Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.
Multicenter, Multi-phase, Multi-dose, Prospective, Double-blind, Placebo-controlled, Maintenance Study of Safety and Efficacy of ZS (Microporous, Fractionated, Protonated Zirconium Silicate) in Hyperkalemia.
1 other identifier
interventional
258
3 countries
46
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2014
Shorter than P25 for phase_3
46 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 12, 2014
CompletedFirst Posted
Study publicly available on registry
March 14, 2014
CompletedStudy Start
First participant enrolled
March 31, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2015
CompletedResults Posted
Study results publicly available
December 7, 2018
CompletedDecember 7, 2018
November 1, 2018
5 months
March 12, 2014
July 18, 2017
November 13, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population).
The least squares means (LSMeans) are dervied from a mixed effects model of serial log transformed S-K values between Days 8 and 29 with patients as a random effect and the following fixed effects terms: MP treatment group; AP baseline eGFR; AP and MP baseline S-K levels, age categories (\<55, 55-64, \>= 65 years); and binary indicators for RAAS inhibitors use, CKD, CHF, and DM. The LSmeans estimate obtained from the above model is back-transformed and presented as the lsmeans of all available S-K values during the Maintenance phase study Days 8 to 29.
22 Days; Maintenance Phase Days 8 - 29, inclusive.
Secondary Outcomes (14)
The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT).
22 days; Maintenance Phase Day 8 - 29, inclusive.
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit .
Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive .
Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.
Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.
Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.
- +9 more secondary outcomes
Study Arms (5)
Sodium zirconium cyclosilicate 10 g three times daily
EXPERIMENTALSodium zirconium cyclosilicate 10 g three times daily for 48 hours (acute phase)
Placebo once daily
PLACEBO COMPARATORRandomized to mimic doses of experimental drug administered once daily with breakfast for 28 days.
Sodium zirconium cyclosilicate 5 g once daily
EXPERIMENTALSodium zirconium cyclosilicate (ZS) 5 g once daily for 28 days (maintenance phase)
Sodium zirconium cyclosilicate 10 g once daily
EXPERIMENTALSodium zirconium cyclosilicate (ZS) 10 g once daily for 28 days (maintenance phase)
Sodium zirconium cyclosilicate 15 g once daily
EXPERIMENTALSodium zirconium cyclosilicate (ZS) 15 g once daily for 28 days (maintenance phase)
Interventions
Sodium zirconium cyclosilicate
Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days (maintenance phase)
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- ZS Pharma, Inc.lead
Study Sites (46)
Unknown Facility
Anniston, Alabama, United States
Unknown Facility
Huntsville, Alabama, United States
Unknown Facility
Scottsboro, Alabama, United States
Unknown Facility
Phoenix, Arizona, United States
Unknown Facility
Tempe, Arizona, United States
Unknown Facility
Hawaiian Gardens, California, United States
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Los Angeles, California, United States
Unknown Facility
Paramount, California, United States
Unknown Facility
Riverside, California, United States
Unknown Facility
Atlantis, Florida, United States
Unknown Facility
Bradenton, Florida, United States
Unknown Facility
Brandon, Florida, United States
Unknown Facility
Brooksville, Florida, United States
Unknown Facility
DeLand, Florida, United States
Unknown Facility
Edgewater, Florida, United States
Unknown Facility
Miami, Florida, United States
Unknown Facility
Miami Lakes, Florida, United States
Unknown Facility
New Smyrna Beach, Florida, United States
Unknown Facility
Ocala, Florida, United States
Unknown Facility
Summerfield, Florida, United States
Unknown Facility
Tampa, Florida, United States
Unknown Facility
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
Unknown Facility
Sumter, South Carolina, United States
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Chattanooga, Tennessee, United States
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San Antonio, Texas, United States
Unknown Facility
Gosford, New South Wales, Australia
Unknown Facility
Woolloongabba, Queensland, Australia
Unknown Facility
Heidelberg, Victoria, Australia
Unknown Facility
Melbourne, Victoria, Australia
Unknown Facility
Parkville, Victoria, Australia
Unknown Facility
Meyerspark, South Africa
Unknown Facility
Port Elizabeth, South Africa
Unknown Facility
Somerset West, South Africa
Related Publications (3)
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.
PMID: 32588430DERIVEDAmin 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.
PMID: 31791288DERIVEDKosiborod 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.
PMID: 25402495DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- AstraZeneca Clinical Study Information Center
- Organization
- ZS Pharma, Inc.
Study Officials
- STUDY CHAIR
Henrik Rasmussen, MD, PhD
ZS Pharma, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 12, 2014
First Posted
March 14, 2014
Study Start
March 31, 2014
Primary Completion
August 31, 2014
Study Completion
January 31, 2015
Last Updated
December 7, 2018
Results First Posted
December 7, 2018
Record last verified: 2018-11