Efficacy and Safety of Sodium Zirconium Cyclosilicate for Treatment of Hyperkalemia: An 11-Month Open-Label Extension of HARMONIZE

Abstract

Background: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for treatment of hyperkalemia. An open-label extension (OLE) of the -HARMONIZE study evaluated efficacy and safety of SZC for ≤11 months.

Methods: Patients from HARMONIZE with point-of-care device i-STAT K+ 3.5-6.2 mmol/L received once-daily SZC 5-10 g for ≤337 days. End points included achievement of mean serum K+ ≤5.1 mmol/L (primary) or ≤5.5 mmol/L (secondary).

Results: Of 123 patients who entered the extension (mean serum K+ 4.8 mmol/L), 79 (64.2%) completed the study. The median daily dose of SZC was 10 g (range 2.5-15 g). The primary end point was achieved by 88.3% of patients, and 100% achieved the secondary end point. SZC was well tolerated with no new safety concerns.

Conclusion: In the HARMONIZE OLE, most patients maintained mean serum K+ within the normokalemic range for ≤11 months during ongoing SZC treatment.

Keywords: Extension; HARMONIZE; Hyperkalemia; Sodium zirconium cyclosilicate.

Fig. 1

Proportion of patients in the intent-to-treat population with mean serum K⁺ (a) ≤5.1 mmol/L and (b) ≤5.5 mmol/L with SZC by study visit and overall (days 8–337) in the maintenance phase. Error bars represent 95% CIs. Gray bar represents the proportion of patients across all visits in the maintenance phase. n, the number of patients meeting serum K⁺ threshold; N, the total number of evaluable patients; Min and Max, minimum and maximum serum K⁺ values, respectively, in mmol/L. K⁺, potassium.