Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04727528
Recruitment Status : Recruiting
First Posted : January 27, 2021
Last Update Posted : June 14, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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

Condition or disease Intervention/treatment Phase
Hyperkalaemia Metabolic Acidosis Chronic Kidney Disease Drug: Sodium zirconium cyclosilicate Drug: Placebo Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: NEUTRALIZE is a prospective, randomized, double-blind, placebo-controlled, parallel, multicenter, Phase IIIb study
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 22, 2021
Estimated Primary Completion Date : October 2, 2021
Estimated Study Completion Date : October 2, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 i- STAT 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 i-STAT 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 i-STAT 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 i-STAT K+.
Drug: Sodium zirconium cyclosilicate
Investigational medicinal product
Other Name: SZC

Drug: Placebo
Plabeco comparator




Primary Outcome Measures :
  1. Serum potassium [ Time Frame: From baseline to Day 29 ]
    Occurrence (yes/no)of patients having normal sK+ between 3.5 and 5.0 mmol/L inclusive at EOT without need for rescue treatment for hyperkalemia at any point during the randomized phase


Secondary Outcome Measures :
  1. Serum bicarbonate [ Time Frame: From baseline to Day 29 ]
    Mean change in serum bicarbonate at Day 29 compared to baseline (Day 1)

  2. Increase in serum bicarbonate of ≥3 mmol/L [ Time Frame: From baseline to Day 29 ]
    Occurrence (yes/no) of patients having an increase in serum bicarbonate of ≥3 mmol/L from baseline (Day 1) to EOT (Day 29) without need for rescue treatment for metabolic acidosis (low bicarbonate)

  3. Serum bicarbonate ≥22 mmol/L [ Time Frame: From baseline to Day 29 ]
    Occurrence (yes/no) of patients having serum bicarbonate ≥22 mmol/L

  4. Increase in serum bicarbonate of ≥2 mmol/L [ Time Frame: From baseline to Day 29 ]
    Occurrence (yes/no) of patients having an increase in serum bicarbonate of ≥2 mmol/L from baseline (Day 1) to EOT without need for rescue treatment for metabolic acidosis (low bicarbonate)

  5. Normal serum potassium between 3.5 and 5.0 mmol/L and an increase in serum bicarb of ≥3 mmol/L [ Time Frame: From baseline to Day 29 ]
    Occurrence (yes/no)of patients having normal sK+ between 3.5 and 5.0 mmol/L inclusive at EOT and an increase in serum bicarb of ≥3 mmol/L from baseline (Day 1) without need for rescue treatment for metabolic acidosis or hyperkalemia

  6. Normal serum potassium between 3.5 and 5.0 mmol/L and an increase in bicarb of ≥22 mmol/L [ Time Frame: Day 29 ]
    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)

  7. The need for rescue medication for low sodium bicarbonate [ Time Frame: From baseline to Day 29 ]
    Occurrence (yes/no) of patients needing rescue treatment for low sodium bicarbonate any time during the randomized phase


Other Outcome Measures:
  1. Spot urine ammonium [ Time Frame: From baseline to Day 29 ]
    Mean change in spot urine ammonium at Day 29 (End of Treatment) compared to baseline

  2. Spot urine citrate [ Time Frame: From baseline to Day 29 ]
    Mean change in spot urine citrate at Day 29 (End of Treatment) compared to baseline

  3. Spot urine anion gap [ Time Frame: From baseline to Day 29 ]
    Mean change in spot urine anion gap at Day 29 (End of Treatment) compared to baseline

  4. Spot urine ammonium to creatinine ratio [ Time Frame: From baseline to Day 29 ]
    Mean change in spot urine ammonium-to-creatinine ratio at Day 29 (End of Treatment) compared to baseline

  5. Serum aldosterone [ Time Frame: From baseline to Day 29 ]
    Mean change in serum aldosterone at Day 29 (End of Treatment) compared to baseline

