A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia.
HARMONIZE Asia
A Phase 3 Multicenter, Prospective, Randomized, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of ZS (Sodium Zirconium Cyclosilicate), in Patients With Hyperkalemia-HARMONIZE Asia
1 other identifier
interventional
270
2 countries
66
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2021
66 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 16, 2018
CompletedFirst Posted
Study publicly available on registry
May 18, 2018
CompletedStudy Start
First participant enrolled
May 6, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 15, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
September 15, 2022
CompletedResults Posted
Study results publicly available
May 14, 2025
CompletedMay 14, 2025
May 1, 2025
1.4 years
April 16, 2018
September 14, 2023
May 13, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
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.
Days 8 to 29 (Randomized treatment study phase) used for model-based least squares mean computation
Secondary Outcomes (12)
Percentage of Patients Who Achieve Normokalemia
Through open label initial phase
Exponential Rate of Change in S-K Levels
Through 24 hours post-dose in the initial phase
Absolute Change From Baseline in S-K Levels
Through open label initial phase
Percentage Change From Baseline in S-K Levels
Through open label initial phase
Proportion of Patients Who Remain Normokalemic During RTP
Through 28-day randomized treatment study phase day 8-29
- +7 more secondary outcomes
Study Arms (3)
Sodium Zirconium Cyclosilicate 10g
EXPERIMENTALSuspension administered 10g orally once daily for 28 days after the open label initial phase.
Sodium Zirconium Cyclosilicate 5g
EXPERIMENTALSuspension administered 5g orally once daily for 28 days after the open label initial phase.
Matching Placebo
PLACEBO COMPARATORSuspension administered orally placebo once daily for 28 days after the open label initial phase.
Interventions
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.
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.
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 Criteria
You may qualify if:
- Provision of informed consent (pre-screening consent) prior to any study specific procedures
- Female and male patients aged ≥18 and ≤ 90 years
- Provision of informed consent prior to any study specific procedures
- 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
- 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 (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
You may not qualify if:
- Involvement in the planning and/or conduct of the study
- Participation in another clinical study with an investigational product during the last 3 months
- 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
- 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
- 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
- Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
- Patients with cardiac arrhythmias that require immediate treatment
- History of QT prolongation associated with other medications that required discontinuation of that medication.
- Congenital long QT syndrome
- Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (66)
Research Site
Baotou, 14010, China
Research Site
Beijing, 100029, China
Research Site
Beijing, 100144, China
Research Site
Beijing, 100853, China
Research Site
Beijing, 102206, China
Research Site
Bengbu, 233004, China
Research Site
Changchun, 130021, China
Research Site
Changsha, 410008, China
Research Site
Changsha, 430033, China
Research Site
Chengdu, 610041, China
Research Site
Chengdu, 610072, China
Research Site
Dalian, 116027, China
Research Site
Dongguan, 523009, China
Research Site
Fuzhou, 350005, China
Research Site
Fuzhou, 350025, China
Research Site
Guangzhou, 510080, China
Research Site
Guangzhou, 510120, China
Research Site
Guiyang, 550004, China
Research Site
Haikou, 570311, China
Research Site
Hangzhou, 310003, China
Research Site
Hangzhou, 310009, China
Research Site
Hefei, 230022, China
Research Site
Hefei, 230601, China
Research Site
Jilin, 132011, China
Research Site
Jinan, 250021, China
Research Site
Jingzhou, 434020, China
Research Site
Kunming, 650011, China
Research Site
Kunming, 650021, China
Research Site
Lanzhou, 730030, China
Research Site
Nanchang, 330006, China
Research Site
Ningbo, 315010, China
Research Site
Qingdao, 266000, China
Research Site
Shanghai, 200025, China
Research Site
Shanghai, 200090, China
Research Site
Shanghai, 200127, China
Research Site
Suzhou, 215006, China
Research Site
Taiyuan, 030001, China
Research Site
Taiyuan, 030012, China
Research Site
Tianjin, 300121, China
Research Site
Tianjin, 300211, China
Research Site
Wuhan, 430030, China
Research Site
Wuhan, 430070, China
Research Site
Wuxi, 214023, China
Research Site
Xi'an, 710061, China
Research Site
Xiamen, 361003, China
Research Site
Xining, 810001, China
Research Site
Xining, 810007, China
Research Site
Yangzhou, 225001, China
Research Site
Yichang, 443003, China
Research Site
Yinchuan, 750004, China
Research Site
Zhanjiang, 524001, China
Research Site
Zhuzhou, 412007, China
Research Site
Ahmedabad, 380006, India
Research Site
Ahmedabad, 380015, India
Research Site
Ahmedabad, 380016, India
Research Site
Bangalore, 560002, India
Research Site
Bangalore, 560004, India
Research Site
Bengaluru, 560004, India
Research Site
Chandigarh, 160030, India
Research Site
Chennai, 600001, India
Research Site
Hyderabad, 500018, India
Research Site
Kolkata, 700054, India
Research Site
Nagpur, 440012, India
Research Site
New Delhi, 110002, India
Research Site
New Delhi, 110017, India
Research Site
Vijayawada, 522002, India
Related Publications (1)
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.
PMID: 39112102DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca Clinical Study Information Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 16, 2018
First Posted
May 18, 2018
Study Start
May 6, 2021
Primary Completion
September 15, 2022
Study Completion
September 15, 2022
Last Updated
May 14, 2025
Results First Posted
May 14, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.