Table 3.
Summary of sodium zirconium cyclosilicate (ZS9) clinical studies for the treatment of hyperkalemia
| Study design | Patient population | Primary end point(s) | Study treatment and duration | Major findings |
|---|---|---|---|---|
| Phase II, prospective, randomized, doubleyblind, placebo-controlled, dose-escalating clinical trial33 | Patients with stable stage 3 CKD (eGFR 30–59 mL/min/1.73 m2) and mild-to-moderate hyperkalemia (5–6 mEq/L) (n=90) | Rate of potassium concentration decline in the first 48 hours | ZS9 0.3 g, 3 g, or 10 g PO three times daily with meals or placebo for 48 hours (six doses) | Mean ± SD potassium-concentration reduction from baseline of –0.11±0.46 mEq/L at 1 hour with ZS9 10 g compared to an increase of 0.12±0.36mEq/L with placebo (P=0.04); reduction of –0.92±0.52 mEq/L with ZS9 10 g at 38 hours compared to –0.26±0.4 mEq/L with placebo (P<0.001) |
| Phase III, prospective, randomized, double-blind, placebo-controlled, two-stage, dose-ranging clinical trial18 | Initial phase: ambulatory outpatients with hyperkalemia (5–6.5 mEq/L) (n=754) | Initial phase: rate of change in mean potassium concentration compared to placebo over 48 hours | Initial phase: ZS9 1.25, 2.5 g, 5 g, or 10 g PO three times daily with meals or placebo for 48 hours | Initial phase: mean potassium-concentration reductions (per hour) of –0.16% for 2.5 g group, –0.21% for 5 g group, –0.30% for 10 g group, and –0.09% for placebo (P<0.001 for each comparison) |
| Maintenance phase: ambulatory outpatients with normal potassium (3.5–4.9 mEq/L) at hour 48 of the initial phase (n=543) | Maintenance phase: mean potassium concentration compared to placebo over 12 days | Maintenance phase: ZS9 dose from initial phase given once daily before breakfast or switched to placebo for days 3–14 | Maintenance phase: mean potassium concentration increases (per hour) of 0.14% for 10 g group vs 1.04% for placebo (P<0.001); increases of 0.09% for 5 g group vs 0.47% for placebo (P=0.008) | |
| HARMONIZE: Phase III, prospective, randomized, double-blind, placebo-controlled clinical trial25 | Open-label phase: ambulatory outpatients with hyperkalemia (≥5.1 mEq/L) (n=258) | Change in potassium concentration over 48 hours | Open-label phase: ZS9 10 g PO three times daily with meals for 2 days | Open-label phase: by 48 hours, the mean rate of potassium-concentration reduction (per hour) was –0.3% (95% CI –0.4% to –0.3%); the mean absolute reduction was 1.1 mEq/L (95% CI –1.1 to –1.0 mEq/L, P<0.001) |
| Randomized phase: ambulatory outpatients with normal potassium (3.5–5 mEq/L) at hour 48 of the initial phase (n=237) | Mean potassium concentration in each ZS9 group compared to placebo during days 8–29 of the randomized phase | Randomized phase: ZS9 5 g, 10 g, or 15 g PO once daily or placebo for 28 days | Randomized phase: mean potassium of 4.8 mEq/L (95% CI 4.6–4.9mEq/L) for 5 g group, 4.5 mEq/L (95% CI 4.4–4.6 mEq/L) for 10 g group, and 4.4 mEq/L (95% CI 4.3–4.5 mEq/L) for 15 g group compared to 5.1 mEq/L (95% CI 5–5.2 mEq/L) for placebo (P<0.001 for each comparison) |
Abbreviations: CI, confidence interval; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; PO, per os (by mouth); SD, standard deviation.