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

NCT02163499 | Completed Phase 3 Results

• 1 other identifier: ZS-005
• Study Type: interventional
• Target: 751
• Locations: 7 countries
• Sites: 50

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.

Conditions

Hyperkalemia

Outcome Measures

Primary Outcomes (2)

• Percent of Participants With Restoration of Normal Serum Potassium (S-K) Values (3.5 to 5.0 mmol/L, Inclusive) at the End of the Acute Phase

  Percentage of subjects with S-K values between 3.5 and 5.0 mmol/L, inclusive at the end of the Acute Phase - ITT Population

  72 Hours

• Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 365

  Percentage of subjects with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase - ITT Population

  Study Days 85 to 365

Secondary Outcomes (2)

• Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12

  Study Days 85 to 365

• Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12.

  Study days 85 to 365

Study Arms (1)

Sodium Zirconium Cyclosilicate

EXPERIMENTAL

Drug: Sodium Zirconium Cyclosilicate

Interventions

Sodium Zirconium Cyclosilicate 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.

Also known as: ZS

Sodium Zirconium Cyclosilicate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ZS Pharma, Inc.: lead

Study Sites (50)

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Scottsboro, Alabama, 35768, United States

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Tempe, Arizona, 85284, United States

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Tucson, Arizona, 85724, United States

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Chula Vista, California, 90717, United States

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Los Angeles, California, 90022, United States

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Paramount, California, 90723, United States

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Riverside, California, 92505, United States

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Sacramento, California, 95825, United States

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Whittier, California, 90603, United States

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Denver, Colorado, 80230, United States

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Brandon, Florida, 33511, United States

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DeLand, Florida, 32720, United States

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Hudson, Florida, 34667, United States

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Lauderdale Lakes, Florida, 33313, United States

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Miami, Florida, 33015, United States

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Miami, Florida, 33125, United States

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Miami Lakes, Florida, 33018, United States

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New Smyrna Beach, Florida, 32168, United States

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Tampa, Florida, 33614, United States

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Winter Park, Florida, 32789, United States

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Columbus, Georgia, 31901, United States

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Evergreen Park, Illinois, 60805, United States

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Joliet, Illinois, 60435, United States

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Paducah, Kentucky, 42003, United States

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Shreveport, Louisiana, 71101, United States

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Chesterfield, Michigan, 48047, United States

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Kansas City, Missouri, 64411, United States

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St Louis, Missouri, 63110, United States

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Great Neck, New York, 11021, United States

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Providence, Rhode Island, 02903, United States

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Orangeburg, South Carolina, 29118, United States

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Sumter, South Carolina, 29150, United States

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Chattanooga, Tennessee, 37408, United States

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San Antonio, Texas, 78215, United States

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San Antonio, Texas, 78229, United States

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St. George, Utah, 84770, United States

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Gosford, New South Wales, 2250, Australia

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Woolloongabba, Queensland, 4102, Australia

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Heidelberg, Victoria, 3084, Australia

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Melbourne, Victoria, 3073, Australia

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Parkville, Victoria, 3050, Australia

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Berlin, 13353, Germany

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Stuttgart, 70376, Germany

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Amsterdam, 1105 AZ, Netherlands

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Lasi, 700503, Romania

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Cape Town, 7925, South Africa

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Meyerspark, South Africa

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Port Elizabeth, 6001, South Africa

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Somerset West, 7130, South Africa

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Leicester, LE1 9HN, United Kingdom

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Related Publications (1)

• 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.

  PMID: 32030422 DERIVED

MeSH Terms

Conditions

Hyperkalemia

Interventions

sodium zirconium cyclosilicate

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: ZS Pharma, Inc

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Henrik Rasmussen, MD, PhD

  ZS Pharma, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2014
• First Posted: June 13, 2014
• Study Start: June 30, 2014
• Primary Completion: November 30, 2016
• Study Completion: November 30, 2016
• Last Updated: June 27, 2018
• Results First Posted: June 27, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); GB (1); DE (2); US (36); NL (1); RO (1); ZA (4)