Abstract 14911: RDX227675, the Calcium Salt of a Novel Polystyrene Sulfonate-Based Resin, Reduces Potassium Absorption in Healthy Volunteers
Introduction: Patients with heart failure or chronic kidney disease, especially those taking RAAS inhibitors, are at high risk of developing hyperkalemia, which can lead to consequences such as sudden cardiac death. Poor palatability of sodium polystyrene sulfonate (SPS), a current treatment, limits its use in these patients. RDX227675, the calcium salt of a polystyrene sulfonate-based resin, is a potassium (K) binder designed to have improved palatability being developed as a novel treatment for hyperkalemia. We investigated the ability of various dosing regimens of RDX227675 to reduce K absorption in healthy volunteers.
Methods: In this phase 1, single-center, active-controlled, randomized study, six cohorts of 15 healthy men and women received either RDX227675 (n = 12) at doses of 4.5 g tid, 9.0 g tid, 6.8 g bid, 4.5 g bid, 13.5 g qd, or 13.5 g bid, or the corresponding doses of SPS (Resonium A®; n = 3), for 4 days. Volunteers received a diet standardized for K content for 6 days, including a 2-day treatment-free baseline period. Stool and urine samples were collected to assess 24-h electrolyte excretion (urine, K only).
Results: RDX227675 was generally well tolerated at all doses. RDX227675 and SPS treatment resulted in increases in stool K over the treatment period, with concomitant reductions in urinary K. Mean increases in stool K from baseline were as high as ~1500 mg/day, with decreases in urinary K of up to ~900 mg/day in the RDX227675 groups, with similar magnitudes in the SPS groups. Similar levels of K excretion were observed using qd, bid, and tid dosing of the same 13.5 g total daily RDX227675 dose (Figure). Volunteers taking RDX227675 had increased stool sodium and calcium excretion with little or no change in stool magnesium or phosphorus excretion.
Conclusions: RDX227675 treatment over 4 days reduced absorption of K in healthy volunteers, as shown by increases in stool K with concomitant reductions in urinary K. Results support qd dosing in future clinical studies.
Author Disclosures: V. Zann: Employment; Significant; Quotient Clinical. C. Roe: Employment; Significant; Quotient Clinical. J.W. Jacobs: Employment; Significant; Ardelyx. Ownership Interest; Significant; Ardelyx. J.P. Davidson: Employment; Significant; Ardelyx. Ownership Interest; Significant; Ardelyx. R.C. Blanks: Employment; Significant; Ardelyx. Ownership Interest; Significant; Ardelyx. D.P. Rosenbaum: Employment; Significant; Ardelyx. Ownership Interest; Significant; Ardelyx.
- © 2016 by American Heart Association, Inc.