Phase 3
N=270
A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia.
Hyperkalemia
Bottom Line
View on ClinicalTrials.gov: NCT03528681 ↗Enrolled (actual)
270
Serious AEs
2.1%
Results posted
May 2025
Primary outcome: Primary: Least Square Mean S-K Level on Days 8-29 — 4.859; 4.440; 5.225 mmol/L — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sodium Zirconium Cyclosilicate 5g (Drug); Sodium Zirconium Cyclosilicate 10g (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Least Square Mean S-K Level on Days 8-29 |
4.859; 4.440; 5.225 | <0.001 sig |
| SECONDARY Percentage of Patients Who Achieve Normokalemia |
180; 228 | — |
| SECONDARY Exponential Rate of Change in S-K Levels |
-0.0051 | — |
| SECONDARY Absolute Change From Baseline in S-K Levels |
-0.936; -1.107 | — |
| SECONDARY Percentage Change From Baseline in S-K Levels |
-15.880; -18.588 | — |
| SECONDARY Proportion of Patients Who Remain Normokalemic During RTP |
0.596; 0.818; 0.279 | <0.001 sig |
| SECONDARY Proportion of Normokalemic Patients at the End of RTP |
47; 65; 14 | 0.035 sig |
| SECONDARY Days Patients Remain Normokalemic |
9.11; 14.54; 3.40 | <0.001 sig |
| SECONDARY Mean Change in S-K Levels |
-0.04; -0.15; 0.02; 0.09; -0.27; 0.40 | — |
| SECONDARY Mean Percent Change in S-K Levels |
-0.81; -3.13; 0.41; 2.10; -5.57; 8.56 | — |
| SECONDARY Least Square Mean Changes in S-Aldo and P-Renin Levels |
-21.926; -53.945; 83.322; -0.348; -0.424; -0.362 | <0.001 sig |
| SECONDARY Hyperkalaemia at Day 29 |
77; 50; 48 | — |
| SECONDARY Percentage of Patients Without Hyperkalemia |
20.3; 47.1; 4.0 | <0.001 sig |
Summary
To evaluate the efficacy of two different doses (5 and 10 g) of ZS orally administered once daily (qd) vs placebo in maintaining normokalemia in initially hyperkalemic patients having achieved normokalemia following 24 or 48 hours of initial ZS therapy (10g TID).
Eligibility Criteria
Inclusion Criteria
- Provision of informed consent (pre-screening consent) prior to any study specific procedures
- Female and male patients aged ≥18 and ≤ 90 years
- Provision of informed consent prior to any study specific procedures
- Two consecutive i-STAT potassium values, measured 60 minutes (± 10 minutes) apart, both ≥ 5.1 mmol/L and measured within 1 day of the first ZS dose on open-label initial phase Day 1
- Ability to have repeated blood draws or effective venous catheterization
- Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study (from the time they sign consent) and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used
Exclusion Criteria
- Involvement in the planning and/or conduct of the study
- Participation in another clinical study with an investigational product during the last 3 months
- Presence of any condition which, in the opinion of the investigator, places the patient at undue risk or potentially jeopardizes the quality of the data to be generated
- Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to excessive fist clenching to make veins prominent, difficult or traumatic venepuncture, or history of severe leukocytosis or thrombocytosis
- Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug
- Patients treated with resins, calcium acetate,calcium carbonate, or lanthanum carbonate,within 7 days prior to the first dose of study drug
- Patients with a life expectancy of less than 3 months
- Patients 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
- Female patients who are pregnant, lactating, or planning to become pregnant
- Patients with diabetic ketoacidosis
- Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
- Patients with cardiac arrhythmias that require immediate treatment
- History of QT prolongation associated with other medications that required discontinuation of that medication.
- Congenital long QT syndrome
- Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
- QTc(f) > 550 msec
- Patients on dialysis
- Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of ZS
- Patients who need hospitalization after taking blood samples on day 1 of the open-label initial phase
Data sourced from ClinicalTrials.gov (NCT03528681). 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.