Safety & Efficacy of Zirconium Silicate in Mild to Moderate Hyperkalemia
Condition: Hyperkalemia
MeSH terms: Hyperkalemia
Intervention: Zirconium silicate (acute phase); Zirconium silicate (subacute phase); Placebo (acute phase); Placebo ( subacute phase)
Intervention description: Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered 3 times (tid) daily with meals for 48 hours.; Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered once a day prior to the morning meal for 12 days.; Randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals for 48 hours during the acute phase.; Randomized to mimic doses of experimental drug administered once a day prior to the morning meal for 12 days during the subacute 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: 754.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Acute Phase: It is hypothesized that ZS (zirconium silicate) is more effective than placebo
      control (alternative hypothesis) in lowering S-K levels in subjects with S-K between 5.0 -
      6.5 mmol/l versus no difference between ZS and placebo control (null hypothesis).

      Subacute Phase (randomized withdrawal): It is hypothesized that ZS once daily is more
      effective than placebo control (alternative hypotheses) in maintaining normokalemic levels
      (3.5 - 4.9 mmol/l) among subjects completing the Acute Phase versus no difference between
      each ZS dose and respective placebo controls (null hypotheses).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of written informed consent.

          -  Over 18 years of age.

          -  Mean i-STAT potassium values between 5.0 - 6.5 mmol/l inclusive, at screening (Study
             Day 0).

          -  Ability to have repeated blood draws or effective venous catheterization.

          -  Women of childbearing potential must be practicing a highly effective method of birth
             control.

        Exclusion Criteria:

          -  Pseudohyperkalemia signs and symptoms, such as excessive fist clinching hemolyzed
             blood specimen, severe leukocytosis or thrombocytosis.

          -  Subjects treated with lactulose, xifaxan or other nonabsorbed antibiotics for
             hyperammonemia within the last 7 days.

          -  Subjects treated with resins (such as Sevelamer acetate or Sodium polystyrene
             sulfonate [SPS; e.g. Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum
             carbonate, within the last 7 days.

          -  Subjects with a life expectancy of less than 3 months.

          -  Subjects who are HIV positive.

          -  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 Ketoacidosis/Acidemia.

          -  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.

          -  Previous treatment with ZS

          -  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.

          -  Insulin-dependent diabetes mellitus

          -  Subjects on dialysis