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

Naoki Kashihara, Toshiki Nishio, Takeshi Osonoi, Yosuke Saka, Toshiyuki Imasawa, Takayasu Ohtake, Hiroshi Mizuno, Yugo Shibagaki, Hyosung Kim, Toshitaka Yajima, Nobuaki Sarai, Naoki Kashihara, Toshiki Nishio, Takeshi Osonoi, Yosuke Saka, Toshiyuki Imasawa, Takayasu Ohtake, Hiroshi Mizuno, Yugo Shibagaki, Hyosung Kim, Toshitaka Yajima, Nobuaki Sarai

Abstract

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.

Keywords: Hyperkalemia; Japan; Japanese; Sodium zirconium cyclosilicate.

Conflict of interest statement

N Kashihara has received consulting fees from AstraZeneca and has received research grants from AstraZeneca and the Japan Agency for Medical Research and Development. Y Saka, T Nishio, T Osonoi, T Imasawa, T Ohtake, H Mizuno, and Y Shibagaki have no conflicts of interest to disclose. H Kim, T Yajima, and N Sarai are employees of AstraZeneca K.K.

Figures

Fig. 1
Fig. 1
Study design. aPotassium concentrations measured before, and 1, 2, and 4 h after administration of the first dose. bPotassium concentrations measured before, and 1 and 4 h after the first dose. Randomization was stratified according to estimated glomerular filtration rate < 60 mL/min/1.73 m2 or ≥ 60 mL/min/1.73 m2. K+ potassium, R randomization, SZC sodium zirconium cyclosilicate, TID three times daily
Fig. 2
Fig. 2
Study flow diagram. Randomization was stratified according to estimated glomerular filtration rate 2 or ≥ 60 mL/min/1.73 m2. sK+ serum potassium, SZC sodium zirconium cyclosilicate
Fig. 3
Fig. 3
Proportion of normokalemic patients over time after administration of SZC (full analysis set). Normokalemia defined as sK+ 3.5–5.0 mmol/L. sK+ serum potassium, SZC sodium zirconium cyclosilicate
Fig. 4
Fig. 4
sK+ concentrations (mmol/L) over time after administration of SZC (mean ± SD) (full analysis set). The shaded area of the graph represents the range for normokalemia (sK+ 3.5–5.0 mmol/L). SD standard deviation, sK+ serum potassium, SZC sodium zirconium cyclosilicate

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