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CompletedNCT02163499Updated Jun 27, 2018Results posted

Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months

A Phase 3 interventional study of Sodium Zirconium Cyclosilicate in Hyperkalemia, sponsored by ZS Pharma, Inc.. Completed at 51 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-06-27.

Sponsored by ZS Pharma, Inc. · Phase 3, Interventional, and Supportive care

Phase
Phase 3
Study type
Interventional
Enrollment
751
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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 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potassium value remains between 3.0 and 3.4 mmol/L, inclusive, on the ZS 5 g every other day dose, the subject will be withdrawn from the study and receive standard of care treatment.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.

02

Conditions studied

  • Hyperkalemia

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03

In context

Hyperkalemia

122 studies on the registry are indexed under Hyperkalemia; 24 are open to participants now.

This study's enrollment of 751 is above the median of 80 across 92 interventional studies indexed under Hyperkalemia.

Browse Hyperkalemia studies →

Lead sponsor

ZS Pharma, Inc. is the lead sponsor of 8 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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.

Exclusion criteria

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.
05

Study design

Phase
Phase 3
Primary purpose
Supportive care
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
751 participants (actual)

Study arms

  • Experimental
    Sodium Zirconium Cyclosilicate

    Drug: Sodium Zirconium Cyclosilicate

Interventions

  • DrugSodium 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.

    Also known as: ZS

06

What researchers measure

Primary outcomes

  1. 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

    Time frame: 72 Hours

  2. 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

    Time frame: Study Days 85 to 365

Secondary outcomes

  1. 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

    Time frame: Study Days 85 to 365

  2. 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.

    Time frame: Study days 85 to 365

07

Results

Posted Jun 27, 2018

Participant flow

Participants took part in the study at 56 sites in the Unites States, Australia, South Africa, Germany, the United Kingdom and the Netherlands from 23 June 2014 to 04 November 2016

Acute Phase: ZS 10 g TID
Participant flow — Acute Phase: ZS 10 g TID
MilestoneSubject Disposition
Started751
Completed746
Not completed5
Withdrew: Participant's compliance1
Withdrew: Hypo- or hyperkalemia1
Withdrew: Protocol violation1
Withdrew: Physician decision1
Withdrew: Withdrawal by subject1
Extended Dosing Phase: ZS
Participant flow — Extended Dosing Phase: ZS
MilestoneSubject Disposition
Started746
Completed466
Not completed280
Withdrew: Adverse event51
Withdrew: Expected progression of ckd40
Withdrew: Hypokalemia9
Withdrew: Sponsor's decision5
Withdrew: Met ecg withdrawal criteria7
Withdrew: Withdrawal by subject81
Withdrew: Physician decision8
Withdrew: Lost to follow-up31
Withdrew: Protocol violation2
Withdrew: Death8
Withdrew: Subject compliance17
Withdrew: Hyperkalemia5
Withdrew: Various reasons16

Outcome measures

SecondaryProportion 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

Time frame:
Study Days 85 to 365
Reported as:
Number · Proportion of participants
Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 12
Proportion of participantsProportion
Proportion of Subjects With Mean S-K Between 3.5 and 5.5 mmol/L, Inclusive Months 3 to 120.985 (0.972 to 0.993)
SecondaryMean 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.

Time frame:
Study days 85 to 365
Reported as:
Mean · mmol/L
Mean S-K Levels Months 3 to 12, Months 6 to 9, and Months 9 to 12.
mmol/LMean S-K Levels Months 3 to 12,6 to 9, and 9 to 12
Acute Phase Baseline5.59 ± 0.425
Extended Dosing Days 85 to 365/End of Study4.66 ± 0.379
Extended Dosing Days 211 to 2674.68 ± 0.404
Extended Dosing Days 295 to 3654.62 ± 0.401
PrimaryPercent 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

Time frame:
72 Hours
Reported as:
Number · Percentage of participants
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 participantsPercentage
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 Phase77.9 (74.8 to 80.9)
PrimaryPercentage 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

Time frame:
Study Days 85 to 365
Reported as:
Number · Percentage of participants
Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 365
Percentage of participantsPercentage
Percentage of Participants With Mean S-K Values ≤ 5.1 mmol/L During Extended Dosing Phase Days 85 to 36588.4 (85.7 to 90.8)

