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HyperkalemiaPhase 3NCT02088073

Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.

A Phase 3 study testing Sodium zirconium cyclosilicate in people with Hyperkalemia, run by ZS Pharma, Inc. at 46 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hyperkalemia
What is being tested?
Sodium zirconium cyclosilicate
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
258 participants
Where
46 sitesin 3 countries
Study dates
31 Mar 2014to 31 Jan 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

46 sites in 3 countries.

46 sites in 3 countries

United States38 sites

  • Study site

    Altoona, Pennsylvania

  • Study site

    Anniston, Alabama

  • Study site

    Atlantis, Florida

  • Study site

    Auburn, Maine

  • Study site

    Bradenton, Florida

  • Study site

    Brandon, Florida

  • Study site

    Brooksville, Florida

  • Study site

    Chattanooga, Tennessee

  • Study site

    Chesterfield, Michigan

  • Study site

    Columbus, Georgia

  • Study site

    Decatur, Georgia

  • Study site

    DeLand, Florida

  • Study site

    Edgewater, Florida

  • Study site

    Evergreen Park, Illinois

  • Study site

    Flushing, New York

  • Study site

    Hawaiian Gardens, California

  • Study site

    Huntsville, Alabama

  • Study site

    Joliet, Illinois

  • Study site

    Kansas City, Missouri

  • Study site

    Las Vegas, Nevada

  • Study site

    Los Angeles, California

  • Study site

    Miami, Florida

  • Study site

    Miami Lakes, Florida

  • Study site

    New Smyrna Beach, Florida

  • Study site

    Ocala, Florida

  • Study site

    Orangeburg, South Carolina

  • Study site

    Paramount, California

  • Study site

    Phoenix, Arizona

  • Study site

    Providence, Rhode Island

  • Study site

    Riverside, California

  • Study site

    San Antonio, Texas

  • Study site

    Scottsboro, Alabama

  • Study site

    Shreveport, Louisiana

  • Study site

    Summerfield, Florida

  • Study site

    Sumter, South Carolina

  • Study site

    Tampa, Florida

  • Study site

    Tempe, Arizona

  • Study site

    Winter Park, Florida

Other trials in United States

Australia5 sites

  • Study site

    Gosford, New South Wales

  • Study site

    Heidelberg, Victoria

  • Study site

    Melbourne, Victoria

  • Study site

    Parkville, Victoria

  • Study site

    Woolloongabba, Queensland

Other trials in Australia

South Africa3 sites

  • Study site

    Meyerspark

  • Study site

    Port Elizabeth

  • Study site

    Somerset West

Other trials in South Africa

About this study

Official 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.

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).

Read the detailed description

Approximately 275 subjects with hyperkalemia (two consecutive i-STAT potassium levels ≥ 5.1 mmol/l, taken 60 minutes apart at baseline) will be enrolled in the Open-label Acute Phase to provide 232 subjects in the Double Blind Randomized Maintenance Phase.

Initially all subjects will receive open-label ZS at a dose of 10g three times a day (tid) for 48 hours (AP). Subjects who achieve normokalemia (i-STAT potassium values between 3.5 to 5.0 mmol/l, inclusive) on the morning of Study Day 3 (after 6 doses of 10g ZS) will then, in a double-blind fashion, be randomized 4:4:4:7 to receive one of three doses of ZS (5g, 10g or 15g) or placebo control, qd for the following 28 days (DBRMP).

Safety and tolerability will be assessed on an ongoing basis by an Independent Data Monitoring Committee (iDMC). Each active dose group in the DBRMP will consist of 49 subjects and the placebo control group will consist of 85 subjects for a total of 232 subjects to detect a 0.6 effect size difference between each ZS dose (from highest to lowest) and placebo control; the 4:4:4:7 allocation optimizes the multiple comparisons to the placebo control for the DBRMP.

