HyperkalemiaPhase 3NCT02163499
Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months
A Phase 3 study testing Sodium Zirconium Cyclosilicate in people with Hyperkalemia, run by ZS Pharma, Inc. at 50 sites in 7 countries.
Trial 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. 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?
- No, everyone receives an active treatment
- How many people
- 751 participants
- Where
- 50 sitesin 7 countries
- Study dates
- 30 Jun 2014to 30 Nov 2016
- 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 (+/- 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.
Who cannot join
- 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.
Show all 14Show 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.
- 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.
Trial locations and contacts
50 sites in 7 countries.
50 sites in 7 countries
United States36 sites
Study site
Brandon, Florida, 33511
Study site
Chattanooga, Tennessee, 37408
Study site
Chesterfield, Michigan, 48047
Study site
Chula Vista, California, 90717
Study site
Columbus, Georgia, 31901
Study site
DeLand, Florida, 32720
Study site
Denver, Colorado, 80230
Study site
Evergreen Park, Illinois, 60805
Study site
Great Neck, New York, 11021
Study site
Hudson, Florida, 34667
Study site
Joliet, Illinois, 60435
Study site
Kansas City, Missouri, 64411
Study site
Lauderdale Lakes, Florida, 33313
Study site
Los Angeles, California, 90022
Study site
Miami, Florida, 33015
Study site
Miami, Florida, 33125
Study site
Miami Lakes, Florida, 33018
Study site
New Smyrna Beach, Florida, 32168
Study site
Orangeburg, South Carolina, 29118
Study site
Paducah, Kentucky, 42003
Study site
Paramount, California, 90723
Study site
Providence, Rhode Island, 02903
Study site
Riverside, California, 92505
Study site
Sacramento, California, 95825
Study site
San Antonio, Texas, 78215
Study site
San Antonio, Texas, 78229
Study site
Scottsboro, Alabama, 35768
Study site
Shreveport, Louisiana, 71101
Study site
St Louis, Missouri, 63110
Study site
St. George, Utah, 84770
Study site
Sumter, South Carolina, 29150
Study site
Tampa, Florida, 33614
Study site
Tempe, Arizona, 85284
Study site
Tucson, Arizona, 85724
Study site
Whittier, California, 90603
Study site
Winter Park, Florida, 32789
Australia5 sites
Study site
Gosford, New South Wales, 2250
Study site
Heidelberg, Victoria, 3084
Study site
Melbourne, Victoria, 3073
Study site
Parkville, Victoria, 3050
Study site
Woolloongabba, Queensland, 4102
South Africa4 sites
Study site
Cape Town, 7925
Study site
Meyerspark
Study site
Port Elizabeth, 6001
Study site
Somerset West, 7130
About this study
Official title: Multicenter, Multi-Dose, Open-Label Maintenance of Long-Term Safety and Efficacy of Sodium Zirconium Cyclosilicate (ZS) in Hyperkalemia
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.
Read the detailed description
Subjects with 2 consecutive i STAT potassium values 5.1 mmol/L will enter the Acute Phase and receive ZS 10 g tid for 24 to 72 hours, depending on potassium values. Once normokalemia (i STAT potassium between 3.5 and 5.0 mmol/L, inclusive) is restored (whether after 24, 48 or 72 hours), subjects will be enrolled in the Maintenance Phase to be dosed with ZS at a starting dose of 5 g qd. Potassium (i STAT and central laboratory) will be measured weekly throughout the first month of study and every 4 weeks thereafter through Month 12. During the Maintenance Phase, the ZS dose may be 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 based on i STAT potassium measurements as outlined below:
- > 5.0 mmol/L while receiving 5 g qd or 5 g every other day or > 5.5 mmol/L while receiving 10 g qd: increase ZS dose in 5 g qd increments to a maximum dose of 15 g qd
.• Between 3.0 and 3.4 mmol/L, inclusive: decrease ZS dose in 5 g qd decrements to a minimum dose of 5 g every other day; if a subject's i STAT potassium value remains between 3.0 and 3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from the study and receive standard of care treatment.
