Reduce Incidence of Pre-Dialysis Hyperkalaemia With Sodium Zirconium Cyclosilicate in Chinese Subjects
Condition: Hyperkalemia
MeSH terms: Hyperkalemia
Intervention: Sodium Zirconium Cyclosilicate; Placebo
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 SZC 5g 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 Placebo 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 134.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy and safety of Sodium Zirconium
      Cyclosilicate (SZC), as well as the appropriateness of the dosing mechanism, in Chinese
      end-stage renal disease (ESRD) patients on chronic haemodialysis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of signed and dated, written informed consent form prior to any mandatory
             study specific procedures, sampling, and analyses.

          2. Subject must be ≥ 18 years of age inclusive, at the time of signing the informed
             consent form.

          3. Subjects must have haemodialysis access consisting of an arteriovenous fistula, AV
             graft, or tunnelled (permanent) catheter which is expected to remain in place for the
             entire duration of the study.

          4. Receiving haemodialysis (or hemodiafiltration) 3 times a week for treatment of
             end-stage renal disease (ESRD) for at least 3 months before randomization.

          5. Pre-dialysis S-K > 5.4 mmol/L after long inter-dialytic interval and > 5.0 mmol/L
             after at least 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 haemodialysis /
             haemodiafltration prescription during screening with prescription (time, dialyzer,
             blood flow [Qb], dialysate flow rate [Qd] and bicarbonate concentration) expected to
             remain unchanged during study.

          8. Subjects must be receiving dietary counselling appropriate for ESRD subjects treated
             with haemodialysis / haemodiafiltration as per local guidelines, which includes
             dietary potassium restriction.

        Exclusion Criteria:

          1. 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.

          2. Pseudohyperkalaemia secondary to haemolyzed blood specimen (this situation is not
             considered screening failure, sampling or full screening can be postponed to a later
             time as applicable).

          3. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization.

          4. Presence of cardiac arrhythmias or conduction defects that require immediate
             treatment.

          5. Any medical condition, including active, clinically significant infection or liver
             disease, that in the opinion of the investigator or Sponsor may pose a safety risk to
             a subject in this study, which may confound safety or efficacy assessment and
             jeopardize the quality of the data, or may interfere with study participation.

          6. History of QT prolongation associated with other medications that required
             discontinuation of that medication; congenital long QT syndrome or QTc(f) > 550 msec;
             uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained
             ventricular tachycardia. Subjects with atrial fibrillation controlled by medication or
             with transient atrial fibrillation associated with dialysis or peridialytic period are
             permitted.

          7. Subjects treated with sodium polystyrene sulfonate (e.g. 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.

          8. Participation in another clinical study with an investigational product administered
             in the last 1 month before screening.

          9. Haemoglobin < 9 g/dL on screening (as assessed on Visit 1).

         10. Laboratory diagnosis of hypokalaemia (K < 3.5 mmol/L), hypocalcemia (Ca < 8.2 mg/d or
             albumin-corrected Ca < 8.0 mg/dL if the latter is used in local practice),
             hypomagnesemia (Mg < 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or
             less) in the 4 weeks preceding randomization.

         11. Severe leukocytosis (> 20 × 109/L) or thrombocytosis (≥ 450 × 109/L) during screening.

         12. Polycythaemia (Hb > 14 g/dL) during screening.

         13. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site).

         14. Judgment by the investigator that the subject should not participate in the study if
             the subject is unlikely to comply with study procedures, restrictions and
             requirements.

         15. Previous randomisation in the present study.

         16. For women only - currently pregnant (confirmed with positive pregnancy test or uterine
             ultrasound if pregnancy test is questionable) or breast-feeding.

         17. Females of childbearing potential, unless using contraception as detailed in the
             protocol or sexual abstinence.

         18. Lack of compliance with haemodialysis prescription (both number and duration of
             treatments) during the two-week period preceding screening (100% compliance required).

         19. Subjects unable to take investigational product drug mix.

         20. Scheduled date for living donor kidney transplant.

         21. Subjects with a life expectancy of less than 6 months.

         22. Known hypersensitivity or previous anaphylaxis to SZC or to components thereof.

         23. History of alcohol or drug abuse within 2 years prior to randomization.