Clinical Trial: Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Multicenter, Multi-phase, Multi-dose, Prospective, Double-blind, Placebo-controlled, Maintenance Study of Safety and Efficacy of ZS (Microporous, Fractionated, Protonated Zirconium Silicate) in

Brief Summary: It is hypothesized that ZS is more effective than placebo control (alternative hypothesis) in maintaining mean double-blind randomized maintenance phase (DBRMP) Day 8-29 serum potassium levels (3.5 - 5.0 mmol/l, inclusive) among hyperkalemic subjects in whom normokalemia was established during the open-label acute phase versus no difference between each ZS dose (highest to lowest) versus placebo control (null hypothesis).

Detailed Summary:

Approximately 275 subjects with hyperkalemia (two consecutive i-STAT potassium levels ≥ 5.1 mmol/l, taken 60 minutes apart at baseline) will be enrolled in the Open-label Acute Phase to provide 232 subjects in the Double Blind Randomized Maintenance Phase.

Initially all subjects will receive open-label ZS at a dose of 10g three times a day (tid) for 48 hours (AP). Subjects who achieve normokalemia (i-STAT potassium values between 3.5 to 5.0 mmol/l, inclusive) on the morning of Study Day 3 (after 6 doses of 10g ZS) will then, in a double-blind fashion, be randomized 4:4:4:7 to receive one of three doses of ZS (5g, 10g or 15g) or placebo control, qd for the following 28 days (DBRMP).

Safety and tolerability will be assessed on an ongoing basis by an Independent Data Monitoring Committee (iDMC). Each active dose group in the DBRMP will consist of 49 subjects and the placebo control group will consist of 85 subjects for a total of 232 subjects to detect a 0.6 effect size difference between each ZS dose (from highest to lowest) and placebo control; the 4:4:4:7 allocation optimizes the multiple comparisons to the placebo control for the DBRMP.


Sponsor: ZS Pharma, Inc.

Current Primary Outcome: Maintenance of serum potassium level with once daily ZS for 28 days after establishment of normokalemia with ZS three times a day for first 48 hours. [ Time Frame: First 48 hours acute phase, then 28 days maintenance phase ]

To evaluate the safety and efficacy of three (3) different doses of ZS administered once daily (qd) for 28 days in maintaining normokalemia (serum potassium (S-K) between 3.5 - 5.0 mmol/l, inclusive) in subjects achieving normokalemia following two days of acute therapy for subjects with hyperkalemia (two consecutive i-STAT potassium values ≥ 5.1 mmol/l, taken 60 minutes apart) at baseline.


Original Primary Outcome: Same as current

Current Secondary Outcome: Proportion of subjects who convert from hyperkalemia to normokalemia after 10g ZS three times a day. [ Time Frame: First 48 hours ]

Evaluate the safety and efficacy of ZS in pre-defined subgroups of hyperkalemia including chronic kidney disease, diabetes mellitus, congestive heart failure, and patients taking Renin-Angiotensin-Aldosterone System (RAAS) inhibitors.


Original Secondary Outcome: Same as current

Information By: ZS Pharma, Inc.

Dates:
Date Received: March 12, 2014
Date Started: March 2014
Date Completion:
Last Updated: January 25, 2017
Last Verified: January 2017