HyperkalemiaPhase 3HARMONIZE AsiaNCT03528681
A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia.
A Phase 3 study testing Sodium Zirconium Cyclosilicate 5g and Sodium Zirconium Cyclosilicate 10g in people with Hyperkalemia, run by AstraZeneca at 66 sites in 2 countries.
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). Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Hyperkalemia
- What is being tested?
- Sodium Zirconium Cyclosilicate 5g and Sodium Zirconium Cyclosilicate 10g
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 270 participants
- Where
- 66 sitesin 2 countries
- Study dates
- 6 May 2021to 15 Sep 2022
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
- QTc(f) > 550 msec
- Patients on dialysis
- Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of ZS
- Patients who need hospitalization after taking blood samples on day 1 of the open-label initial phase
Trial locations and contacts
66 sites in 2 countries.
66 sites in 2 countries
China52 sites
Research Site
Baotou, 14010
Research Site
Beijing, 100029
Research Site
Beijing, 100144
Research Site
Beijing, 100853
Research Site
Beijing, 102206
Research Site
Bengbu, 233004
Research Site
Changchun, 130021
Research Site
Changsha, 410008
Research Site
Changsha, 430033
Research Site
Chengdu, 610041
Research Site
Chengdu, 610072
Research Site
Dalian, 116027
Research Site
Dongguan, 523009
Research Site
Fuzhou, 350005
Research Site
Fuzhou, 350025
Research Site
Guangzhou, 510080
Research Site
Guangzhou, 510120
Research Site
Guiyang, 550004
Research Site
Haikou, 570311
Research Site
Hangzhou, 310003
Research Site
Hangzhou, 310009
Research Site
Hefei, 230022
Research Site
Hefei, 230601
Research Site
Jilin City, 132011
Research Site
Jinan, 250021
Research Site
Jingzhou, 434020
Research Site
Kunming, 650011
Research Site
Kunming, 650021
Research Site
Lanzhou, 730030
Research Site
Nanchang, 330006
Research Site
Ningbo, 315010
Research Site
Qingdao, 266000
Research Site
Shanghai, 200025
Research Site
Shanghai, 200090
Research Site
Shanghai, 200127
Research Site
Suzhou, 215006
Research Site
Taiyuan, 030001
Research Site
Taiyuan, 030012
Research Site
Tianjin, 300121
Research Site
Tianjin, 300211
Research Site
Wuhan, 430030
Research Site
Wuhan, 430070
Research Site
Wuxi, 214023
Research Site
Xi'an, 710061
Research Site
Xiamen, 361003
Research Site
Xining, 810001
Research Site
Xining, 810007
Research Site
Yangzhou, 225001
Research Site
Yichang, 443003
Research Site
Yinchuan, 750004
Research Site
Zhanjiang, 524001
Research Site
Zhuzhou, 412007
India14 sites
Research Site
Ahmedabad, 380006
Research Site
Ahmedabad, 380015
Research Site
Ahmedabad, 380016
Research Site
Bangalore, 560002
Research Site
Bangalore, 560004
Research Site
Bengaluru, 560004
Research Site
Chandigarh, 160030
Research Site
Chennai, 600001
Research Site
Hyderabad, 500018
Research Site
Kolkata, 700054
Research Site
Nagpur, 440012
Research Site
New Delhi, 110002
Research Site
New Delhi, 110017
Research Site
Vijayawada, 522002
About this study
Official title: 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
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).
Read the detailed 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.
- Conditions
- Hyperkalemia
- Being tested
- Sodium Zirconium Cyclosilicate 5g, Sodium Zirconium Cyclosilicate 10g, Placebo
- Medical subject headings
- Hyperkalemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Sodium Zirconium Cyclosilicate 10g | Experimental | Suspension administered 10g orally once daily for 28 days after the open label initial phase. Receives: Drug: Sodium Zirconium Cyclosilicate 10g |
| Sodium Zirconium Cyclosilicate 5g | Experimental | Suspension administered 5g orally once daily for 28 days after the open label initial phase. Receives: Drug: Sodium Zirconium Cyclosilicate 5g |
| Matching Placebo | Placebo comparator | Suspension administered orally placebo once daily for 28 days after the open label initial phase. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through open label initial phase
Proportion of Patients Who Remain Normokalemic During RTP
Proportion of patients who remain normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) during RTP (Day 8 to Day 29). The results in the table below are presented for RTP.
Measured: Through 28-day randomized treatment study phase day 8-29
Proportion of Normokalemic Patients at the End of RTP
Proportion of normokalemic patients (as defined by S-K between 3.5-5.0 mmol/l, inclusive). The results in the table below are presented for RTP.
Measured: The end of 28-day randomized treatment study phase
Days Patients Remain Normokalemic
The number of days patients remain normokalemic during days 8-29 of the randomized treatment study phase. The results in the table below are presented for RTP.
Measured: Through days 8-29 of the randomized treatment phase.
Mean Change in S-K Levels
The mean change in S-K levels evaluated relative to the RTP baseline. The results in the table below are presented for RTP.
Measured: Through 28-day randomized treatment phase.
Mean Percent Change in S-K Levels
The mean percent change in S-K levels evaluated relative to the RTP baseline. The results in the table below are presented for RTP.
Measured: Through 28-day randomized treatment phase.
Least Square Mean Changes in S-Aldo and P-Renin Levels
Comparison between placebo and each SZC treatment group (high to low) with regard to the mean S-Aldo and P-Renin levels during the randomized treatment phase days 15-29.
Measured: Through 28 day randomized treatment study phase day 15-29
Hyperkalaemia at Day 29
The number of patients with hyperkalaemia at day 29. The results in the table below are presented for RTP.
Measured: Day 29
Percentage of Patients Without Hyperkalemia
Kaplan-Meier estimate at Day 29 of percentage of patients without hyperkalemia. The results in the table below are presented for RTP.
Measured: Day 29 of randomized treatment phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2018
- Study start6 May 2021
- Primary completion15 Sep 2022
- Study completion15 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperkalemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 270 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03528681
- Sponsor's protocol ID
- D9480C00001
- Acronym
- HARMONIZE Asia
- Status last verified
- May 2025
- First submitted
- 16 Apr 2018
- Last updated
- 14 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39112102