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A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia

BACKGROUND: Hyperkalemia is associated with many chronic diseases and renin-angiotensin-aldosterone system inhibitor therapy. Sodium zirconium cyclosilicate (SZC), an oral, highly selective cation-exchanger, is approved for the treatment of hyperkalemia. METHODS: This phase 3, multicenter, open-labe...

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Autores principales: Kashihara, Naoki, Yamasaki, Yoshimitsu, Osonoi, Takeshi, Harada, Hiromasa, Shibagaki, Yugo, Zhao, June, Kim, Hyosung, Yajima, Toshitaka, Sarai, Nobuaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880936/
https://www.ncbi.nlm.nih.gov/pubmed/33098526
http://dx.doi.org/10.1007/s10157-020-01972-y
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author Kashihara, Naoki
Yamasaki, Yoshimitsu
Osonoi, Takeshi
Harada, Hiromasa
Shibagaki, Yugo
Zhao, June
Kim, Hyosung
Yajima, Toshitaka
Sarai, Nobuaki
author_facet Kashihara, Naoki
Yamasaki, Yoshimitsu
Osonoi, Takeshi
Harada, Hiromasa
Shibagaki, Yugo
Zhao, June
Kim, Hyosung
Yajima, Toshitaka
Sarai, Nobuaki
author_sort Kashihara, Naoki
collection PubMed
description BACKGROUND: Hyperkalemia is associated with many chronic diseases and renin-angiotensin-aldosterone system inhibitor therapy. Sodium zirconium cyclosilicate (SZC), an oral, highly selective cation-exchanger, is approved for the treatment of hyperkalemia. METHODS: This phase 3, multicenter, open-label, single-arm, flexible-dose study assessed the safety and efficacy of SZC in Japanese patients with hyperkalemia during a correction phase of up to 3 days and long-term (1 year) maintenance phase (NCT03172702). RESULTS: Overall, 150 patients received treatment during both study phases; the study population was generally representative of hyperkalemic Japanese patients in clinical practice. Most patients (78.7%) had three doses of SZC during the correction phase. All but one patient received SZC for ≤ 48 h before transitioning to the maintenance phase. In the maintenance phase, mean (standard deviation; SD) exposure to the study drug was 319.4 (98.1) days and mean (SD) dose was 7.38 (2.85) g/day. Adverse events (AEs) were reported in 131 patients (87.3%); most were mild. The most common treatment-related AEs as evaluated by investigators were constipation (6.7%), peripheral edema (4.0%), and hypertension (2.7%). In the correction phase, 78.7% of patients were normokalemic at 24 h and 98.7% within 48 h; ≥ 65.5% maintained normokalemia throughout the maintenance phase. CONCLUSION: After a year of exposure, SZC treatment was well tolerated by Japanese patients and potassium levels were well controlled. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10157-020-01972-y.
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spelling pubmed-78809362021-02-18 A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia Kashihara, Naoki Yamasaki, Yoshimitsu Osonoi, Takeshi Harada, Hiromasa Shibagaki, Yugo Zhao, June Kim, Hyosung Yajima, Toshitaka Sarai, Nobuaki Clin Exp Nephrol Original Article BACKGROUND: Hyperkalemia is associated with many chronic diseases and renin-angiotensin-aldosterone system inhibitor therapy. Sodium zirconium cyclosilicate (SZC), an oral, highly selective cation-exchanger, is approved for the treatment of hyperkalemia. METHODS: This phase 3, multicenter, open-label, single-arm, flexible-dose study assessed the safety and efficacy of SZC in Japanese patients with hyperkalemia during a correction phase of up to 3 days and long-term (1 year) maintenance phase (NCT03172702). RESULTS: Overall, 150 patients received treatment during both study phases; the study population was generally representative of hyperkalemic Japanese patients in clinical practice. Most patients (78.7%) had three doses of SZC during the correction phase. All but one patient received SZC for ≤ 48 h before transitioning to the maintenance phase. In the maintenance phase, mean (standard deviation; SD) exposure to the study drug was 319.4 (98.1) days and mean (SD) dose was 7.38 (2.85) g/day. Adverse events (AEs) were reported in 131 patients (87.3%); most were mild. The most common treatment-related AEs as evaluated by investigators were constipation (6.7%), peripheral edema (4.0%), and hypertension (2.7%). In the correction phase, 78.7% of patients were normokalemic at 24 h and 98.7% within 48 h; ≥ 65.5% maintained normokalemia throughout the maintenance phase. CONCLUSION: After a year of exposure, SZC treatment was well tolerated by Japanese patients and potassium levels were well controlled. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10157-020-01972-y. Springer Singapore 2020-10-24 2021 /pmc/articles/PMC7880936/ /pubmed/33098526 http://dx.doi.org/10.1007/s10157-020-01972-y Text en © The Author(s) 2020, corrected publication 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Article
Kashihara, Naoki
Yamasaki, Yoshimitsu
Osonoi, Takeshi
Harada, Hiromasa
Shibagaki, Yugo
Zhao, June
Kim, Hyosung
Yajima, Toshitaka
Sarai, Nobuaki
A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia
title A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia
title_full A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia
title_fullStr A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia
title_full_unstemmed A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia
title_short A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia
title_sort phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in japanese subjects with hyperkalemia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880936/
https://www.ncbi.nlm.nih.gov/pubmed/33098526
http://dx.doi.org/10.1007/s10157-020-01972-y
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