Safety & Efficacy of Zirconium Silicate in Chronic Kidney Disease or Moderate Kidney Dysfunction With Mild Hyperkalemia
Condition: Hyperkalemia; Chronic Kidney Disease; Kidney Dysfunction
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Hyperkalemia
Intervention: Zirconium silicate (ZS); Placebo
Intervention description: Randomized escalating doses (0.3g, 3g and 10g) of ZS (fractionated, protonated microporous Zirconium Silicate, an oral sorbent) administered 3 times daily (tid) with meals.; Randomized to mimic escalating doses of experimental drug administered 3 times daily (tid) with meals.
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of written informed consent.

          -  Over 18 years of age.

          -  GFR between 40-60 ml/min as estimated by the CKD-EPI equation. After screening two
             additional GFR values of between 40-60ml/min must be repeated within 24 hours before
             inclusion is allowed.

          -  S-K between 5.0 - 6.0 mmol/l (inclusive) during Study Day 0.

          -  Ability to have repeated blood draws or effective venous catheterization.

          -  Women of child bearing potential must be practicing a highly effective method of birth
             control.

        Exclusion Criteria:

          -  Pseudohyperkalemia such as excessive fist clinching hemolyzed blood specimen, severe
             leukocytosis or thrombocytosis.

          -  Subjects treated with lactulose, xifaxan or other non-absorbed antibiotics for
             hyperammonemia within the last 7 days.

          -  Subjects treated with resins (such as sevelamer acetate, calcium acetate or calcium
             carbonate, lanthanum carbonate, Sodium polystyrene sulfonate (SPS; e.g. Kayexalate®)
             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.

          -  Cancer within the last 5 years (other than successfully treated basal or squamous cell
             carcinoma of the skin, carcinoma in situ of the cervix or early stage prostate
             cancer).

          -  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 Zirconium Silicate or to components
             thereof.

          -  Subjects who have cardiac arrhythmias that require immediate treatment.

          -  Subjects with ECG changes associated with hyperkalemia.

          -  Subjects with acute kidney injury.