US-based pharmaceutical firm ZS Pharma has started patient enrolment in ZS004, its second randomised, double-blind, placebo-controlled Phase III clinical trial of ZS-9, a new investigational treatment for hyperkalemia.
The new trial is designed to confirm, over a longer treatment period, the positive results previously reported for ZS003, a Phase III trial involving a once-daily dose of ZS-9 (5g or 10g) maintaining potassium levels within the normal range with safety and tolerability similar to placebo.
Patients with hyperkalemia, including those with chronic kidney disease (CKD), heart failure, diabetes, and those on renin angiotensin aldosterone system (RAAS) inhibitor therapy are being enrolled in the global multicentre, multi-dose, prospective trial ‘ZS004’.
Around 275 patients with hyperkalemia will be given 10g of ZS-9 three times daily for 48 hours in the open-label induction phase of the trial.
The company said that patients who achieve normokalemia are eligible to be randomised in a double-blind fashion to one of three doses of ZS-9 (5g, 10g or 15g) or placebo administered once-daily for 28 days.
The ZS004 trial’s primary efficacy endpoint is the mean serum potassium level of each ZS-9 treatment group compared with that of placebo.
In addition to ZS004, the company will also carry out ZS004E, an extension study that will generate longer-term open-label safety, tolerability and efficacy data in patients who participated in ZS004.
In ZS004E, patients will be given an additional 60 days of treatment, resulting in a combined potential of 90 days of treatment with ZS-9 over the course of ZS004 and ZS004E.
The company recently completed a 753-patient Phase III trial, which showed that ZS-9 rapidly reduced serum potassium in hyperkalemic patients to normal levels within 48 hours and maintained potassium in the normal range with once-daily dosing.
In addition, the trial provided evidence that ZS-9 is safe and well-tolerated with an adverse event profile similar to placebo.
The company also intends to file a new drug application (NDA) with the US Food and Drug Administration (FDA) and a marketing authorisation application (MAA) with the European Medicines Agency (EMA) in the first half of 2015.
Image: Electrocardiography showing precordial leads in hyperkalemia. Photo: courtesy of Mikael Häggström.