ZS-9 Leads to Decrease in Serum Potassium in CKD Patients with Hyperkalemia

New York—Hyperkalemia is a condition caused by abnormally high levels of potassium in the blood. It is associated with significant mortality and limits the use of lifesaving renin-angiotensin-aldosterone system (RAAS) inhibitors, yet current therapies are limited. ZS-9 is an insoluble, nonsystematically absorbed cation exchanger specifically designed to entrap excess potassium in the gastrointestinal tract. In a phase 2 trial involving chronic kidney disease (CKD) patients with hyperkalemia, 10 g ZS-9 led to a rapid and sustained decrease in serum potassium, with a favorable safety profile.

During a poster session at the ASH meeting, several posters were presented on this topic. B. Singh and colleagues presented 2 studies that evaluated ZS-9 for the treatment of hyperkalemia in patients with CKD. For both studies, patients were randomized to receive oral ZS-9 (0.3 g [n=12], 3 g [n=24], 10 g [n=24]) or placebo (n=30) 3 times a day for 2 days with regular meals as inpatients. In the first poster, titled Effect of ZS-9, a Novel Selective Cation Trap, on Urinary Potassium and Sodium Excretion When Used for the Treatment of Hyperkalemia in Patients with Chronic Kidney Disease, the researchers compared 24-hour sodium and potassium excretion in patients treated with 10 g ZS-9 versus placebo. Twenty-four hour urine samples were collected at baseline and during treatment. Patients were able to continue use of RAAS inhibitors.

ZS-9 demonstrated dose-dependent reductions in serum potassium; the primary end point was met in the 3 g and 10 g ZS-9 dose groups (P=.048 and P<.0001 vs placebo, respectively). Furthermore, 24-hour urine potassium excretion was significantly lower in the 10 g ZS-9 group than in the placebo group on days 1 and 2; at 48 hours, urinary potassium excretion increased by 31% with placebo and decreased by 23% with 10 g ZS-9, according to the study’s results.

In the second poster presented by B. Singh and colleagues, titled Change from Baseline in Serum K+ with ZS-9 in Patients with Chronic Kidney Disease Treated for Hyperkalemia, researchers assessed the change in serum potassium from baseline and the rate-of-change during the initial 48 hours of treatment with 10 g ZS-9 versus placebo. Serum potassium was measured at 0.5, 1, 2, and 4 hours after the initial dose on day 1 and every 4 hours post-dose thereafter. Rate of decline in serum potassium for 10 g ZS-9 were averaged over 2 on-drug daytime treatment periods (hours 0-14 and 24-38) and 2 off-drug nighttime rebound periods (hours 14-24 and 38-48). In the placebo and 10 g ZS-9 groups, 63% and 46%, respectively, of patients had a history of diabetes and 60% and 83%, respectively, were receiving RAAS inhibitor therapy at study entry, which was continued unchanged during the trial. At baseline, mean serum potassium was 5.1 mEq/L for placebo and 10 g ZS-9 groups in the overall population.

The results showed serum potassium reduction with 10 g ZS-9 differed significantly from placebo as early as 1 hour after the first dose (-0.11 vs +0.12 mEq/L; P<.05) and between 28 to 48 hours (P≤.001). The maximal absolute change in serum potassium (-1.1 mEq/L) occurred at 38 hours, 4 hours after the last dose. Additionally, there was a greater mean daytime rate of decline in serum potassium for 10 g ZS-9 versus placebo, overall (0.53 mEq/L/14-hour, P=.001).

As for adverse events, the researchers noted that ZS-9 was well-tolerated in both studies; ≥1 treatment-emergent adverse events occurred in 3 (10%) placebo patients and in 12 (20%) ZS-9-treated patients.—Eileen Koutnik-Fotopoulos

The studies were supported by ZS Pharma Inc.