A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia.

AstraZeneca270 enrolled

Overview

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).

This study will be conducted in approximately 35 centers in China. Before patients are randomized to the double-blind phase, they will receive open-label ZS for 24 or 48 hours during the initial phase. It is expected that approximately 490 patients will need to be enrolled, to have approximately 280 patients entered into the open-label initial phase resulting in 250 patients being randomized in the 28-day treatment study phase. Enrolment will be stopped when 250 patients have been initiated with the 28-day randomized treatment study phase.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

270

Conditions

Hyperkalemia

Interventions

Sodium Zirconium Cyclosilicate 5gDRUG

Suspension administered Sodium Zirconium Cyclosilicate 5g orally once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days.

Sodium Zirconium Cyclosilicate 10gDRUG

Suspension administered Sodium Zirconium Cyclosilicate 10g orally once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days.

PlaceboDRUG

Suspension administered orally placebo once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Provision of informed consent (pre-screening consent) prior to any study specific procedures 2. Female and male patients aged ≥18 and ≤ 90 years 3. Provision of informed consent prior to any study specific procedures 4. 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 5. Ability to have repeated blood draws or effective venous catheterization 6. 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: 1. Involvement in the planning and/or conduct of the study 2. Participation in another clinical study with an investigational product during the last 3 months 3. 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 4. 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 5. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug 6. Patients treated with resins,calcium acetate,calcium carbonate, or lanthanum carbonate,within 7 days prior to the first dose of study drug 7. Patients with a life expectancy of less than 3 months 8. 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 9. Female patients who are pregnant, lactating, or planning to become pregnant 10. Patients with diabetic ketoacidosis 11. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof 12. Patients with cardiac arrhythmias that require immediate treatment 13. History of QT prolongation associated with other medications that required discontinuation of that medication. 14. Congenital long QT syndrome 15. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted 16. QTc(f) \> 550 msec 17. Patients on dialysis 18. Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of ZS 19. Patients who need hospitalization after taking blood samples on day 1 of the open-label initial phase

Locations (66)

Outcomes

Primary Outcomes

Least Square Mean S-K Level on Days 8-29

Comparison between placebo and each SZC treatment group (high to low) with regard to the mean S-K level during the randomized treatment phase days 8-29. Mixed-effects models were used to estimate least-squares means.

Time frame: Days 8 to 29 (Randomized treatment study phase) used for model-based least squares mean computation

Secondary Outcomes

Percentage of Patients Who Achieve Normokalemia

Percentage of patients who achieve normokalemia during the open label initial phase at 24 hours and at the end of the open label phase. End of OLP is defined as Day 2 (24 hours post first dose) or Day 3 (48 hours post first dose) depending on when the subject achieved normokalemia based on the pre-dose i-STAT potassium level. The results in the table below are presented for OLP.

Time frame: Through open label initial phase

Exponential Rate of Change in S-K Levels

Exponential rate of change in S-K levels (blood) during the open-label initial phase 24 hours post-dose. Least Square Mean corresponds to the exponential rate of change i.e. the slope (for time) in terms of log-transformed S-K levels. The results in the table below are presented for OLP.

Time frame: Through 24 hours post-dose in the initial phase

Absolute Change From Baseline in S-K Levels

Absolute change from baseline in S-K levels at all measured time intervals. End of OLP is defined as Day 2 (24 hours post first dose) or Day 3 (48 hours post first dose) depending on when the subject achieved normokalemia based on the pre-dose i-STAT potassium level. The results in the table below are presented for OLP.

Time frame: Through open label initial phase

Percentage Change From Baseline in S-K Levels

Percentage change from baseline in S-K levels at all measured time intervals. End of OLP is defined as Day 2 (24 hours post first dose) or Day 3 (48 hours post first dose) depending on when the subject achieved normokalemia based on the pre-dose i-STAT potassium level. The results in the table below are presented for OLP.

Data from ClinicalTrials.gov

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