Abstract: FR-PO1074

Efficacy and Safety of Short-Term Treatment with Sodium Zirconium Cyclosilicate (ZS-9) for Hyperkalemia: Open-Label, Phase 3 Trial

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 704 Fluid, Electrolyte, Acid-Base Disorders

Authors

  • Packham, David K., U. of Melbourne, Melbourne, New South Wales, Australia
  • McCullough, Peter A., Baylor U. Medical Center, Dallas, Texas, United States
  • Kosiborod, Mikhail, Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, United States
  • Spinowitz, Bruce S., New York Presbyterian Queens, New York, New York, United States
  • Fishbane, Steven, Hofstra Northwell Health School of Med., Great Neck, New York, United States
  • Pergola, Pablo E., Renal Associates PA, San Antonio, Texas, United States
  • Lerma, Edgar V., UIC/ Advocate Christ, Oak Lawn, Illinois, United States
  • Butler, Javed, Stony Brook U., Stony Brook, New York, United States
  • Von haehling, Stephan, U. of Göttingen Medical Centre, Göttingen, Germany
  • Adler, Scott H., AstraZeneca, Gaithersburg, Maryland, United States
  • Singh, Bhupinder, ZS Pharma Inc., part of AstraZeneca, San Mateo, California, United States
  • Lavin, Philip T., Boston Biostatistics Research Foundation, Framingham, Massachusetts, United States
Background

Correction of hyperkalemia (HK) is important for the clinical management of patients (pts). Sodium zirconium cyclosilicate (ZS-9) is a selective, inorganic, potassium (K)-binder. We report results of ≤72h of ZS-9 treatment from the largest study of treated HK pts to date.

Methods

This international, open-label, single-arm trial with no dietary K or RAASi restrictions enrolled 751 outpatients (≥18y) with HK (K≥5.1mmol/L). Pts received 10g ZS-9 TID for 24–72h until normokalemic (K3.5–5.0 mmol/L; blood K measured by point-of-care device [iSTAT]). Treatment decisions were based on iSTAT K, generally considered to be highly accurate; efficacy endpoints were based on serum K from central lab per usual practice. Endpoints were achievement of normokalemia, overall response rate (%), change in K from baseline (ΔK), and adverse events (AE).

Results

99.3% of pts completed. By 24h, ΔK was -0.8 mmol/L (iSTAT, -14.9%; from 5.5 to 4.7 mmol/L) and -0.7 mmol/L (serum, -12.7%; from 5.6 to 4.9 mmol/L). Overall, 99.5% (95% CI [99%, 100%]) of pts achieved normokalemia by iSTAT and 77.9% (95% CI [75%, 81%]) by serum K. 100% of pts experienced a reduction in K (regardless of measurement method) with 92% having K reductions ≥0.5 mmol/L; 0.4% of pts had iSTAT K>5.0mmol/L and 22% had serum K>5.0mmol/L (Figure). 4.1% of pts experienced an AE. Most common were nausea (0.5%) and urinary tract infection (UTI; 0.5%); 1 pt each had peripheral edema and serum K3.0-<3.5mmol/L. UTI was the 1 SAE (resulting in the only hospitalization), and 2 pts discontinued due to AEs (UTI, flatulence, and upper abdominal pain). No deaths occurred.

Conclusion

ZS-9 rapidly and reliably normalized K in nearly all HK pts, with a safety profile similar to prior studies.

Funding

  • Commercial Support