Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level ≥ 5.5 mmol/L: pooled analysis from two phase 3 trials

Alpesh N Amin, Jose Menoyo, Bhupinder Singh, Christopher S Kim, Alpesh N Amin, Jose Menoyo, Bhupinder Singh, Christopher S Kim

Abstract

Background: Reliable, timely-onset, oral treatments with an acceptable safety profile for patients with hyperkalemia are needed. We examined the efficacy and safety of sodium zirconium cyclosilicate (SZC; formerly ZS-9) treatment for ≤ 48 h in patients with baseline serum potassium level ≥ 5.5 mmol/L.

Methods: Data were pooled from two phase 3 studies (ZS-003 and HARMONIZE) among patients receiving SZC 10 g three times daily. Outcomes included mean and absolute change from baseline, median time to potassium level ≤ 5.5 and ≤ 5.0 mmol/L, and proportion achieving potassium level ≤ 5.5 and ≤ 5.0 mmol/L at 4, 24, and 48 h. Outcomes were stratified by baseline potassium. Safety outcomes were evaluated.

Results: At baseline, 125 of 170 patients (73.5%) had potassium level 5.5-< 6.0, 39 (22.9%) had potassium level 6.0-6.5, and 6 (3.5%) had potassium level > 6.5 mmol/L. Regardless of baseline potassium, mean potassium decreased at 1 h post-initial dose. By 4 and 48 h, 37.5% and 85.0% of patients achieved potassium level ≤ 5.0 mmol/L, respectively. Median (95% confidence interval) times to potassium level ≤ 5.5 and ≤ 5.0 mmol/L were 2.0 (1.1-2.0) and 21.6 (4.1-22.4) h, respectively. Fifteen patients (8.8%) experienced adverse events; none were serious.

Conclusions: SZC 10 g three times daily achieved serum potassium reduction and normokalemia, with a favorable safety profile.

Trial registration: ClinicalTrials.gov identifiers: ZS-003: NCT01737697 and HARMONIZE: NCT02088073.

Keywords: Efficacy; Hyperkalemia; Safety; Sodium zirconium cyclosilicate.

Conflict of interest statement

AA has served on advisory panels for ZS Pharma Inc., a member of the AstraZeneca Group. JM and BS were employees of ZS Pharma, Inc., a member of the AstraZeneca Group, at the time of the analysis and own stock in AstraZeneca. CSK has served on advisory panels for ZS Pharma, Inc., a member of the AstraZeneca Group, and has served on panels for Actavis Pharma, Inc.

Figures

Fig. 1
Fig. 1
Mean (95% CI) serum K+ over time. CI, confidence interval; K+, potassium. *p ≤ 0.001; †p < 0.01; ‡p < 0.05 for absolute change from baseline
Fig. 2
Fig. 2
Patients with serum potassium (K+) levels (a) ≤ 5.5 mmol/L and (b) ≤ 5.0 mmol/L at various time points

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