Phase 3
N=267
A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia
Hyperkalemia
Bottom Line
View on ClinicalTrials.gov: NCT02875834 ↗Enrolled (actual)
267
Serious AEs
1.6%
Results posted
Aug 2020
Primary outcome: Primary: Least Square Mean S-K Level on Days 8-29 — 4.811; 4.381; 5.321 mmol/L — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sodium Zirconium Cyclosilicate (ZS) 10g (Drug); Sodium Zirconium Cyclosilicate (ZS) 5g (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- Feb 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Least Square Mean S-K Level on Days 8-29 |
4.811; 4.381; 5.321 | <0.001 sig |
| SECONDARY Proportion of Patients Achieving Normokalemia |
169; 93; 5; 238; 22; 7 | — |
| SECONDARY Exponential Rate of Change in S-K Levels |
-0.004 | — |
| SECONDARY Absolute Change From Baseline in S-K Levels |
-0.19; -0.48; -0.57; -0.81; -0.91; -1.28 | — |
| SECONDARY Percentage Change From Baseline in S-K Levels |
-3.26; -8.29; -9.88; -14.08; -15.84; -22.16 | — |
| SECONDARY Proportion of Patients Remaining Normokalemic |
58; 75; 12 | <0.001 sig |
| SECONDARY Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit |
93; 94; 45; 89; 93; 40 | — |
| SECONDARY Days Patients Remain Normokalemic |
10.810; 15.623; 3.543 | <0.001 sig |
| SECONDARY Mean Change in S-K Levels |
0.03; -0.09; 0.17; 0.23; -0.08; 0.60 | — |
| SECONDARY Mean Percentage Change in S-K Levels |
1.00; -1.74; 4.19; 5.51; -1.52; 14.19 | — |
| SECONDARY Number of Hyperkalemic Patients |
66; 45; 47 | <0.001 sig |
| SECONDARY Mean Changes in S-Aldosterone and P Renin Levels |
-112.69; -85.63; -98.54; -91.75; -96.37; 39.78 | — |
| SECONDARY Patient Reported Health State (EQ-5D) Questionnaire |
75.0; 74.3; 72.7; 77.6; 76.9; 76.6 | — |
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 two days of initial ZS therapy (10g TID).
Eligibility Criteria
Inclusion Criteria
- Provision of informed consent prior to any study specific procedures
- Female and male patients aged ≥18 and ≤ 90 years
- 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 48-hour 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 and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy.
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
- Pseudohyperkalemia signs and symptoms
- 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
- 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
- Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
- Patients with cardiac arrhythmias that require immediate treatment
- 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
Data sourced from ClinicalTrials.gov (NCT02875834). 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.