  6. Adverse events [ Time Frame: From enrollment to up to 7 days post End of Treatment/Day 35 ]
    Percentage of subjects with treatment-emergent adverse events (TEAEs)

  7. Serious adverse events [ Time Frame: From enrollment to up to 7 days post End of Treatment/Day 35 ]
    Percentage of subjects experiencing TEAEs by severity

  8. Withdrawal of treatment due to an adverse event [ Time Frame: From enrollment to up to 7 days post End of Treatment/Day 35 ]
    TEAEs leading to discontinuation of study treatment will be summarized by treatment group



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults aged ≥18 years
  • Participants who have CKD stage 3 or 4
  • Two consecutive i-STAT K+ levels >5 mmol/L to ≤5.9 mmol/L and i-STAT bicarbonate levels between 16-20 mmol/L inclusive on 2 measurements 60 minutes apart (±15 minutes) 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 3 months, history of renal transplant, or life expectancy less than 3 months.
  • Cardiac arrhythmias requiring immediate treatment.
  • Active or suspected diabetic ketoacidosis.
  • i-STAT 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.
  • History of diabetic gastroparesis, bariatric surgery, bowel obstruction, swallowing 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 with SZC, sodium bicarbonate, sodium polystyrene sulfonate, lactulose, or patiromer

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04727528


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Layout table for location information
United States, Alabama
Research Site Recruiting
Florence, Alabama, United States, 35630
United States, California
Research Site Recruiting
Chula Vista, California, United States, 91910
Research Site Not yet recruiting
Downey, California, United States, 90242
Research Site Recruiting
El Centro, California, United States, 92243
Research Site Not yet recruiting
Sacramento, California, United States, 95817
Research Site Recruiting
Victorville, California, United States, 92395
United States, Colorado
Research Site Not yet recruiting
Aurora, Colorado, United States, 80045
Research Site Recruiting
Denver, Colorado, United States, 80230
United States, Connecticut
Research Site Recruiting
Middlebury, Connecticut, United States, 06762
United States, Georgia
Research Site Recruiting
Columbus, Georgia, United States, 31904
United States, Maryland
Research Site Recruiting
Takoma Park, Maryland, United States, 20912
United States, Missouri
Research Site Recruiting
Kansas City, Missouri, United States, 64111
United States, Nevada
Research Site Recruiting
Las Vegas, Nevada, United States, 89128
United States, New York
Research Site Recruiting
Bronx, New York, United States, 10461
United States, North Carolina
Research Site Recruiting
Asheville, North Carolina, United States, 28801
Research Site Recruiting
New Bern, North Carolina, United States, 28562
Research Site Recruiting
Winston-Salem, North Carolina, United States, 27103
United States, Oklahoma
Research Site Recruiting
Lawton, Oklahoma, United States, 73505
United States, Pennsylvania
Research Site Not yet recruiting
Danville, Pennsylvania, United States, 17822
Research Site Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15261
United States, Tennessee
Research Site Recruiting
Chattanooga, Tennessee, United States, 37404
Research Site Not yet recruiting
Memphis, Tennessee, United States, 38163
United States, Texas
Research Site Recruiting
Dallas, Texas, United States, 75230
Research Site Recruiting
Dallas, Texas, United States, 75246
Research Site Recruiting
Houston, Texas, United States, 77004
Research Site Recruiting
San Antonio, Texas, United States, 78258
Research Site Recruiting
Shenandoah, Texas, United States, 77384
United States, Virginia
Research Site Recruiting
Alexandria, Virginia, United States, 22304
Research Site Not yet recruiting
Norfolk, Virginia, United States, 23510
United States, Wisconsin
Research Site Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
AstraZeneca
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04727528    
Other Study ID Numbers: D9480C00022
First Posted: January 27, 2021    Key Record Dates
Last Update Posted: June 14, 2021
Last Verified: June 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Renal Insufficiency, Chronic
Acidosis
Hyperkalemia
Urologic Diseases
Renal Insufficiency
Acid-Base Imbalance
Metabolic Diseases
Water-Electrolyte Imbalance