The results of the ZS-9 Phase 3 clinical trial has been announced by specialty pharmaceutical company ZS Pharma. The novel therapeutic drug was investigated to study the acute phase response in the management of hyperkalemia, a life threatening complication of various systemic health issues.
ZS-003 Phase 3 Trial:
The specialty pharmaceutical company reported the successful completion of the Acute Phase of ZS-003 and release of preliminary data at the primary end-points. Towards the end of the initial 48 hours, all patients reported a significant reduction in the serum concentration of potassium (K+).
These results are in line with prior positive data obtained at the end of a double-blind, placebo-controlled study of ZS-002 (Phase 2 trial). The primary end-point of these two studies indicate high efficacy and safety of the novel drug in the management of hyperkalemia.
The results were presented in ASN’s Kidney Week 2013 during the High-Impact Clinical Trials Oral Session by Indiana University Health Arnett researcher, Dr. Stephen R. Ash (as reported by the Fort Mill Times). Dr Ash said:
“Hyperkalemia is a serious medical condition associated with significantly increased mortality rates, but physicians lack a safe and reliable therapy to lower serum K+ levels. ZS-9 shows promise as an effective, well tolerated, fast-acting, and predictable treatment for patients with hyperkalemia.”
Details of the Phase 3 results:
A total of 753 patients were enrolled in the multi-center, double-blind, placebo-controlled randomized ZS-003 study. All study participants had moderate to severe hyperkalemia (with serum potassium concentration in the range of 5-6.5 mEq/L). Other inclusion criteria included, co-morbid medical conditions like heart failure, diabetes, chronic kidney disease (CKD), or current medical therapy with renin angiotensin aldosterone system (RAAS) inhibitor therapy.
All patients were randomly assigned to receive either of the four doses (1.25g, 2.5g, 5g or 10g) of investigational drug ZS-9 or a placebo. During the Acute phase, 3 doses of the drug were given daily for the initial 48 hours, and rate of change of serum potassium concentration was observed. Normalized patients were then prescribed the active drug in a dose of (1.25g, 2.5g, 5g or 10g) by random selection or placebo administration once a day for 12 days (during the sub-acute phase of trial). The rate of change in the serum concentration of potassium over the course of the 12-day therapy was set as the secondary end-point.
Significantly positive results were reported at doses 2.5g, 5g, and 10g compared to the placebo.
The average rate of reduction in the serum K+ concentration at the dose of 10g was -0.73 mEq/L , 14 hours after the last dose at the end of acute phase (or completion of 48 hours)
The drug was also well-tolerated with minimal rate of side-effects, mostly gastrointestinal (that were also reported in the placebo group). The data of Sub-Acute phase is expected in the coming months and is hoped to simulate the Acute Phase results.
Director of clinical research at Denver Nephrology and an investigator in Zs-003 study, Dr. Geoff Block commented:
“The preliminary Phase 3 study results are promising and I look forward to additional Phase 3 results as they become available. There is a critical need for a new treatment for patients with hyperkalemia, including those with chronic kidney disease, diabetes, heart failure and those who should be on cardio-renal protective treatment such as ACEs and ARBs.”
Dr. Block is also an associate clinical professor of medicine at the University of Colorado Health Sciences Center.
Phase 2 Trial Design and Results
90 patients were enrolled in the Phase 2 Trial (Zs-002) for the management of hyperkalemia (5-6 mEq/L) in the setting of Stage -3 chronic kidney disease (CKD). The study group was assigned in 4 different groups (placebo group with 30 patients and treatment group with a:
– Dose of 0.3g (3 times daily) in 12 patients.
– Dose of 0.3g (3 times daily) in 24 patients.
– Dose of 10g (3 times daily) in 24 patients.
Rate of change of serum potassium concentration was observed in 48 hours. The results obtained indicated efficacy and maximum effectiveness at 5g and 10g dosages. Salient features of the report include:
– At the end of the Acute Phase, 63% patients reported greater than 1.0 mEq/L decline in serum potassium concentration as opposed to only 17% in the placebo group.
– No adverse effects or side effects reported (suggesting excellent tolerance of the drug).
– A comparative analysis in patients with (RAAS) inhibitor therapies suggested improvement in the serum potassium concentration that was consistent with the other study participants.
– The positive effects of therapy in reducing the serum concentration lasts fairly long (even after hours of last dosage).
About the ZS-9 Clinical Development Program:
The aim of this clinical trial is to identify a safe and effective therapeutic dosage for the lead product candidate ZS 9. The company is also planning to initiate another trial in early 2014 as ZS-004 to assess the efficacy in long term therapy (for a period of 1- month).
About ZS Pharma:
The Coppell, Texas-based specialty pharmaceutical company aims at devising and developing novel therapeutic regimens for the management of chronic metabolic issues like hyperkalemia. Additionally, the company is also developing an additional drug by utilizing selective ion-trap technology.