A Study to Test Whether ZS (Sodium Zirconium Cyclosilicate) Can Reduce the Incidence of Increased Blood Potassium Levels Among Dialized Patients.
Condition: Hyperkalemia
MeSH terms: Hyperkalemia
Intervention: Placebo; Sodium Zirconium Cyclosilicate (ZS)
Intervention description: Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) .
Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.; Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) .
Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 196.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy of ZS in the treatment of hyperkalemia
      in patients on hemodialysis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of informed consent prior to any study specific procedures

          2. Female or male aged ≥ 18 years at screening Visit 1. For patients aged <20 years and
             enrolled in Japan, a written informed consent should be obtained from the patient and
             his or her legally acceptable representative.

          3. Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of endstage
             renal disease (ESRD) for at least 3 months before randomization.

          4. Patients must have hemodialysis access consisting of an arteriovenous fistula, AV
             graft, or tunneled (permanent) catheter which is expected to remain in place for the
             entire duration of the study.

          5. Pre-dialysis serum K >5.4 mmol/L after long inter-dialytic interval and >5.0 mmol/L
             after one short inter-dialytic interval during screening (as assessed by central lab).

          6. Prescribed dialysate K concentration ≤ 3 mmol/L during screening

          7. Sustained Qb ≥200 ml/min and spKt/V ≥1.2 (or URR ≥ 63) on stable
             hemodialysis/hemodiafltration prescription during screening with prescription (time,
             dialyzer, blood flow [Qb], dialysate flow rate [Qd] and bicarbonate concentration)
             expected to remain unchanged during study

          8. Heparin dose (if used) must be stable during screening and expected to be stable
             during the study

          9. Subjects must be receiving dietary counseling appropriate for ESRD patients treated
             with hemodialysis/hemodiafiltration as per local guidelines, which includes dietary
             potassium restriction.

        Exclusion Criteria:

          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca,
             including ZS Pharma staff and/or staff at the study site)

          2. Hemoglobin <9 g/dL on screening (as assessed on Visit 1)

          3. Lack of compliance with hemodialysis prescription (both number and duration of
             treatments) during the two-week period preceding screening (100% compliance required)

          4. Patients treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium),
             calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7
             days before screening or anticipated in requiring any of these agents during the study

          5. Myocardial infarction, acute coronary syndrome, stroke, seizure or a
             thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but
             excluding vascular access thrombosis) within 12 weeks prior to randomization

          6. Laboratory diagnosis of hypokalemia (K < 3.5 mmol/L), hypocalcemia (Ca < 8.2 mg/dL;
             for Japan hypocalcemia is defined as albumin-corrected Ca < 8.0 mg/dL), hypomagnesemia
             (Mg < 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4
             weeks preceding randomization

          7. Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not
             considered screening failure, sampling or full screening can be postponed to a later
             time as applicable).

          8. Severe leukocytosis (>20× 10^9/L) or thrombocytosis (≥450 × 10^9/L) during screening

          9. Polycythemia (Hb >14 g/dL) during screening

         10. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization

         11. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics
             for hyperammonemia within 7 days prior to the first dose of study drug

         12. Patients unable to take oral ZS drug mix

         13. Scheduled date for living donor kidney transplant

         14. Patients with a life expectancy of less than 6 months

         15. Female patients who are pregnant or breastfeeding

         16. Females of childbearing potential, unless using contraception as detailed in the
             protocol or sexual abstinence.

         17. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof

         18. Participation in another clinical study with an investigational product during the
             last 1 month before screening

         19. Any medical condition, including active, clinically significant infection, that in the
             opinion of the investigator or Sponsor may pose a safety risk to a patient in this
             study, which may confound safety or efficacy assessment and jeopardize the quality of
             the data, or may interfere with study participation

         20. Presence of cardiac arrhythmias or conduction defects that require immediate treatment

         21. History of alcohol or drug abuse within 2 years prior to randomization

         22. Previous randomization in the present study