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

Phase 3TerminatedNCT04727528

AstraZeneca39 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Hyperkalaemia Metabolic Acidosis Chronic Kidney Disease

Interventions

Sodium zirconium cyclosilicateDRUG

Investigational medicinal product

PlaceboDRUG

Plabeco comparator

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

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

Locations (30)

Outcomes

Primary Outcomes

Occurrence (Yes/no) of Participants Having Normal Serum Potassium (sK+) Between 3.5 and 5.0 mmol/L Inclusive at End of Treatment (EOT) Without Need for Rescue Treatment for Hyperkalemia at Any Point During the Randomized Phase

Response was defined as a subject having serum potassium (sK+) within 3.5-5.0 mmol/L at the EOT visit, and no use of rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period. Participants who used rescue therapy for hyperkalaemia at any point during the randomized placebo-controlled period were assigned a non-response. Participants who died prior to the EOT visit were treated as non-response. Participants who were lost to follow-up prior to the EOT visit had response treated as missing.

Time frame: Day 1 of randomization phase to Day 29

Secondary Outcomes

Mean Serum Bicarbonate at Day 29

Least-squares mean calculated with a repeated measures analysis of covariance model where the dependent variable was post randomization serum bicarbonate and with fixed terms for randomized treatment group and serum bicarbonate.

Time frame: Day 29

Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 3 mmol/L From Baseline to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)

Occurrence (yes/no) of participants having an increase in serum bicarbonate of greater than or equal to 3 mmol/L from baseline (Day 1) to EOT (Day 29) without need for rescue treatment for metabolic acidosis (low bicarbonate). Response was defined as a participant with an increase in serum bicarbonate greater than or equal to 3 mmol/L at the EOT visit without the need for rescue therapy for low bicarbonate. Participants who used rescue therapy for low bicarbonate at any point during the randomized placebo-controlled period had their last observation prior to rescue therapy carried forward. Participants who were lost to follow-up prior to the EOT visit had response treated as missing. Logistic regression model included response status (response / non-response) as the dependent variable and randomized treatment as an independent factor. Participants who died prior to the EOT visit were assigned a non-response.

Data from ClinicalTrials.gov

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Florence, Alabama, United States

Research Site

Chula Vista, California, United States

Research Site

Downey, California, United States

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El Centro, California, United States

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South Gate, California, United States

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Victorville, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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Coral Gables, Florida, United States

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Columbus, Georgia, United States

...and 20 more locations