Phase 3
N=103
ZS Ph2/3 Dose-response Study in Japan
Hyperkalemia
Bottom Line
View on ClinicalTrials.gov: NCT03127644 ↗Enrolled (actual)
103
Serious AEs
0.0%
Results posted
May 2019
Primary outcome: Primary: Exponential Rate of Change in Serum Potassium (S-K) Values During the Initial 48 Hours of Study Drug Treatment — -0.00273; -0.00508; -0.00012 log (mmol/L) / hour — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sodium Zirconium Cyclosilicate (ZS) 5g (Drug); Sodium Zirconium Cyclosilicate (ZS) 10g (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- Feb 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Exponential Rate of Change in Serum Potassium (S-K) Values During the Initial 48 Hours of Study Drug Treatment |
-0.00273; -0.00508; -0.00012 | <0.0001 sig |
| SECONDARY Percentage of Patients Who Achieved Normokalaemia at 48 Hours |
85.3; 91.7; 15.2 | <0.0001 sig |
| SECONDARY Exponential Rate of Change in S-K Values During the Initial 24 Hours of Study Drug Treatment |
-0.00234; -0.00403; -0.00002 | 0.0004 sig |
| SECONDARY Percentage of Patients Who Achieved Normokalaemia at 24 Hours |
35.3; 83.3; 27.3 | 0.6167 |
| SECONDARY Percentage of Patients Who Achieved Normokalaemia at Each Scheduled Potassium Assessment Time Point |
2.9; 5.6; 0.0; 29.4; 47.2; 21.2 | — |
| SECONDARY Mean Change From Baseline in S-K Values at All Measured Time Intervals |
-0.20; -0.37; -0.13; -0.41; -0.50; -0.33 | — |
| SECONDARY Mean Percent Change From Baseline in S-K Values at All Measured Time Intervals |
-3.61; -6.72; -2.32; -7.46; -9.07; -6.06 | — |
| SECONDARY Time to Normalisation in S-K Values |
3.883; 1.758; 3.867 | 0.0586 |
| SECONDARY Time to a Decrease in S-K Levels of 0.5 mmol/L |
3.883; 2.892; 4.050 | 0.0250 sig |
Summary
To assess efficacy of 5 g three times daily (TID) and 10 g TID ZS versus placebo in Japanese patients with hyperkalemia (serum potassium [S-K] ≥ 5.1 mmol/L and ≤ 6.5 mmol/L).
Eligibility Criteria
Inclusion Criteria
- Provision of informed consent prior to any study specific procedures.
- Patients aged ≥18. For patients aged <20 years, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
- Two consecutive i-STAT potassium values, measured 60 (± 10) minutes apart, both values should be ≥ 5.1 mmol/L and ≤ 6.5 mmol/L and measured within 1 day before the first dose of study drug on Study 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 (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) 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 (applies to both AstraZeneca staff and/or staff at the study site)
- Cause or symptoms of pseudohyperkalemia, such as
- hemolyzed blood specimen due to excessive fist clenching to make veins prominent
- hemolyzed blood specimen due to difficult or traumatic venepuncture
- history of severe leukocytosis or thrombocytosis
- Patients treated with lactulose, rifaximin, or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of study drug on Study Day 1
- Patients treated with resins (such as sevelamer hydrochloride, sodium polystyrene sulfonate [SPS; e.g. Kayexalate®] or calcium polystyrene sulfonate [CPS]), 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 patients' tasks associated with the protocol
- Female patients who are pregnant, lactating, or planning to become pregnant
- Patients who have an active or history of 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
- Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry
- Patients with cardiac arrhythmias that require immediate treatment
- Patients on dialysis
Data sourced from ClinicalTrials.gov (NCT03127644). 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.