Phase 3
Completed N=258
Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.
Source: ClinicalTrials.gov NCT02088073 ↗Enrolled (actual)
258
Serious AEs
2.0%
Results posted
Dec 2018
Primary outcomePrimary: Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population). — 5.0603; 4.7544; 4.5081; 4.3742 mmol/L
◆ Published Evidence
Highly cited
403citations · ~34 / year
Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical 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 phase versus no difference between each ZS dose (highest to lowest) versus placebo control (null hypothesis).
Linked Publications (3)
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Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial.
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Potassium binders for chronic hyperkalaemia in people with chronic kidney disease.
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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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population). |
5.0603; 4.7544; 4.5081; 4.3742 | — |
| SECONDARY The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT). |
7.4; 13.4; 13.9; 16.8 | — |
| SECONDARY Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . |
5.55; 5.53; 5.58; 5.55; -0.86; -1.03 | — |
| SECONDARY Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . |
-15.11; -18.53; -22.19; -20.04; -8.45; -12.84 | — |
| SECONDARY Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. |
4.55; 4.51; 4.38; 4.45; 0.13; -0.01 | — |
| SECONDARY Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. |
3.39; 0.06; -0.51; -0.20; 11.64; 6.93 | — |
| SECONDARY Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L) |
7; 14; NA; NA | — |
| SECONDARY Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8 |
0.06392; 0.06367; 0.07708; 0.06849 | — |
| SECONDARY Proportion of Subjects Who Remained Normokalemic During Maintenance Phase |
0.866; 0.933; 0.920; 0.926; 0.84; 0.933 | — |
| SECONDARY Median Time to Relapse in S-K Values |
19; 29; NA; NA | — |
| SECONDARY Exponential Rate of Change in S-K Values During the Acute Phase at 24 Hours and 48 Hours of Study Drug Treatment. |
-0.00373; -0.00324 | — |
| SECONDARY Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. |
5.55; -0.23; -0.41; -0.51; -0.68; -0.75 | — |
| SECONDARY Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. |
-3.91; -7.13; -9.00; -12.03; -13.41; -18.56 | — |
| SECONDARY Proportion of Subjects Who Achieve Normokalemia During the Acute Phase at 24 and 48 Hours After Start of Dosing |
0.661; 0.88 | — |
| SECONDARY Median Time to Normalization (3.50-5.0 mmol/L) in S-K Levels in the 48 Hours of Initial Treatment |
2.17 | — |
Eligibility Criteria
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.
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.
Data sourced from ClinicalTrials.gov (NCT02088073) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.