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

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.

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

Study flow diagram. Randomization was stratified according to estimated glomerular filtration rate < 60 mL/min/1.73 m² or ≥ 60 mL/min/1.73 m². sK⁺ serum potassium, SZC sodium zirconium cyclosilicate

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

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