Keeping RAASi Treatment With Optimal Potassium Control

Inclusion Criteria:

• Patients must present serum potassium levels of 5.5-6.5 mEq/L at patient selectionvisit (V0)

• Patients must present serum potassium levels of 5.0-6.5 mEq/L at randomization visit (V1).

• Provision of patient or legal representative informed consent prior to any studyspecific procedures.

• Individuals receiving background standard of care for HF and treated according tolocally recognized guidelines. Specific treatment should include RAASi and/or MRAtreatment at first consultation and at least should have been stable for ≥ 4 weeksat maximum tolerated doses.

• Patients with CKD not on dialysis (Stages 2-5: estimated glomerular filtration rate (eGFR) between 15-60 ml/min/1,73m2 or eGFR between 60-90 ml/min/ 1.73 m2 withalbuminuria/creatinuria (> 30 mg/g) in the previous three months). The estimated GFRcan be reported by the laboratory or calculated by the researcher with serumcreatinine, age, and sex (CKD-EPI equation).

• 18 years at the time of signing ICF.

• Negative pregnancy test (urine or serum) for female subjects of childbearingpotential.

• Female subjects must be 1 year post-menopausal, surgically sterile, or using anacceptable method of contraception (an acceptable method of contraception is definedas a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign ICF) and for 3 months after the last dose of SZC. Inaddition, oral contraceptives, approved contraceptive implant, long-term injectablecontraception, intrauterine device, or tubal ligation are allowed. Oralcontraception alone is not acceptable; additional barrier methods in conjunctionwith spermicide must be used.

Exclusion Criteria:

• Involvement in the planning and/or conduct of the study (applies to bothInvestigator staff and/or staff at the study site).

• Previous enrollment or randomization in the present study.

• HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis,hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease.

• Current acute decompensated HF, hospitalization due to decompensated HF, myocardialinfarction, unstable angina, stroke or transient ischemic attack within 12 weeksprior to enrollment.

• Coronary revascularization (percutaneous coronary intervention or coronary arterybypass grafting or valvular repair/replacement within 12 weeks prior to enrollmentor planned to undergo any of these operations after randomization).

• Implantation of a Cardiac Resynchronization Therapy (CRT) device or ImplantableCardioverter Defibrillator (ICD) within 12 weeks prior to enrollment or intent toperform atrial fibrillation ablation or to implant a CRT or ICD device.

• Previous cardiac transplantation or implantation of a ventricular assistance deviceor similar device, or transplantation or implantation expected after randomization

• Oropharingeal dysfunction that precludes normal swallow.

• Female who is pregnant, breast-feeding or intends to become pregnant or is ofchild-bearing potential and not using a highly effective contraceptive method.

• Patients with amputated limbs or pacemaker devices will be excluded of bioimpedanceanalysis.

• Participation in another clinical study with an investigational product during thelast 6 months.

• Patients with a known hypersensitivity to SZC or any of the excipients of theproduct.

• Treated with potassium binding resins such as sodium polystyrene sulfonate (SPS;e.g. Kayexalate®) or calcium polystyrene sulfonate (CPS; e.g. Resonium®) or thecation exchange polymer, patiromer sorbitex calcium (Veltassa®), within 7 days priorto the first dose of study drug.

• Judgment by the investigator that the subject should not participate in the study ifthe subject is unlikely to comply with study procedures, restrictions andrequirements.

• Subjects with a family history of long QT syndrome, presence of cardiac arrhythmiasor conduction defects that require immediate treatment, or a QTc (corrected QTinterval) of ≥ 550 msec.

• History of QT prolongation associated with other medications that requireddiscontinuation of that medications.

• Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomaticsustained ventricular tachycardia. Subjects with atrial fibrillation controlled bymedication are permitted.