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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03528681
Other study ID # D9480C00001
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date May 6, 2021
Est. completion date September 15, 2022

Study information

Verified date October 2022
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 250
Est. completion date September 15, 2022
Est. primary completion date September 15, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 90 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Sodium Zirconium Cyclosilicate 5g
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 10g
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.
Placebo
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.

Locations

Country Name City State
China Research Site Beijing
China Research Site Beijing
China Research Site Beijing
China Research Site Changsha
China Research Site Chengdu
China Research Site Chengdu
China Research Site Dongguan
China Research Site Fuzhou
China Research Site Guangzhou
China Research Site Guangzhou
China Research Site Guiyang
China Research Site Hefei
China Research Site Jingzhou
China Research Site Kunming
China Research Site Lanzhou
China Research Site Nanchang
China Research Site Shanghai
China Research Site Shanghai
China Research Site Shanghai
China Research Site Suzhou
China Research Site Taiyuan
China Research Site Taiyuan
China Research Site Tianjin
China Research Site Tianjin
China Research Site Wuhan
China Research Site Xian
China Research Site Xining
China Research Site Yangzhou
China Research Site Yichang
China Research Site Yinchuan
China Research Site Zhanjiang
China Research Site Zhuzhou

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Other Vital signs Vital signs include pulse rate and blood pressure Throughout the study, from the time of signature of the main study informed consent form up to study completion.
Other ECG measurements ECG measurements include heart rate, P and QRS durations, PR and QTc(f) intervals. Collected from standard lead of the computerized quantitative 12- lead ECG. Throughout the study, from the time of signature of the main study informed consent form up to study completion.
Other AEs, including SAEs The evaluation of AE will include, but not be limited to, a classification by SOC/PT, an assessment of severity and causality with regards to the IP, as well as action taken as the response to the AE, e.g. IP discontinuation Throughout the study, from the time of signature of the main study informed consent form up to study completion.
Other Safety laboratory evaluations, including determination of hypokalaemia Include, but are not limited to, serum potassium, calcium, magnesium, sodium, phosphate, bicarbonate, as well as blood urea nitrogen. Throughout the study, from the time of signature of the main study informed consent form up to study completion.
Primary Least Squares Means of S-K values during the 28-day randomized treatment study phase Study Days 8-29. Comparison between placebo and each ZS treatment group (high to low) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29 Through 28 day randomized treatment study phase day 8-29
Secondary Exponential rate of change in S-K levels Exponential rate of change in S-K levels (blood) during the open label initial phase Through open label initial phase
Secondary Mean change from baseline in S-K levels Mean Change (absolute and percent change) from baseline in S-K levels (blood) at all measured time intervals post dose in the open label initial phase Through open label initial phase
Secondary proportion of patients achieve normokalemia Proportion of patients who achieve normokalemia during the open label initial phase at 24 hours and at the end of the open label phase Through open label initial phase
Secondary Time to normalization in S-K levels Time to normalization in S-K levels (normalization defined as S-K levels between 3.5-5.0 mmol/L, inclusive) in the open label initial phase Through open label initial phase
Secondary Proportion of patients remaining normokalemic The proportion of patients who remain normokalemic (as defined by S-K between 3.5-5.0 mmol/L, inclusive) at the end of the 28-day randomized treatment study phase and during the 28-day randomized treatment study phase Through 28-day randomized treatment study phase
Secondary Mean number of Days patients remain normokalemic The mean number of days patients remain normokalemic during the 28-day randomized treatment study phase Through 28-day randomized treatment study phase
Secondary Mean change and mean percent change in S-K levels The mean change and mean percent change in S-K levels evaluated relative to both baselines Through 28-day randomized treatment study phase
Secondary Time to hyperkalemia The time to hyperkalemia (defined as S-K =5.1mmol/L) Through 28-day randomized treatment study phase
Secondary Mean changes in S-Aldo and P-Renin levels The mean changes in S-Aldo and P-Renin levels Through 28-day randomized treatment study phase
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