Conditions
Hyperkalemia
Being tested
Sodium zirconium cyclosilicate, Placebo
Medical subject headings
Hyperkalemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sodium zirconium cyclosilicateDrug

    Also called ZS; Microporous, Fractionated, Protonated Zirconium Silicate; Zirconium Silicate

    Sodium zirconium cyclosilicate

  • PlaceboDrug

    Also called Silicilate microcrystaline cellulose

    Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days (maintenance phase)

Study groups in NCT02088073
Study groupRoleWhat they receive
Sodium zirconium cyclosilicate 10 g three times dailyExperimentalSodium zirconium cyclosilicate 10 g three times daily for 48 hours (acute phase)
Receives: Drug: Sodium zirconium cyclosilicate
Placebo once dailyPlacebo comparatorRandomized to mimic doses of experimental drug administered once daily with breakfast for 28 days.
Receives: Drug: Placebo
Sodium zirconium cyclosilicate 5 g once dailyExperimentalSodium zirconium cyclosilicate (ZS) 5 g once daily for 28 days (maintenance phase)
Receives: Drug: Sodium zirconium cyclosilicate
Sodium zirconium cyclosilicate 10 g once dailyExperimentalSodium zirconium cyclosilicate (ZS) 10 g once daily for 28 days (maintenance phase)
Receives: Drug: Sodium zirconium cyclosilicate
Sodium zirconium cyclosilicate 15 g once dailyExperimentalSodium zirconium cyclosilicate (ZS) 15 g once daily for 28 days (maintenance phase)
Receives: Drug: Sodium zirconium cyclosilicate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population).

    The least squares means (LSMeans) are dervied from a mixed effects model of serial log transformed S-K values between Days 8 and 29 with patients as a random effect and the following fixed effects terms: MP treatment group; AP baseline eGFR; AP and MP baseline S-K levels, age categories (<55, 55-64, >= 65 years); and binary indicators for RAAS inhibitors use, CKD, CHF, and DM. The LSmeans estimate obtained from the above model is back-transformed and presented as the lsmeans of all available S-K values during the Maintenance phase study Days 8 to 29.

    Measured: 22 Days; Maintenance Phase Days 8 - 29, inclusive.

Secondary outcomes (14)

  1. The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT).

    The number of normokalemic days during the Maintenance Phase Study Days 8 to 29 is calculated assuming that the interval between assessments is normokalemic only if both the beginning and end assessments for that time interval display normal S-K values (i.e. 3.5 - 5.0 mmol/L)

    Measured: 22 days; Maintenance Phase Day 8 - 29, inclusive.

  2. Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit .

    Measured: Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.

  3. Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive .

    Measured: Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.

  4. Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.

    Measured: Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.

  5. Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.

    Measured: Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.

  6. Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L)

    Measured: Maintenance Phase baseline to maintenance Phase Study Day 29/Exit.

  7. Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8

    Measured: 22 days; Maintenance Phase Day 8 - 29

  8. Proportion of Subjects Who Remained Normokalemic During Maintenance Phase

    Measured: Maintenance Phase Study Days 1, 2, 5, 8, 12, 15, 19, 22, 26, 29, and 35, inclusive.

  9. Median Time to Relapse in S-K Values

    Median time to relapse in S-K values (return to original Acute Phase S-K baseline value)

    Measured: Maintenance phase Study Day 1 to Study Day 29/Exit.

  10. Exponential Rate of Change in S-K Values During the Acute Phase at 24 Hours and 48 Hours of Study Drug Treatment.

    Measured: Acute Phase 24 hours and Acute Phase 48 hours.

  11. Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.

    Measured: All measured time intervals post dose during the Acute Phase.

  12. Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.

    Measured: All measured time intervals post dose during the Acute Phase.

  13. Proportion of Subjects Who Achieve Normokalemia During the Acute Phase at 24 and 48 Hours After Start of Dosing

    Measured: Through 48 hours acute phase

  14. Median Time to Normalization (3.50-5.0 mmol/L) in S-K Levels in the 48 Hours of Initial Treatment

    Measured: Through 48 hours acute phase

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2014 (estimated)
  2. Study start31 Mar 2014
  3. Primary completion31 Aug 2014
  4. Study completion31 Jan 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
258 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02088073
Sponsor's protocol ID
ZS-004
Status last verified
Nov 2018
First submitted
12 Mar 2014
Last updated
7 Dec 2018
Data monitoring committee
Yes

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.

    PubMed 32588430

  • 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.

    PubMed 31791288

  • 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.

    PubMed 25402495

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sodium zirconium cyclosilicate in people with Hyperkalemia, run by ZS Pharma, Inc. at 46 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in United States, Australia, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population). (time frame: 22 Days; Maintenance Phase Days 8 - 29, inclusive.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02088073, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2018.

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