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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02163499




Registration number
NCT02163499
Ethics application status
Date submitted
11/06/2014
Date registered
13/06/2014
Date last updated
27/06/2018

Titles & IDs
Public title
Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months
Scientific title
Multicenter, Multi-Dose, Open-Label Maintenance of Long-Term Safety and Efficacy of Sodium Zirconium Cyclosilicate (ZS) in Hyperkalemia
Secondary ID [1] 0 0
ZS-005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hyperkalemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sodium Zirconium Cyclosilicate

Experimental: Sodium Zirconium Cyclosilicate -


Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
72 Hours
Primary outcome [2] 0 0
Percentage of Participants With Mean S-K Values = 5.1 mmol/L During Extended Dosing Phase Days 85 to 365
Timepoint [2] 0 0
Study Days 85 to 365
Secondary outcome [1] 0 0
Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12
Timepoint [1] 0 0
Study Days 85 to 365
Secondary outcome [2] 0 0
Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12.
Timepoint [2] 0 0
Study days 85 to 365

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Other
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/11/2016
Sample size
Target
Accrual to date
Final
751
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
- Gosford
Recruitment hospital [2] 0 0
- Woolloongabba
Recruitment hospital [3] 0 0
- Heidelberg
Recruitment hospital [4] 0 0
- Melbourne
Recruitment hospital [5] 0 0
- Parkville
Recruitment postcode(s) [1] 0 0
2250 - Gosford
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3073 - Melbourne
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Rhode Island
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Utah
Country [18] 0 0
Germany
State/province [18] 0 0
Berlin
Country [19] 0 0
Germany
State/province [19] 0 0
Stuttgart
Country [20] 0 0
Netherlands
State/province [20] 0 0
Amsterdam
Country [21] 0 0
Romania
State/province [21] 0 0
Lasi
Country [22] 0 0
South Africa
State/province [22] 0 0
Cape Town
Country [23] 0 0
South Africa
State/province [23] 0 0
Meyerspark
Country [24] 0 0
South Africa
State/province [24] 0 0
Port Elizabeth
Country [25] 0 0
South Africa
State/province [25] 0 0
Somerset West
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Leicester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ZS Pharma, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02163499
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Henrik Rasmussen, MD, PhD
Address 0 0
ZS Pharma, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02163499