Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months

NCT ID: NCT02163499

Last Updated: 2018-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 751 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2016-11-30

Brief Summary

The Open-Label Maintenance Study contains an Acute Phase, in which subjects will be dosed with ZS 10 g three times daily (tid) for 24 to 72 hours, followed by a long-term Maintenance Phase.

Detailed Description

Subjects with 2 consecutive i STAT potassium values 5.1 mmol/L will enter the Acute Phase and receive ZS 10 g tid for 24 to 72 hours, depending on potassium values. Once normokalemia (i STAT potassium between 3.5 and 5.0 mmol/L, inclusive) is restored (whether after 24, 48 or 72 hours), subjects will be enrolled in the Maintenance Phase to be dosed with ZS at a starting dose of 5 g qd. Potassium (i STAT and central laboratory) will be measured weekly throughout the first month of study and every 4 weeks thereafter through Month 12. During the Maintenance Phase, the ZS dose may be increased or decreased in increments/decrements of 5 g qd up to a maximum of 15 g qd or a minimum of 5 g every other day based on i STAT potassium measurements as outlined below:

• > 5.0 mmol/L while receiving 5 g qd or 5 g every other day or > 5.5 mmol/L while receiving 10 g qd: increase ZS dose in 5 g qd increments to a maximum dose of 15 g qd

.• Between 3.0 and 3.4 mmol/L, inclusive: decrease ZS dose in 5 g qd decrements to a minimum dose of 5 g every other day; if a subject's i STAT potassium value remains between 3.0 and 3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from the study and receive standard of care treatment.

There is no limit to the number of dose titrations allowed. Subjects will receive up to 12 months of treatment with open-label ZS.

Conditions

Hyperkalemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Sodium Zirconium Cyclosilicate

Group Type: EXPERIMENTAL

Sodium Zirconium Cyclosilicate

Intervention Type: DRUG

Acute Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) for 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) based on i-STAT potassium measurements up to 12 months.

Interventions

Sodium Zirconium Cyclosilicate

Acute Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) for 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) based on i-STAT potassium measurements up to 12 months.

Intervention Type: DRUG

Other Intervention Names

ZS

Eligibility Criteria

Inclusion Criteria

• Provision of written informed consent.
• Over 18 years of age.
• Two consecutive i STAT potassium values, measured 60 (+/- 15) minutes apart, both >/= 5.1 mmol/L and measured within 1 day before the first dose of ZS on Acute Phase Study Day 1.
• Ability to have repeated blood draws or effective venous catheterization.
• Women of childbearing potential must be using 2 forms of medically acceptable contraception (at least 1 barrier method) and have a negative pregnancy test at Acute Phase Study Day 1. Women who are surgically sterile or those who are postmenopausal for at least 2 years are not considered to be of childbearing potential.
• Controlled diabetic subjects.

Exclusion Criteria

• Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to excessive fist clenching to make veins prominent, difficult or traumatic venipuncture, or history of severe leukocytosis or thrombocytosis.
• Subjects treated with lactulose, rifaximin, or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of ZS on Acute Phase Study Day 1.
• Subjects treated with sodium polystyrene sulfonate (SPS; eg, Kayexalate®) or calcium polystyrene sulfonate (eg, Resonium®) within 3 days prior to first dose of ZS on Acute Phase Study Day 1.
• Subjects with a life expectancy of less than 12 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.
• 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.
• Subjects randomized into the previous ZS-002, ZS-003, ZS-004, or ZS-004E studies.
• Documented GFR <15 mL/min within 90 days prior to study entry.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZS Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Henrik Rasmussen, MD, PhD

Role: STUDY_CHAIR

ZS Pharma, Inc.

Locations

Scottsboro, Alabama, United States

Tempe, Arizona, United States

Tucson, Arizona, United States

Chula Vista, California, United States

Los Angeles, California, United States

Paramount, California, United States

Riverside, California, United States

Sacramento, California, United States

Whittier, California, United States

Denver, Colorado, United States

Brandon, Florida, United States

DeLand, Florida, United States

Hudson, Florida, United States

Lauderdale Lakes, Florida, United States

Miami, Florida, United States

Miami, Florida, United States

Miami Lakes, Florida, United States

New Smyrna Beach, Florida, United States

Tampa, Florida, United States

Winter Park, Florida, United States

Columbus, Georgia, United States

Evergreen Park, Illinois, United States

Joliet, Illinois, United States

Paducah, Kentucky, United States

Shreveport, Louisiana, United States

Chesterfield, Michigan, United States

Kansas City, Missouri, United States

St Louis, Missouri, United States

Great Neck, New York, United States

Providence, Rhode Island, United States

Orangeburg, South Carolina, United States

Sumter, South Carolina, United States

Chattanooga, Tennessee, United States

San Antonio, Texas, United States

San Antonio, Texas, United States

St. George, Utah, United States

Gosford, New South Wales, Australia

Woolloongabba, Queensland, Australia

Heidelberg, Victoria, Australia

Melbourne, Victoria, Australia

Parkville, Victoria, Australia

Berlin, , Germany

Stuttgart, , Germany

Amsterdam, , Netherlands

Lasi, , Romania

Cape Town, , South Africa

Meyerspark, , South Africa

Port Elizabeth, , South Africa

Somerset West, , South Africa

Leicester, , United Kingdom

Countries

United States; Australia; Germany; Netherlands; Romania; South Africa; United Kingdom

References

Roger SD, Lavin PT, Lerma EV, McCullough PA, Butler J, Spinowitz BS, von Haehling S, Kosiborod M, Zhao J, Fishbane S, Packham DK. Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study. Nephrol Dial Transplant. 2021 Jan 1;36(1):137-150. doi: 10.1093/ndt/gfz285.

Reference Type: DERIVED

PMID: 32030422 (View on PubMed)

Other Identifiers

ZS-005

Identifier Type: -

Identifier Source: org_study_id