Abstract
BackgroundSodium zirconium cyclosilicate (SZC) is an oral potassium binder approved to treat hyperkalemia in adults in a number of countries, including Japan.MethodsThis phase 2/3, randomized, double-blind, placebo-controlled, dose–response study (ClinicalTrials.gov: NCT03127644) was designed to determine the efficacy and safety of SZC in Japanese adults with hyperkalemia. Patients with serum potassium (sK+) concentrations ≥ 5.1– ≤ 6.5 mmol/L were randomized 1:1:1 to SZC 5 g, SZC 10 g, or placebo three times daily for 48 h (six doses total). The primary efficacy endpoint was the exponential rate of change in sK+ over 48 h. The proportion of patients with normokalemia (sK+ 3.5–5.0 mmol/L) at 48 h and adverse events (AEs) were also evaluated.ResultsOverall, 103 patients (mean age, 73.2 years; range 50–89 years) received SZC 5 g (n = 34), SZC 10 g (n = 36), or placebo (n = 33). The exponential rate of sK+ change from 0 to 48 h versus placebo was − 0.00261 (SZC 5 g) and – 0.00496 (SZC 10 g; both P < 0.0001). At 48 h, the proportions of patients with normokalemia were 85.3%, 91.7%, and 15.2% with SZC 5 g, SZC 10 g, and placebo, respectively. No serious AEs were reported. Hypokalemia (sK+ < 3.5 mmol/L) occurred in two patients in the SZC 10 g group; normokalemia was re-established within 6 days and no treatment-related AEs were reported.ConclusionSZC is effective and well tolerated in Japanese patients with hyperkalemia.
Highlights
Hyperkalemia, a common electrolyte disorder defined by elevated serum potassium (sK+), is often associated with comorbidities such as chronic kidney disease (CKD), heart failure (HF), and diabetes [1]
Our study met its primary efficacy endpoint; both Sodium zirconium cyclosilicate (SZC) 5 g and 10 g resulted in significantly greater exponential decreases in sK+ concentration from baseline at 48 h versus placebo
The exponential rate of change was selected as a more clinically relevant endpoint than absolute change from baseline, since it incorporates the time to onset of effect and all sK+ measurements throughout the 48 h
Summary
Hyperkalemia, a common electrolyte disorder defined by elevated serum potassium (sK+), is often associated with comorbidities such as chronic kidney disease (CKD), heart failure (HF), and diabetes [1]. In Japan, the overall prevalence of hyperkalemia in a hospital claims database population was 67.9 patients per 1000; this increased to 227.9, 134.0, 108.4, and 142.2 patients per 1000 in those with CKD, HF, diabetes, and RAASi therapy, respectively [1]. Methods This phase 2/3, randomized, double-blind, placebo-controlled, dose–response study (ClinicalTrials.gov: NCT03127644) was designed to determine the efficacy and safety of SZC in Japanese adults with hyperkalemia. Patients with serum potassium (sK+) concentrations ≥ 5.1– ≤ 6.5 mmol/L were randomized 1:1:1 to SZC 5 g, SZC 10 g, or placebo three times daily for 48 h (six doses total). Hypokalemia (sK+ < 3.5 mmol/L) occurred in two patients in the SZC 10 g group; normokalemia was re-established within 6 days and no treatment-related AEs were reported. Conclusion SZC is effective and well tolerated in Japanese patients with hyperkalemia
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