Adverse events

Collected over One year. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Acute Phase: ZS0/751 (0%)1/751 (0.1%)11/751 (1.5%)
Extended Dosing Phase: ZS8/746 (1.1%)161/746 (21.6%)386/746 (51.7%)
Most frequent serious events
Showing 10 of 136
Most frequent serious events
EventAcute Phase: ZSExtended Dosing Phase: ZS
PneumoniaInfections and infestations0/75114/746
Cardiac failure congestiveCardiac disorders0/75111/746
Chest painGeneral disorders0/75111/746
OsteomyelitisInfections and infestations0/7518/746
Renal failure acuteRenal and urinary disorders0/7518/746
CellulitisInfections and infestations0/7517/746
Acute myocardial infarctionCardiac disorders0/7516/746
Acute respiratory failureRespiratory, thoracic and mediastinal disorders0/7515/746
DyspnoeaRespiratory, thoracic and mediastinal disorders0/7515/746
HypertensionVascular disorders0/7514/746
Most frequent other events
Most frequent other events
EventAcute Phase: ZSExtended Dosing Phase: ZS
HypertensionVascular disorders1/75178/746
Oedema peripheralGeneral disorders1/75172/746
NauseaGastrointestinal disorders4/75156/746
Urinary tract infectionInfections and infestations3/75155/746
ConstipationGastrointestinal disorders2/75146/746
AnaemiaBlood and lymphatic system disorders0/75142/746
Upper respiratory infectionInfections and infestations0/75137/746

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Acute Phase: ZS
Mean63.6 ± 13.03
Sex: Female, Male
Sex: Female, Male(Participants)Acute Phase: ZS
Female303
Male448
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Acute Phase: ZS
Asian25
Native Hawaiian or Other Pacific Islander3
Black or African American89
White624
Other10
Use of RAAS inhibitor medication
Use of RAAS inhibitor medication(Participants)Acute Phase: ZS
Count of participants527
Co-morbidities at baseline
Co-morbidities at baseline(Participants)Acute Phase: ZS
Diabetes mellitus471
Chronic kidney disease513
Heart Failure285
Baseline eGFR
Baseline eGFR(Participants)Acute Phase: ZS
<1546
15-<30243
30-<60263
≥60190
Missing9
Acute Phase baseline Serum Potassium
Acute Phase baseline Serum Potassium(Participants)Acute Phase: ZS
<5.5 mmol/L287
5.5<6.0 mmol/L338
≥6.0 mmol/L126
08

Study locations

51 sites
  • Scottsboro, Alabama 35768, United States
  • Tempe, Arizona 85284, United States
  • Tucson, Arizona 85724, United States
  • Chula Vista, California 90717, United States
  • Los Angeles, California 90022, United States
  • Paramount, California 90723, United States
  • Riverside, California 92505, United States
  • Sacramento, California 95825, United States
  • Whittier, California 90603, United States
  • Denver, Colorado 80230, United States
  • Brandon, Florida 33511, United States
  • DeLand, Florida 32720, United States
  • Hudson, Florida 34667, United States
  • Lauderdale Lakes, Florida 33313, United States
  • Miami Lakes, Florida 33018, United States
  • Miami, Florida 33015, United States
  • Miami, Florida 33125, United States
  • New Smyrna Beach, Florida 32168, United States
  • New Smyrna, Florida 32168, United States
  • Tampa, Florida 33614, United States
  • Winter Park, Florida 32789, United States
  • Columbus, Georgia 31901, United States
  • Evergreen Park, Illinois 60805, United States
  • Joliet, Illinois 60435, United States
  • Paducah, Kentucky 42003, United States
  • Shreveport, Louisiana 71101, United States
  • Chesterfield, Michigan 48047, United States
  • Kansas City, Missouri 64411, United States
  • Saint Louis, Missouri 63110, United States
  • Great Neck, New York 11021, United States
  • Providence, Rhode Island 02903, United States
  • Orangeburg, South Carolina 29118, United States
  • Sumter, South Carolina 29150, United States
  • Chattanooga, Tennessee 37408, United States
  • San Antonio, Texas 78215, United States
  • San Antonio, Texas 78229, United States
  • Saint George, Utah 84770, United States
  • Gosford, New South Wales 2250, Australia
  • Woolloongabba, Queensland 4102, Australia
  • Heidelberg, Victoria 3084, Australia
  • Melbourne, Victoria 3073, Australia
  • Parkville, Victoria 3050, Australia
  • Berlin, 13353, Germany
  • Stuttgart, 70376, Germany
  • Amsterdam, 1105 AZ, Netherlands
  • Lasi, 700503, Romania
  • Cape Town, 7925, South Africa
  • Meyerspark, South Africa
  • Port Elizabeth, 6001, South Africa
  • Somerset West, 7130, South Africa
  • Leicester, LE1 9HN, United Kingdom
09

References and documents

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 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 27, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02163499
Lead sponsor
ZS Pharma, Inc.
Responsible party
Sponsor
First posted
Jun 13, 2014
Start date
Jun 30, 2014
Primary completion
Nov 30, 2016
Completion
Nov 30, 2016
Results posted
Jun 27, 2018
Last update
Jun 27, 2018

Study contacts

Henrik Rasmussen, MD, PhD
study chair · ZS Pharma, Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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