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.