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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Singapore
2020
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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. |
format | Online Article Text |
id | pubmed-7599176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Singapore |
record_format | MEDLINE/PubMed |
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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