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Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study

BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an oral potassium binder approved to treat hyperkalemia in adults in a number of countries, including Japan. METHODS: This phase 2/3, randomized, double-blind, placebo-controlled, dose–response study (ClinicalTrials.gov: NCT03127644) was designed t...

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Autores principales: Kashihara, Naoki, Nishio, Toshiki, Osonoi, Takeshi, Saka, Yosuke, Imasawa, Toshiyuki, Ohtake, Takayasu, Mizuno, Hiroshi, Shibagaki, Yugo, 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/PMC7599176/
https://www.ncbi.nlm.nih.gov/pubmed/32779057
http://dx.doi.org/10.1007/s10157-020-01937-1
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author Kashihara, Naoki
Nishio, Toshiki
Osonoi, Takeshi
Saka, Yosuke
Imasawa, Toshiyuki
Ohtake, Takayasu
Mizuno, Hiroshi
Shibagaki, Yugo
Kim, Hyosung
Yajima, Toshitaka
Sarai, Nobuaki
author_facet Kashihara, Naoki
Nishio, Toshiki
Osonoi, Takeshi
Saka, Yosuke
Imasawa, Toshiyuki
Ohtake, Takayasu
Mizuno, Hiroshi
Shibagaki, Yugo
Kim, Hyosung
Yajima, Toshitaka
Sarai, Nobuaki
author_sort Kashihara, Naoki
collection PubMed
description BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an oral potassium binder approved to treat hyperkalemia in adults in a number of countries, including Japan. METHODS: This phase 2/3, randomized, double-blind, placebo-controlled, dose–response study (ClinicalTrials.gov: NCT03127644) was designed to determine the efficacy and safety of SZC in Japanese adults with hyperkalemia. Patients with serum potassium (sK(+)) concentrations ≥ 5.1– ≤ 6.5 mmol/L were randomized 1:1:1 to SZC 5 g, SZC 10 g, or placebo three times daily for 48 h (six doses total). The primary efficacy endpoint was the exponential rate of change in sK(+) over 48 h. The proportion of patients with normokalemia (sK(+) 3.5–5.0 mmol/L) at 48 h and adverse events (AEs) were also evaluated. RESULTS: Overall, 103 patients (mean age, 73.2 years; range 50–89 years) received SZC 5 g (n = 34), SZC 10 g (n = 36), or placebo (n = 33). The exponential rate of sK(+) change from 0 to 48 h versus placebo was − 0.00261 (SZC 5 g) and – 0.00496 (SZC 10 g; both P < 0.0001). At 48 h, the proportions of patients with normokalemia were 85.3%, 91.7%, and 15.2% with SZC 5 g, SZC 10 g, and placebo, respectively. No serious AEs were reported. Hypokalemia (sK(+)  < 3.5 mmol/L) occurred in two patients in the SZC 10 g group; normokalemia was re-established within 6 days and no treatment-related AEs were reported. CONCLUSION: SZC is effective and well tolerated in Japanese patients with hyperkalemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10157-020-01937-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-75991762020-11-10 Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study Kashihara, Naoki Nishio, Toshiki Osonoi, Takeshi Saka, Yosuke Imasawa, Toshiyuki Ohtake, Takayasu Mizuno, Hiroshi Shibagaki, Yugo Kim, Hyosung Yajima, Toshitaka Sarai, Nobuaki Clin Exp Nephrol Original Article BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an oral potassium binder approved to treat hyperkalemia in adults in a number of countries, including Japan. METHODS: This phase 2/3, randomized, double-blind, placebo-controlled, dose–response study (ClinicalTrials.gov: NCT03127644) was designed to determine the efficacy and safety of SZC in Japanese adults with hyperkalemia. Patients with serum potassium (sK(+)) concentrations ≥ 5.1– ≤ 6.5 mmol/L were randomized 1:1:1 to SZC 5 g, SZC 10 g, or placebo three times daily for 48 h (six doses total). The primary efficacy endpoint was the exponential rate of change in sK(+) over 48 h. The proportion of patients with normokalemia (sK(+) 3.5–5.0 mmol/L) at 48 h and adverse events (AEs) were also evaluated. RESULTS: Overall, 103 patients (mean age, 73.2 years; range 50–89 years) received SZC 5 g (n = 34), SZC 10 g (n = 36), or placebo (n = 33). The exponential rate of sK(+) change from 0 to 48 h versus placebo was − 0.00261 (SZC 5 g) and – 0.00496 (SZC 10 g; both P < 0.0001). At 48 h, the proportions of patients with normokalemia were 85.3%, 91.7%, and 15.2% with SZC 5 g, SZC 10 g, and placebo, respectively. No serious AEs were reported. Hypokalemia (sK(+)  < 3.5 mmol/L) occurred in two patients in the SZC 10 g group; normokalemia was re-established within 6 days and no treatment-related AEs were reported. CONCLUSION: SZC is effective and well tolerated in Japanese patients with hyperkalemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10157-020-01937-1) contains supplementary material, which is available to authorized users. Springer Singapore 2020-08-10 2020 /pmc/articles/PMC7599176/ /pubmed/32779057 http://dx.doi.org/10.1007/s10157-020-01937-1 Text en © The Author(s) 2020 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
Nishio, Toshiki
Osonoi, Takeshi
Saka, Yosuke
Imasawa, Toshiyuki
Ohtake, Takayasu
Mizuno, Hiroshi
Shibagaki, Yugo
Kim, Hyosung
Yajima, Toshitaka
Sarai, Nobuaki
Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study
title Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study
title_full Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study
title_fullStr Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study
title_full_unstemmed Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study
title_short Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study
title_sort correction of serum potassium with sodium zirconium cyclosilicate in japanese patients with hyperkalemia: a randomized, dose–response, phase 2/3 study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599176/
https://www.ncbi.nlm.nih.gov/pubmed/32779057
http://dx.doi.org/10.1007/s10157-020-01937-1
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