Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.

NCT ID: NCT02088073

Last Updated: 2018-12-07

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

258 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2015-01-31

Brief Summary

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It is hypothesized that ZS is more effective than placebo control (alternative hypothesis) in maintaining mean double-blind randomized maintenance phase (DBRMP) Day 8-29 serum potassium levels (3.5 - 5.0 mmol/l, inclusive) among hyperkalemic subjects in whom normokalemia was established during the open-label acute phase versus no difference between each ZS dose (highest to lowest) versus placebo control (null hypothesis).

Detailed Description

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Approximately 275 subjects with hyperkalemia (two consecutive i-STAT potassium levels ≥ 5.1 mmol/l, taken 60 minutes apart at baseline) will be enrolled in the Open-label Acute Phase to provide 232 subjects in the Double Blind Randomized Maintenance Phase.

Initially all subjects will receive open-label ZS at a dose of 10g three times a day (tid) for 48 hours (AP). Subjects who achieve normokalemia (i-STAT potassium values between 3.5 to 5.0 mmol/l, inclusive) on the morning of Study Day 3 (after 6 doses of 10g ZS) will then, in a double-blind fashion, be randomized 4:4:4:7 to receive one of three doses of ZS (5g, 10g or 15g) or placebo control, qd for the following 28 days (DBRMP).

Safety and tolerability will be assessed on an ongoing basis by an Independent Data Monitoring Committee (iDMC). Each active dose group in the DBRMP will consist of 49 subjects and the placebo control group will consist of 85 subjects for a total of 232 subjects to detect a 0.6 effect size difference between each ZS dose (from highest to lowest) and placebo control; the 4:4:4:7 allocation optimizes the multiple comparisons to the placebo control for the DBRMP.

Conditions

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Hyperkalemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Sodium zirconium cyclosilicate 10 g three times daily

Sodium zirconium cyclosilicate 10 g three times daily for 48 hours (acute phase)

Group Type EXPERIMENTAL

Sodium zirconium cyclosilicate

Intervention Type DRUG

Sodium zirconium cyclosilicate

Placebo once daily

Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days (maintenance phase)

Sodium zirconium cyclosilicate 5 g once daily

Sodium zirconium cyclosilicate (ZS) 5 g once daily for 28 days (maintenance phase)

Group Type EXPERIMENTAL

Sodium zirconium cyclosilicate

Intervention Type DRUG

Sodium zirconium cyclosilicate

Sodium zirconium cyclosilicate 10 g once daily

Sodium zirconium cyclosilicate (ZS) 10 g once daily for 28 days (maintenance phase)

Group Type EXPERIMENTAL

Sodium zirconium cyclosilicate

Intervention Type DRUG

Sodium zirconium cyclosilicate

Sodium zirconium cyclosilicate 15 g once daily

Sodium zirconium cyclosilicate (ZS) 15 g once daily for 28 days (maintenance phase)

Group Type EXPERIMENTAL

Sodium zirconium cyclosilicate

Intervention Type DRUG

Sodium zirconium cyclosilicate

Interventions

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Sodium zirconium cyclosilicate

Sodium zirconium cyclosilicate

Intervention Type DRUG

Placebo

Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days (maintenance phase)

Intervention Type DRUG

Other Intervention Names

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ZS; Microporous, Fractionated, Protonated Zirconium Silicate; Zirconium Silicate Silicilate microcrystaline cellulose

Eligibility Criteria

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Inclusion Criteria

* Provision of written informed consent.
* Over 18 years of age.
* Two consecutive i-STAT potassium values, measured 60-minutes apart, both ≥5.1 mmol/l and measured within 1 day of the first ZS dose on AP Study Day 1.
* Ability to have repeated blood draws or effective venous catheterization.
* Women of childbearing potential must be using two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at AP Study Day 1. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential.

Exclusion Criteria

* Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen, history of severe leukocytosis or thrombocytosis.
* Subjects treated with lactulose, Xifaxan or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug.
* Subjects treated with resins (such as sevelamer acetate or sodium polystyrene sulfonate \[SPS; e.g. Kayexalate®\]), calcium acetate, calcium carbonate, or lanthanum carbonate, within 7 days prior to the first dose of study drug.
* Subjects with a life expectancy of less than 3 months.
* Subjects who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the subjects' tasks associated with the protocol.
* Women who are pregnant, lactating, or planning to become pregnant.
* Subjects with diabetic ketoacidosis.
* Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated.
* Known hypersensitivity or previous anaphylaxis to ZS or to components thereof.
* Randomization into the previous ZS-002 or ZS-003 studies.
* Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry.
* Subjects with cardiac arrhythmias that require immediate treatment.
* Subjects on dialysis.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ZS Pharma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Henrik Rasmussen, MD, PhD

Role: STUDY_CHAIR

ZS Pharma, Inc.

Locations

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Anniston, Alabama, United States

Site Status

Huntsville, Alabama, United States

Site Status

Scottsboro, Alabama, United States

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Phoenix, Arizona, United States

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Tempe, Arizona, United States

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Hawaiian Gardens, California, United States

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Los Angeles, California, United States

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Paramount, California, United States

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Riverside, California, United States

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Atlantis, Florida, United States

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Bradenton, Florida, United States

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Brandon, Florida, United States

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Brooksville, Florida, United States

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DeLand, Florida, United States

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Edgewater, Florida, United States

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Miami, Florida, United States

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Miami Lakes, Florida, United States

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New Smyrna Beach, Florida, United States

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Ocala, Florida, United States

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Summerfield, Florida, United States

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Tampa, Florida, United States

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Winter Park, Florida, United States

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Columbus, Georgia, United States

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Decatur, Georgia, United States

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Evergreen Park, Illinois, United States

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Joliet, Illinois, United States

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Shreveport, Louisiana, United States

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Auburn, Maine, United States

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Chesterfield, Michigan, United States

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Kansas City, Missouri, United States

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Las Vegas, Nevada, United States

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Flushing, New York, United States

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Altoona, Pennsylvania, United States

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Providence, Rhode Island, United States

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Orangeburg, South Carolina, United States

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Sumter, South Carolina, United States

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Chattanooga, Tennessee, United States

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San Antonio, Texas, United States

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Gosford, New South Wales, Australia

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Woolloongabba, Queensland, Australia

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Heidelberg, Victoria, Australia

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Melbourne, Victoria, Australia

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Parkville, Victoria, Australia

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Meyerspark, , South Africa

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Port Elizabeth, , South Africa

Site Status

Somerset West, , South Africa

Site Status

Countries

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United States Australia South Africa

References

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Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.

Reference Type DERIVED
PMID: 32588430 (View on PubMed)

Amin AN, Menoyo J, Singh B, Kim CS. Efficacy and safety of sodium zirconium cyclosilicate in patients with baseline serum potassium level >/= 5.5 mmol/L: pooled analysis from two phase 3 trials. BMC Nephrol. 2019 Dec 2;20(1):440. doi: 10.1186/s12882-019-1611-8.

Reference Type DERIVED
PMID: 31791288 (View on PubMed)

Kosiborod M, Rasmussen HS, Lavin P, Qunibi WY, Spinowitz B, Packham D, Roger SD, Yang A, Lerma E, Singh B. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014 Dec 3;312(21):2223-33. doi: 10.1001/jama.2014.15688.

Reference Type DERIVED
PMID: 25402495 (View on PubMed)

Other Identifiers

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ZS-004

Identifier Type: -

Identifier Source: org_study_id