US-based pharmaceutical firm ZS Pharma has completed patient enrolment in its Phase III clinical trial (ZS-003) evaluating the ability of ZS-9 for the treatment of hyperkalemia, a life-threatening condition.
Hyperkalemia is differentiated by higher than normal levels of potassium (K+) in the blood serum and its basic causes include chronic kidney disease, heart failure, diabetes and cardio-renal protective RAAS inhibitor therapies, like ACEs, ARBs and aldosterone blockers.
ZS-9 is orally administered as a tasteless, odourless powder or tablet. It uses a novel selective ion-trap technology to preferentially capture and eliminate excess potassium.
The randomised, double-blind, Phase III clinical trial of ZS-9 called ZS-003, which is designed to investigate treatment of acute, subacute and chronic hyperkalemia, also had a 12-day sub-acute phase to explore extended dosing of ZS-9.
The ZS-003 trial is aimed at showing the rapid, safe and effective reduction of potassium in hyperkalemic patients within 48 hours.
Around 750 patients with hyperkalemia (potassium levels 5-6.5 mEq/L), including patients with chronic kidney disease, heart failure, diabetes and those on RAAS inhibitor therapy were enrolled in the trial.
In the acute phase of the study, patients were given one of four doses of ZS-9 (1.25g, 2.5g, 5g or 10g) or placebo, administered three times daily for the initial 48 hours.
The acute phase was followed by a subacute phase, in which normalised patients received once-daily doses of ZS-9 (1.25g, 2.5g, 5g or 10g) or placebo for 12 days.
In the acute phase, the primary endpoint of the trial was the rate of change in serum potassium from baseline to day two, while for the subacute phase, the primary endpoint was the rate of change in serum potassium from study day three (baseline of the Subacute Phase) through the following 12 days.
ZS Pharma executive chairman Robert Alexander said: "With enrolment in our Phase III trial now complete, we are in a position to have top-line results by year end and to advance the clinical development of ZS-9."
The company also intends to start an additional month-long, randomised, double-blind, placebo-controlled Phase III trial called ZS-004, in early 2014 in order to confirm the optimal dose for extended treatment.
In addition, the company is also engaged in the discovery of new drug candidates that utilise its novel selective ion-trap technology for the treatment of kidney and liver diseases.
ZS-9 is currently being tested in approximately 1,500 hyperkalemic patients with underlying chronic kidney disease, diabetes, congestive heart failure, and in those patients on cardio-renal protective RAASi therapy.
The company believes that ZS-9 through its successful combination of high-capacity, selectivity, and unique structure can effectively, safely, and rapidly remove excess potassium and maintain normal potassium levels with a relatively low drug burden.