Effects of sodium zirconium cyclosilicate on sodium and potassium excretion in healthy adults: a Phase 1 study

Background. Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a potassium (K+) binder for treatment of hyperkalemia in adults. SZC binds K+ in exchange for sodium (Na+) or hydrogen (H+) in the gastrointestinal tract, conveying potential for systemic absorption of Na+. Methods. This single-center Phase 1 study evaluated the effects of SZC on Na+ and K+ excretion in healthy, normokalemic adults. During an initial run-in period (Days 1-2), participants started a high K+/low Na+ diet. After baseline (Days 3-4), SCZ 5 or 10 g once daily (QD) was administered (Days 5-8). The primary endpoint was mean change in urinary Na+ excretion from baseline (Days 3-4) to the treatment period (Days 7-8). Results. Of 32 enrolled participants, 30 entered and completed the study; the first 15 received 5 g and the next 15 received 10 g. Nonsignificant changes from baseline in urinary Na+ excretion were observed with SZC 5 g (mean +/- SD -0.93 +/- 25.85 mmol/24 h) and 10 g (-5.47 +/- 13.90 mmol/24 h). Statistically significant decreases from baseline in urinary K+ excretion (mean +/- SD -21.17 +/- 21.26 mmol/24 h; P = 0.0017) and serum K+ concentration (-0.25 +/- 0.24 mmol/L; P = 0.0014) were observed with the 10-g dose. There were few adverse events and no clinically meaningful changes in vital signs or laboratory safety measures. Conclusions. Treatment with SZC 5 or 10 g QD reduced serum K+ concentration and urinary K+ excretion, with no significant effect on urinary Na+ excretion, and was well tolerated.

Automated summary

The study suggests that sodium zirconium cyclosilicate can effectively reduce serum potassium concentration and urinary potassium excretion, with no significant impact on urinary sodium excretion, and is well tolerated.