Clinical Trial: Safety & Efficacy of Zirconium Silicate in Chronic Kidney Disease or Moderate Kidney Dysfunction With Mild Hyperkalemia

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

Official Title: Multicenter, Prospective, Randomized, Placebo-Controlled, Double-blind Dose Escalating Study of Safety, Tolerability and Pharmacodynamics of Zirconium Silicate in Chronic Kidney Disease and Moderate K

Brief Summary: It is hypothesized that zirconium silicate is safe and well tolerated and more effective than placebo (alternative hypothesis) in lowering serum potassium levels in subjects with serum potassium between 5 - 6.0 mmol/l versus no difference between zirconium silicate and placebo (null hypothesis). It is hypothesized that zirconium silicate even up to the top dose of 10g three times a day is well tolerated.

Detailed Summary:

A total of 90 subjects with moderate CKD (defined as GFR between 40- 60ml/min) and mild hyperkalemia (S-K between 5-6 mmol/l) will be enrolled in the study where, in a double-blind dose-escalating fashion (three separate cohorts), they will be randomized to receive one of the doses of ZS (0.3g, 3g and 10g) or placebo, administered 3 times (tid) daily with meals. The first cohort will have 18 subjects while both of the second and third cohorts will have 36 subjects for a total of 90 subjects.

Safety and tolerability will be assessed by an Independent Data Safety Monitoring Board (DSMB) after completion of each cohort, before escalation to the next dose level will be allowed. The next dose escalation will happen no sooner than one week after the last dose of study drug at the previous dosing level has been administered. Safety stopping rules will be specified for this study. Within the first dose level (300 mg dose), 12 subjects will be randomized to receive ZS, whereas 6 subjects will be randomized to receive placebo for a total of 18 subjects in this first cohort. In the next two cohorts (3 g and 10 g doses), 24 subjects per cohort will be randomized to receive ZS, whereas 12 subjects per cohort will be randomized to receive placebo for a total of 36 subjects in each of the second and third cohorts.


Sponsor: ZS Pharma, Inc.

Current Primary Outcome: Change in serum potassium levels from baseline after administration of zirconium silicate three times a day. [ Time Frame: during the first 48 hours ]

To evaluate the effect on serum potassium (S-K)) of 3 different doses of zirconium silicate (ZS) administered 3 times daily for 48 hours (with up to an additional 48 hours of three times a day dosing for subjects whose S-K has not normalized [3.5 - 4.9 mmol/l] after the initial 48 hours) to subjects with moderate Chronic Kidney Disease (CKD as defined by a glomerular filtration rate (GFR) between 40-60ml/min) and mild hyperkalemia (S-K between 5-6.0 mmol/l).


Original Primary Outcome: Same as current

Current Secondary Outcome: Identify optimal zirconium silicate dose to normalize serum potassium levels between 3.5 - 4.9 mmol/L without causing serious adverse events [ Time Frame: 6 months ]

Original Secondary Outcome: Same as current

Information By: ZS Pharma, Inc.

Dates:
Date Received: December 12, 2011
Date Started: November 2011
Date Completion:
Last Updated: June 2, 2016
Last Verified: June 2016