Study of the Effect of SZC on Serum Potassium and Serum Bicarbonate in Patients With Hyperkalemia and Metabolic Acidosis Associated With Chronic Kidney Disease
Condition: Hyperkalaemia; Metabolic Acidosis; Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Acidosis; Hyperkalemia
Intervention: Sodium zirconium cyclosilicate; Placebo
Intervention description: Investigational medicinal product; Plabeco comparator
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, Phase IIIb study
Masking: Double (Participant, Investigator)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No

Summary:

      The main objective of this study is to evaluate the efficacy of SZC as compared to placebo in
      maintaining normal sK+ in patients with hyperkalemia and metabolic acidosis associated with
      CKD
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults aged ≥18 years

          -  Participants who have CKD stage 3-5, not on dialysis.

          -  POCT K+ level >5 mmol/L to ≤5.9 mmol/L and POCT bicarbonate levels between 16-20
             mmol/L inclusive prior to the first SZC dose on study Day 1

          -  Ability to have repeated blood draws or effective venous catheterization.

          -  Male and/or female. Contraceptive use by men or women should be consistent with local
             regulations regarding the methods of contraception for those participating in clinical
             studies.

          -  Capable of giving signed informed consent

        Exclusion Criteria:

          -  Participants with pseudohyperkalemia.

          -  Dialysis requirement or anticipated by the investigator to require dialysis therapy
             within 1 month, history of renal transplant, or life expectancy less than 3 months.

          -  Cardiac arrhythmias requiring immediate treatment.

          -  Active or suspected diabetic ketoacidosis.

          -  POCT bicarbonate low enough to need emergency intervention or treatment as judged by
             the investigator.

          -  Acute/chronic worsening renal function (eg, ≥30% decline in eGFR) in the 3 months
             before screening.

          -  Current acute decompensated HF, hospitalization due to decompensated HF within 4 weeks
             prior to screening, or myocardial infarction (MI), unstable angina, stroke or
             transient ischemic attack (TIA) within 12 weeks prior to screening.

          -  Coronary revascularization (percutaneous coronary intervention [PCI] or coronary
             artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to
             screening or planned to undergo any of these operations.

          -  Symptomatic hypotension.

          -  Current exacerbation of chronic obstructive pulmonary disease (COPD)/asthma or
             hospitalization due to exacerbation of COPD/asthma within 4 weeks of screening.

          -  Severe constipation, bowel obstruction or impaction, including abnormal post-operative
             bowel motility disorders

          -  Active malignancy requiring treatment.

          -  History of QT prolongation associated with other medications that required
             discontinuation of that medication.

          -  Congenital long QT syndrome.

          -  Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic
             sustained ventricular tachycardia. Patients with atrial fibrillation controlled by
             medication are permitted.

          -  QTcF (QT interval corrected by the Fridericia method) >550 msec.

          -  Active treatment (within 7 days prior to screening) with SZC, sodium bicarbonate,
             sodium polystyrene sulfonate, lactulose, or patiromer