Abstract: TH-PO1112

Maintained Efficacy and Safety of Sodium Zirconium Cyclosilicate for Hyperkalemia: 12-Month, Open-Label, Phase 3 Study

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 704 Fluid, Electrolyte, Acid-Base Disorders

Authors

  • Fishbane, Steven, Hofstra Northwell Health School of Medicine, Great Neck, New York, United States
  • 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
  • McCullough, Peter A., Baylor University Medical Center, Dallas, Texas, United States
  • Kosiborod, Mikhail, Saint Luke's Mid America Heart Institute, Kansas City, Missouri, United States
  • Pergola, Pablo E., Renal Associates PA , San Antonio, Texas, United States
  • Packham, David K., University of Melbourne, Melbourne, New South Wales, Australia
  • Roger, Simon D., Renal Research, Gosford, New South Wales, Australia
  • Lerma, Edgar V., UIC/ Advocate Christ, Oak Lawn, Illinois, United States
  • Butler, Javed, Stony Brook University, Stony Brook, New York, United States
  • Von haehling, Stephan, University of Göttingen Medical Centre, Göttingen, Germany
  • Spinowitz, Bruce S., New York-Presbyterian/Queens and Weill Medical College of Cornell University, Flushing, New York, United States
  • Block, Geoffrey A., Denver Nephrology, Denver, Colorado, United States
Background

We evaluated sodium zirconium cyclosilicate (ZS), an oral, highly selective potassium (K) binder for hyperkalemia over 12 mo.

Methods

This international, multicenter, open-label, single-arm phase 3 trial enrolled 751 outpatients (≥18y) with K≥5.1mEq/L. In acute phase (AP), patients (pts) received 10g ZS TID for 24–72h until K ≤5.0mEq/L by point-of-care device (iSTAT). 746 pts with K 3.5-5.0mEq/L by iSTAT entered an extended phase (EP) and received ZS titrated to K ≤5.0mEq/L (5g to start, min 5g every other day, max 15g daily) for ≤12mo without diet or RAASi restrictions. Primary endpoints were measured by central laboratory: % with normal K acutely; % with K≤5.1 or ≤5.5mEq/L during 3-12mo; mean K; adverse events (AE).

Results

Pts had a median age of 64y, 74% had eGFR <60, 38% had heart failure and 70% were on RAASi. During AP, baseline mean K decreased from 5.6 to 4.8 mEq/L; K 3.5-5.0mEq/L was achieved in 99% and 78% of pts when assessed by i-STAT and central lab, respectively; K 3.5-5.5mEq/L was achieved in 99% (central lab). Overall, 466 (62.5%) completed EP. Mean daily ZS dose was 7.2g. Normokalemia was maintained up to 12 mo [Figure]. During EP, mean K ≤5.1 or ≤5.5mEq/L was achieved in 88% and 99% of pts over 3-12 mo, respectively; 489 (65.5%) pts experienced an AE and 21.6% a serious AE. There were 8 (1.1%) deaths. Common AEs (>5%) were hypertension, peripheral edema, urinary tract infection, constipation, and anemia. Laboratory-determined hypokalemia (<3.5mEq/L) occurred in 5.8% (1.2% with K 2.5-<3.0).

Conclusion

ZS treatment rapidly reduced K in pts with hyperkalemia and maintained normokalemia for up to 12 mo; safety profile was consistent with prior studies and acceptable for this patient population.

Funding

  • Commercial Support