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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01737697




Registration number
NCT01737697
Ethics application status
Date submitted
19/11/2012
Date registered
29/11/2012
Date last updated
12/10/2018

Titles & IDs
Public title
Safety & Efficacy of Zirconium Silicate in Mild to Moderate Hyperkalemia
Scientific title
Multicenter, Two-phase, Multi-dose, Prospective, Randomized, Double-blind, Placebo-Controlled Study of Safety and Efficacy of Microporous, Fractionated, Protonated Zirconium Silicate in Mild to Moderate Hyperkalemia
Secondary ID [1] 0 0
ZS-003
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 - Zirconium silicate (acute phase)
Treatment: Drugs - Zirconium silicate (subacute phase)
Treatment: Drugs - Placebo (acute phase)
Treatment: Drugs - Placebo ( subacute phase)

Experimental: Zirconium silicate (acute phase) - Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered 3 times (tid) daily with meals for 48 hours.

Placebo comparator: Placebo (acute phase) - Placebo ( silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals.

Experimental: Zirconium silicate (subacute phase) - Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered once a day prior to the morning meal for 12 days.

Placebo comparator: Placebo (subacute phase) - Placebo (silicified microcrystalline cellulose) randomized to mimic doses of experimental drug administered once a day (qd) prior to the morning meal for 12 days.


Treatment: Drugs: Zirconium silicate (acute phase)
Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered 3 times (tid) daily with meals for 48 hours.

Treatment: Drugs: Zirconium silicate (subacute phase)
Randomized oral doses (1.25g, 2.5g, 5g, and 10g) of microporous, fractionated, protonated zirconium silicate administered once a day prior to the morning meal for 12 days.

Treatment: Drugs: Placebo (acute phase)
Randomized to mimic doses of experimental drug administered 3 times (tid) daily with meals for 48 hours during the acute phase.

Treatment: Drugs: Placebo ( subacute phase)
Randomized to mimic doses of experimental drug administered once a day prior to the morning meal for 12 days during the subacute phase.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Exponential Rate of Change in Serum Potassium (S-K) Levels During the Initial 48 Hours of Study Drug Treatment.
Timepoint [1] 0 0
Through 48 hours acute phase
Primary outcome [2] 0 0
Exponential Rate of Change in S-K Levels in the Subacute Phase.
Timepoint [2] 0 0
Through 12 days subacute phase (Day 3 through Day 15)
Secondary outcome [1] 0 0
Percentage of Subjects Who Achieve Normalization in S-K Levels After 48 Hours of Treatment
Timepoint [1] 0 0
Through 48 hours acute phase
Secondary outcome [2] 0 0
Mean Change From Baseline in S-K at All Time Points Acute Phase
Timepoint [2] 0 0
Through 48 hours acute phase. In particular, at Baseline; 1, 2, 4 hour Post 1st Dose on Study Day 1; 0 hour Pre-dose, 1, 4 hour Post 1st Dose on Study Day 2; and 0 hour Pre-dose on Study Day 3.
Secondary outcome [3] 0 0
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase
Timepoint [3] 0 0
Through 48 hours acute phase. In particular, 1, 2, 4 hour Post 1st Dose on Study Day 1; 0 hour Pre-dose, 1, 4 hour Post 1st Dose on Study Day 2; and 0 hour Pre-dose on Study Day 3.
Secondary outcome [4] 0 0
Time Subjects Remain Normokalemic (Subacute Phase)
Timepoint [4] 0 0
Through 18 days (12 days treatment, 6 days follow-up) of subacute phase
Secondary outcome [5] 0 0
Percentage of Subjects Within Each Treatment Group Who Retained Normal S-K Values at End of Subacute Phase
Timepoint [5] 0 0
Through 18 days of subacute phase (12 days treatment, 6 days follow-up)
Secondary outcome [6] 0 0
Mean Change From Subacute Baseline in Serum Potassium at All Time Points.
Timepoint [6] 0 0
Through 18 days of subacute phase (12 days treatment, 6 days follow-up)
Secondary outcome [7] 0 0
Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points.
Timepoint [7] 0 0
Through 18 days of subacute phase (12 days treatment, 6 days follow-up)

Eligibility
Key inclusion criteria
* Provision of written informed consent.
* Over 18 years of age.
* Mean i-STAT potassium values between 5.0 - 6.5 mmol/l inclusive, at screening (Study Day 0).
* Ability to have repeated blood draws or effective venous catheterization.
* Women of childbearing potential must be practicing a highly effective method of birth control.
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 clinching hemolyzed blood specimen, severe leukocytosis or thrombocytosis.
* Subjects treated with lactulose, xifaxan or other nonabsorbed antibiotics for hyperammonemia within the last 7 days.
* Subjects treated with resins (such as Sevelamer acetate or Sodium polystyrene sulfonate [SPS; e.g. Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum carbonate, within the last 7 days.
* Subjects with a life expectancy of less than 3 months.
* Subjects who are HIV positive.
* 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 Ketoacidosis/Acidemia.
* 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.
* Previous treatment with ZS
* 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.
* Insulin-dependent diabetes mellitus
* 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
30/11/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/11/2013
Sample size
Target
Accrual to date
Final
754
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Renal Research - Gosford
Recruitment hospital [2] 0 0
Melbourne Renal Research Group - Reservoir
Recruitment postcode(s) [1] 0 0
02250 - Gosford
Recruitment postcode(s) [2] 0 0
03073 - Reservoir
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
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
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
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
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
Mississippi
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
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
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Utah

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

Ethics approval
Ethics application status

Summary
Brief summary
Acute Phase: It is hypothesized that ZS (zirconium silicate) is more effective than placebo control (alternative hypothesis) in lowering S-K levels in subjects with S-K between 5.0 - 6.5 mmol/l versus no difference between ZS and placebo control (null hypothesis).

Subacute Phase (randomized withdrawal): It is hypothesized that ZS once daily is more effective than placebo control (alternative hypotheses) in maintaining normokalemic levels (3.5 - 4.9 mmol/l) among subjects completing the Acute Phase versus no difference between each ZS dose and respective placebo controls (null hypotheses).
Trial website
https://clinicaltrials.gov/study/NCT01737697
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.
Friedman PA, Scott CG, Bailey K, Baumann NA, Albert D, Attia ZI, Ladewig DJ, Yasin O, Dillon JJ, Singh B. Errors of Classification With Potassium Blood Testing: The Variability and Repeatability of Critical Clinical Tests. Mayo Clin Proc. 2018 May;93(5):566-572. doi: 10.1016/j.mayocp.2018.03.013.
Packham DK, Rasmussen HS, Lavin PT, El-Shahawy MA, Roger SD, Block G, Qunibi W, Pergola P, Singh B. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015 Jan 15;372(3):222-31. doi: 10.1056/NEJMoa1411487. Epub 2014 Nov 21.
Public notes

Contacts
Principal investigator
Name 0 0
Henrik Rasmussen, MD
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/NCT01737697