NCT02088073

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

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 258 (actual)
• Sponsor: ZS Pharma, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 description

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.

Conditions

• Hyperkalemia

Interventions

Type	Name	Description
DRUG	Sodium zirconium cyclosilicate	Sodium zirconium cyclosilicate
DRUG	Placebo	Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days (maintenance phase)

Timeline

• Start date: 2014-03-31
• Primary completion: 2014-08-31
• Completion: 2015-01-31
• First posted: 2014-03-14
• Last updated: 2018-12-07
• Results posted: 2018-12-07

Locations

46 sites across 3 countries: United States, Australia, South Africa