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

Study identifier:D9480C00022

ClinicalTrials.gov identifier:NCT04727528

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

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)

Medical condition

Hyperkalaemia

Phase

Phase 3

Healthy volunteers

Study drug

Sodium zirconium cyclosilicate, Placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 22 Mar 2021

Primary Completion Date: 14 Sept 2022

Study Completion Date: 14 Sept 2022

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2023 by AstraZeneca

Collaborators

Inclusion and exclusion 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

No locations available

Arms	Assigned Interventions
Experimental: Open-label correction phase (up to 48 hours) All eligible patients will receive SZC 10 g TID for up to 48 hours. Patients with POCT (Point-of-Care-Test) K+ ≥5.1 mmol/L after 24 hours will continue on SZC 10 g TID for another 24 hours. Patients who achieve normokalemia (defined as POCT K+ between 3.5 and 5.0 mmol/L inclusive) after receiving SZC 10 g TID for up to 48 hours will proceed to randomization. Patients with POCT K+ <3.5mmol/L at any time during the open-label phase will be withdrawn from study treatment and will be followed per protocol.	Drug: Sodium zirconium cyclosilicate Investigational medicinal product Other Name: SZC Drug: Placebo Plabeco comparator
Experimental: Randomized, placebo controlled phase (Day 2 or 3 to Day 29) Patients will be randomized to SZC 10 g QD or placebo 10 g QD. The dose of SZC/placebo will be titrated by increasing or decreasing the dose by 5 g increments at 1-week intervals to between 5 g every other day (QOD) and 15 g QD of the randomized phase to maintain normokalemia by POCT K+.	Drug: Sodium zirconium cyclosilicate Investigational medicinal product Other Name: SZC Drug: Placebo Plabeco comparator

Arms

Assigned Interventions

Experimental: Open-label correction phase (up to 48 hours)
All eligible patients will receive SZC 10 g TID for up to 48 hours. Patients with POCT (Point-of-Care-Test) K+ ≥5.1 mmol/L after 24 hours will continue on SZC 10 g TID for another 24 hours. Patients who achieve normokalemia (defined as POCT K+ between 3.5 and 5.0 mmol/L inclusive) after receiving SZC 10 g TID for up to 48 hours will proceed to randomization. Patients with POCT K+ <3.5mmol/L at any time during the open-label phase will be withdrawn from study treatment and will be followed per protocol.

Drug: Sodium zirconium cyclosilicate
Investigational medicinal product

Other Name: SZC

Drug: Placebo
Plabeco comparator

Experimental: Randomized, placebo controlled phase (Day 2 or 3 to Day 29)
Patients will be randomized to SZC 10 g QD or placebo 10 g QD. The dose of SZC/placebo will be titrated by increasing or decreasing the dose by 5 g increments at 1-week intervals to between 5 g every other day (QOD) and 15 g QD of the randomized phase to maintain normokalemia by POCT K+.

Drug: Sodium zirconium cyclosilicate
Investigational medicinal product

Other Name: SZC

Drug: Placebo
Plabeco comparator

Documents available

CSRsynopsis_redacted
Download
SAP_redacted
Download
CSP_redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]