There is no limit to the number of dose titrations allowed. Subjects will receive up to 12 months of treatment with open-label ZS.
- Conditions
- Hyperkalemia
- Being tested
- Sodium Zirconium Cyclosilicate
- 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
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.
| Study group | Role | What they receive |
|---|---|---|
| Sodium Zirconium Cyclosilicate | Experimental | Not described Receives: Drug: Sodium Zirconium Cyclosilicate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Proportion of Subjects with mean S-K between 3.5 and 5.5 mmol/L during Extended Dosing Phase - ITT Population
Measured: Study Days 85 to 365
Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12.
Mean S-K levels months 3 to 12(EP Days 85, 113, 141, 176, 211, 239, 267, 295, 330, 365 and EOS),months 6 to 9, and months 9 to 12.
Measured: Study days 85 to 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2014 (estimated)
- Study start30 Jun 2014
- Primary completion30 Nov 2016
- Study completion30 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperkalemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 751 participants (actual)
Sponsor and investigators
- Lead sponsor
- ZS Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Henrik Rasmussen, MD, PhD, Study chair, ZS Pharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02163499
- Sponsor's protocol ID
- ZS-005
- Status last verified
- May 2018
- First submitted
- 11 Jun 2014
- Last updated
- 27 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
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.
PubMed 32030422
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Multi-Dose, Open-Label Maintenance of Long-Term Safety and Efficacy of Sodium Zirconium Cyclosilicate (ZS) in Hyperkalemia
- ClinicalTrials.gov ID
- NCT02163499
- Acronym / sponsor ID
- ZS-005
- Conditions
- Hyperkalemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 751 participants (actual)
- Lead sponsor
- ZS Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Jun 2014 (actual)
- Primary completion
- 30 Nov 2016 (actual)
- Study completion
- 30 Nov 2016 (actual)
- First posted
- 13 Jun 2014 (estimated)
- Results
- Posted 27 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Subjects with 2 consecutive i STAT potassium values 5.1 mmol/L will enter the Acute Phase and receive ZS 10 g tid for 24 to 72 hours, depending on potassium values. Once normokalemia (i STAT potassium between 3.5 and 5.0 mmol/L, inclusive) is restored (whether after 24, 48 or 72 hours), subjects will be enrolled in the Maintenance Phase to be dosed with ZS at a starting dose of 5 g qd. Potassium (i STAT and central laboratory) will be measured weekly throughout the first month of study and every 4 weeks thereafter through Month 12. During the Maintenance Phase, the ZS dose may be 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 based on i STAT potassium measurements as outlined below:
- > 5.0 mmol/L while receiving 5 g qd or 5 g every other day or > 5.5 mmol/L while receiving 10 g qd: increase ZS dose in 5 g qd increments to a maximum dose of 15 g qd
.• Between 3.0 and 3.4 mmol/L, inclusive: decrease ZS dose in 5 g qd decrements to a minimum dose of 5 g every other day; if a subject's i STAT potassium value remains between 3.0 and 3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from the study and receive standard of care treatment.
There is no limit to the number of dose titrations allowed. Subjects will receive up to 12 months of treatment with open-label ZS.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sodium Zirconium Cyclosilicate | Experimental | Drug: Sodium Zirconium Cyclosilicate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium Zirconium CyclosilicateAlso: ZSAcute 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. | Drug | Sodium Zirconium Cyclosilicate |
Primary outcome
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
Time frame: 72 Hours
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
Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 365
Time frame: Study Days 85 to 365
Percentage of subjects with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase - ITT Population
2 secondary outcomes
Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12
Time frame: Study Days 85 to 365
Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12.
Time frame: Study days 85 to 365
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32030422Roger 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henrik Rasmussen, MD, PhD study chair
ZS Pharma, Inc.
50 sites in 7 countries: see every site and its status.
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 50 sites in 7 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 6 inclusion and 14 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 27 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, Australia, South Africa, Germany, Netherlands and 2 more countries. 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. 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 27 Jun 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?
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 (time frame: 72 Hours). The study lists 2 primary outcomes in all. 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 NCT02163499, which also lists 1 linked publication.
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 27 Jun 2018.