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

Abstract

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.

Keywords: Phase 1 study; excretion; hyperkalemia; potassium; sodium; sodium zirconium cyclosilicate.

FIGURE 1:

Study design. ^aParticipants began a standardized diet of 920 mg or 40 mmol (±10%) Na⁺ and 5005 mg or 128 mmol (±10%) K⁺ per day (continued until study Day 9). ^bSZC was administered to two dose groups (5 or 10 g QD). ^cParticipants discharged from clinic at study Day 9. ^dDefined as nothing by mouth except water for ≥8 h prior to collection of any sample.

FIGURE 2:

Study participant disposition. The broken line indicates sequential SZC administration in the two dose groups (the SZC 5 g group was evaluated first, followed by the SZC 10 g group).

FIGURE 3:

Mean change from baseline (Days 3–4) to treatment period (Days 7–8) in (A) urinary sodium excretion, (B) urinary potassium excretion, (C) fecal sodium excretion and (D) fecal potassium excretion with SZC 5 or 10 g QD. Error bars are the SD. Circles and squares show values for individual participants in the SZC 5 g and SZC 10 g groups, respectively. *P < 0.01 versus baseline. **P < 0.05 versus baseline.

FIGURE 4:

Mean change from baseline (Days 3–4) to treatment period (Days 7–8) in serum potassium concentration with SZC 5 or 10 g QD. Error bars are the SD. Circles and squares show values for individual participants in the SZC 5 g and SZC 10 g groups, respectively. *P < 0.01 versus baseline.

FIGURE 5:

Mean daily fecal excretion of (A) sodium and (B) potassium on study Days 3 and 4 (baseline) and study Days 7 and 8 (treatment period). Error bars are the SD. Circles and squares show values for individual participants in the SZC 5 g and SZC 10 g groups, respectively.