Study of the Effect of SZC on Serum Potassium and Serum Bicarbonate in Patients With Hyperkalemia and Metabolic Acidosis Associated With Chronic Kidney Disease

A Double-blind Randomized Placebo-controlled Parallel Design Multicenter Phase IIIb Study of the Effect of Sodium Zirconium Cyclosilicate (SZC) on Serum Potassium and Serum Bicarbonate in Patients With Hyperkalemia and Metabolic Acidosis Associated With Chronic Kidney Disease (NEUTRALIZE)

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

NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, Phase IIIb study to investigate the safety and efficacy of SZC in patients with hyperkalemia and low bicarbonate (metabolic acidosis ).

The study will be conducted in the United States (US) at approximately 35 investigative sites.

After screening on Day 1, all eligible patients will receive open-label SZC for up to 48 hours. Patients who achieve normokalemia within 48 hours will be randomized 1:1 into the double-blind randomized treatment phase to receive SZC or placebo. Study treatment will end with the Day 29 visit, which will be followed by a follow-up visit 7 days after the last administration of study medication.

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