An Evaluation of the Pharmacodynamics, Safety, and Tolerability of the Potassium Binder RDX7675.

Abstract

Hyperkalemia is common in patients with heart failure or chronic kidney disease, particularly those taking renin-angiotensin-aldosterone system inhibitors, and can cause arrhythmias and sudden cardiac death. The most widely used treatment, sodium polystyrene sulfonate (SPS), limits gastrointestinal potassium absorption, but has poor palatability. RDX7675 (RDX227675) is the calcium salt of a reengineered polystyrene sulfonate-based resin with improved palatability over SPS. The pharmacodynamic effects and safety of RDX7675 were assessed in a phase 1, single-center, randomized, active-controlled study. Healthy volunteers received nominal active doses of RDX7675 4.6g twice a day (BID), 4.6g 3 times a day (TID), 6.9g BID, 13.7g daily (QD), 9.2g TID, or 13.7g BID (n=12 each), or equivalent doses of SPS (n=3 each), for 4days. RDX7675 dosing increased stool potassium excretion and decreased urinary potassium excretion from baseline. Stool potassium excretion increased by up to 1481mg/day with RDX7675 (6.9g BID), and urinary potassium excretion decreased by up to 939mg/day (13.7gBID). Similar levels of potassium excretion were observed using QD, BID, or TID dosing of a 13.7g total daily RDX7675 dose. Few adverse events were reported. In conclusion, repeated oral dosing with RDX7675 over 4days reduced potassium absorption in healthy volunteers; the results support QD dosing of RDX7675 in future clinical studies.