Clinical trial NCT04727528: Study of the Effect of SZC on Serum Potassium and Serum Bicarbonate in Patients With Hyperkalemia and Metabolic Acidosis Associated With Chronic Kidney Disease
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hyperkalaemia
Metabolic Acidosis
Chronic Kidney Disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-01-27
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, Phase IIIb study
Primary purpose: TREATMENT

Brief 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

Detailed description: 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.

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

Primary outcomes:
measure: 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
timeFrame: Day 1 of randomization phase to Day 29
Secondary outcomes:
measure: Mean Serum Bicarbonate at Day 29
timeFrame: Day 29
measure: 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)
timeFrame: Day 1 to Day 29 of randomization phase
measure: Occurrence (Yes/no) of Participants Having Serum Bicarbonate ≥22 mmol/L
timeFrame: Day 1 to Day 29 of randomization phase
measure: Occurrence (Yes/no) of Participants Having an Increase in Serum Bicarbonate of Greater Than or Equal to 2 mmol/L From Baseline (Day 1) to EOT Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate)
timeFrame: Day 1 to Day 29 of randomization phase
measure: Participants Having Normal sK+ at EOT and an Increase in Serum Bicarbonate of ≥3 mmol/L From Baseline Without Need for Rescue Treatment for Metabolic Acidosis (Low Bicarbonate) or Hyperkalemia
timeFrame: Day 1 to Day 29 of randomization phase
measure: Occurrence (Yes/no) of Patients Having a Normal sK+ Between 3.5 and 5.0 mmol/L Inclusive and Bicarbonate ≥22 mmol/L at Day 29 Without Need for Rescue Treatment for Hyperkalemia or Metabolic Acidosis (Low Bicarbonate)
timeFrame: Day 1 to Day 29 of randomization phase
measure: Occurrence (Yes/no) of Participants Needing Rescue Treatment for Low Sodium Bicarbonate
timeFrame: Day 1 to Day 29 of randomization phase
Other outcomes:
Locations:
city: Florence
country: United States
facility: Research Site
state: Alabama
city: Chula Vista
country: United States
facility: Research Site
state: California
city: Downey
country: United States
facility: Research Site
state: California
city: El Centro
country: United States
facility: Research Site
state: California
city: S. Gate
country: United States
facility: Research Site
state: California
city: Victorville
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: Columbus
country: United States
facility: Research Site
state: Georgia
city: Hinsdale
country: United States
facility: Research Site
state: Illinois
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Bronx
country: United States
facility: Research Site
state: New York
city: Asheville
country: United States
facility: Research Site
state: North Carolina
city: New Bern
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Shenandoah
country: United States
facility: Research Site
state: Texas
city: Alexandria
country: United States
facility: Research Site
state: Virginia
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Bellevue
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: Research Site
Study officials:
References: