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.