpatientsreceivinghemodialysisfirstinpatientclinicaltrialinjapan
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Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan

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