Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.
Condition: Hyperkalemia
MeSH terms: Hyperkalemia
Intervention: Sodium zirconium cyclosilicate; Placebo
Intervention description: Sodium zirconium cyclosilicate; Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days (maintenance phase)
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 258.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of written informed consent.

          -  Over 18 years of age.

          -  Two consecutive i-STAT potassium values, measured 60-minutes apart, both ≥5.1 mmol/l
             and measured within 1 day of the first ZS dose on AP Study Day 1.

          -  Ability to have repeated blood draws or effective venous catheterization.

          -  Women of childbearing potential must be using two forms of medically acceptable
             contraception (at least one barrier method) and have a negative pregnancy test at AP
             Study Day 1. Women who are surgically sterile or those who are post-menopausal for at
             least 2 years are not considered to be of childbearing potential.

        Exclusion Criteria:

          -  Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed
             blood specimen, history of severe leukocytosis or thrombocytosis.

          -  Subjects treated with lactulose, Xifaxan or other non-absorbed antibiotics for
             hyperammonemia within 7 days prior to the first dose of study drug.

          -  Subjects treated with resins (such as sevelamer acetate or sodium polystyrene
             sulfonate [SPS; e.g. Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum
             carbonate, within 7 days prior to the first dose of study drug.

          -  Subjects with a life expectancy of less than 3 months.

          -  Subjects who are severely physically or mentally incapacitated and who in the opinion
             of investigator are unable to perform the subjects' tasks associated with the
             protocol.

          -  Women who are pregnant, lactating, or planning to become pregnant.

          -  Subjects with diabetic ketoacidosis.

          -  Presence of any condition which, in the opinion of the investigator, places the
             subject at undue risk or potentially jeopardizes the quality of the data to be
             generated.

          -  Known hypersensitivity or previous anaphylaxis to ZS or to components thereof.

          -  Randomization into the previous ZS-002 or ZS-003 studies.

          -  Treatment with a drug or device within the last 30 days that has not received
             regulatory approval at the time of study entry.

          -  Subjects with cardiac arrhythmias that require immediate treatment.

          -  Subjects on dialysis.