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

NCT ID: NCT03528681

Last Updated: 2025-05-14

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

270 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-06

Study Completion Date

2022-09-15

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Hyperkalemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Sodium Zirconium Cyclosilicate 10g

Suspension administered 10g orally once daily for 28 days after the open label initial phase.

Group Type EXPERIMENTAL

Sodium Zirconium Cyclosilicate 10g

Intervention Type DRUG

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.

Sodium Zirconium Cyclosilicate 5g

Suspension administered 5g orally once daily for 28 days after the open label initial phase.

Group Type EXPERIMENTAL

Sodium Zirconium Cyclosilicate 5g

Intervention Type DRUG

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.

Matching Placebo

Suspension administered orally placebo once daily for 28 days after the open label initial phase.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Baotou, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Beijing, , China

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Bengbu, , China

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Changchun, , China

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Changsha, , China

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Changsha, , China

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Chengdu, , China

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Chengdu, , China

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Dalian, , China

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Dongguan, , China

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Fuzhou, , China

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Fuzhou, , China

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Guangzhou, , China

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Guangzhou, , China

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Guiyang, , China

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Haikou, , China

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Hangzhou, , China

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Hangzhou, , China

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Hefei, , China

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Hefei, , China

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Jilin, , China

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Jinan, , China

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Jingzhou, , China

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Kunming, , China

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Kunming, , China

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Lanzhou, , China

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Nanchang, , China

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Ningbo, , China

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Qingdao, , China

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Shanghai, , China

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Shanghai, , China

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Shanghai, , China

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Suzhou, , China

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Taiyuan, , China

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Taiyuan, , China

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Tianjin, , China

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Tianjin, , China

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Wuhan, , China

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Wuhan, , China

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Wuxi, , China

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Xi'an, , China

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Xiamen, , China

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Xining, , China

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Xining, , China

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Yangzhou, , China

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Yichang, , China

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Yinchuan, , China

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Zhanjiang, , China

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Zhuzhou, , China

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Ahmedabad, , India

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Ahmedabad, , India

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Ahmedabad, , India

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Bangalore, , India

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Bangalore, , India

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Bengaluru, , India

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Chandigarh, , India

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Chennai, , India

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Hyderabad, , India

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Kolkata, , India

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Nagpur, , India

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New Delhi, , India

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New Delhi, , India

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Vijayawada, , India

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Countries

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China India

References

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Liang X, Lu W, Yu X, Cheng H, He Q, Peng Q, Ni Z, Long G, Wang L, Chen W, Li R, Zhao J, Zhang Y, Lisovskaja V, Tang Z. HARMONIZE Asia: A Phase III Randomized Study to Investigate the Efficacy and Safety of Sodium Zirconium Cyclosilicate in Patients with Hyperkalemia in China. Clin Ther. 2024 Sep;46(9):702-710. doi: 10.1016/j.clinthera.2024.07.004. Epub 2024 Aug 6.

Reference Type DERIVED
PMID: 39112102 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D9480C00001

Identifier Type: -

Identifier Source: org_study_id

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