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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02088073




Registration number
NCT02088073
Ethics application status
Date submitted
12/03/2014
Date registered
14/03/2014
Date last updated
7/12/2018

Titles & IDs
Public title
Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.
Scientific title
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.
Secondary ID [1] 0 0
ZS-004
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
Treatment: Drugs - Placebo

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

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

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

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

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


Treatment: Drugs: Sodium zirconium cyclosilicate
Sodium zirconium cyclosilicate

Treatment: Drugs: Placebo
Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days (maintenance phase)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population).
Timepoint [1] 0 0
22 Days; Maintenance Phase Days 8 - 29, inclusive.
Secondary outcome [1] 0 0
The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT).
Timepoint [1] 0 0
22 days; Maintenance Phase Day 8 - 29, inclusive.
Secondary outcome [2] 0 0
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit .
Timepoint [2] 0 0
Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.
Secondary outcome [3] 0 0
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive .
Timepoint [3] 0 0
Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.
Secondary outcome [4] 0 0
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.
Timepoint [4] 0 0
Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.
Secondary outcome [5] 0 0
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.
Timepoint [5] 0 0
Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.
Secondary outcome [6] 0 0
Median Time to Hyperkalemia (S-K = 5.1mmol/L)
Timepoint [6] 0 0
Maintenance Phase baseline to maintenance Phase Study Day 29/Exit.
Secondary outcome [7] 0 0
Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With = 2 Values on or After Maintenance Phase Study Day 8
Timepoint [7] 0 0
22 days; Maintenance Phase Day 8 - 29
Secondary outcome [8] 0 0
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase
Timepoint [8] 0 0
Maintenance Phase Study Days 1, 2, 5, 8, 12, 15, 19, 22, 26, 29, and 35, inclusive.
Secondary outcome [9] 0 0
Median Time to Relapse in S-K Values
Timepoint [9] 0 0
Maintenance phase Study Day 1 to Study Day 29/Exit.
Secondary outcome [10] 0 0
Exponential Rate of Change in S-K Values During the Acute Phase at 24 Hours and 48 Hours of Study Drug Treatment.
Timepoint [10] 0 0
Acute Phase 24 hours and Acute Phase 48 hours.
Secondary outcome [11] 0 0
Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.
Timepoint [11] 0 0
All measured time intervals post dose during the Acute Phase.
Secondary outcome [12] 0 0
Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.
Timepoint [12] 0 0
All measured time intervals post dose during the Acute Phase.
Secondary outcome [13] 0 0
Proportion of Subjects Who Achieve Normokalemia During the Acute Phase at 24 and 48 Hours After Start of Dosing
Timepoint [13] 0 0
Through 48 hours acute phase
Secondary outcome [14] 0 0
Median Time to Normalization (3.50-5.0 mmol/L) in S-K Levels in the 48 Hours of Initial Treatment
Timepoint [14] 0 0
Through 48 hours acute phase

Eligibility
Key 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.
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 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.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
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
31/03/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/01/2015
Sample size
Target
Accrual to date
Final
258
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
- Gosford
Recruitment postcode(s) [2] 0 0
- Woolloongabba
Recruitment postcode(s) [3] 0 0
- Heidelberg
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- 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
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maine
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Nevada
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
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Rhode Island
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
South Africa
State/province [18] 0 0
Meyerspark
Country [19] 0 0
South Africa
State/province [19] 0 0
Port Elizabeth
Country [20] 0 0
South Africa
State/province [20] 0 0
Somerset West

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

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT02088073
Trial related presentations / publications
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.
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.
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. Erratum In: JAMA. 2015 Feb 3;313(5):526. Dosage error in text.
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/NCT02088073