Clinical Trials List
Protocol NumberD9480C00002
NCT Number(ClinicalTrials.gov Identfier)NCT02875834
2015-01-01 - 2020-06-30
Phase III
Terminated7
ICD-10E87.5
Hyperkalemia
ICD-9276.7
Hyperpotassemia
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 Global
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Trial Applicant
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Sponsor
AstraZeneca
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- CHENG-HSU CHEN Division of Nephrology
- 蔡尚峰 Division of Nephrology
- 黃俊德 Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 蔡宏斌 Division of Nephrology
- Jenq-Wen Huang Division of Nephrology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Hyperkalemia
Objectives
1. Primary Objective:
To evaluate the efficacy of two different doses (5 and 10 g) of ZS orally administered once daily (qd) for 28
days in maintaining normokalemia (serum potassium [S-K] between 3.5-5.0 mmol/l, inclusive) in patients
achieving normokalemia following two days of initial phase for patients with hyperkalemia (two consecutive
i-STAT potassium values ≥ 5.1 mmol/l, taken 60 minutes apart) at baseline
2. Secondary Objectives:
To evaluate the proportion of patients who achieve normokalemia after 48 hours of open-label initial
phase treatment with 10g ZS PO three times a day (tid)
48-hour open-label initial phase:
To evaluate the efficacy of ZS in patients with hyperkalemia for the following subgroups:
28-day randomized treatment study phase:
- chronic kidney disease (CKD)
- diabetes mellitus (DM)
- congestive heart failure (CHF)
- those on renin-angiotensin-aldosterone system (RAAS) inhibitors
To evaluate the effect of ZS on serum-Aldosterone (S-Aldo) and plasma-Renin (P-Renin) levels
To evaluate the health state in the study population using EQ-5D
Patient reported outcomes:
3. Safety Objectives:
To evaluate the effect of ZS on other serum electrolytes in both 48-hour openlabel initial phase and 28-day
randomized treatment study phase
To evaluate the safety and tolerability profiles of ZS in both 48-hour openlabel initial phase and 28-day
randomized treatment study phase
Test Drug
ZS
Active Ingredient
Sodium Zirconium Cyclosilicate
Dosage Form
oral
Dosage
5
10
10
Endpoints
1. Primary efficacy variable
The primary efficacy endpoint in this study will be the mean S-K value for 28-day randomized treatment
study phase Study Days 8-29.
2. Secondary efficacy variables
For the 48-hour open-label initial phase, the secondary efficacy endpoints will include the
following parameters:
Exponential rate of change in S-K levels (blood)
Change (absolute and percent (%) change) from baseline in S-K levels at all measured time intervals
post dose
Proportion of patients who achieve normokalemia during the 48-hour open-label initial phase at 24
and 48 hours
Time to normalization in S-K levels (normalization defined as S-K levels between 3.5-5.0 mmol/l,
inclusive)
For the subsequent 28-day randomized treatment study phase, the secondary efficacy
endpoints will include the following parameters:
The proportion of patients who remain normokalemic (as defined by S-K levels between 3.5-5.0
mmol/l, inclusive) at the end of the 28-day randomized treatment study phase and some selected
timepoints during 28-day randomized treatment study phase
The number of days patients remain normokalemic during the 28-day randomized treatment study
phase
The mean change and mean percent change in S-K levels at the selected timepoints evaluated relative
to both 48-hour open-lable initial phase and 28-day randomized treatment study phase baselines
The time to hyperkalemia (defined as S-K ≥5.1 mmol/l)
The mean changes in S-Aldo and P- Renin levels
The primary efficacy endpoint in this study will be the mean S-K value for 28-day randomized treatment
study phase Study Days 8-29.
2. Secondary efficacy variables
For the 48-hour open-label initial phase, the secondary efficacy endpoints will include the
following parameters:
Exponential rate of change in S-K levels (blood)
Change (absolute and percent (%) change) from baseline in S-K levels at all measured time intervals
post dose
Proportion of patients who achieve normokalemia during the 48-hour open-label initial phase at 24
and 48 hours
Time to normalization in S-K levels (normalization defined as S-K levels between 3.5-5.0 mmol/l,
inclusive)
For the subsequent 28-day randomized treatment study phase, the secondary efficacy
endpoints will include the following parameters:
The proportion of patients who remain normokalemic (as defined by S-K levels between 3.5-5.0
mmol/l, inclusive) at the end of the 28-day randomized treatment study phase and some selected
timepoints during 28-day randomized treatment study phase
The number of days patients remain normokalemic during the 28-day randomized treatment study
phase
The mean change and mean percent change in S-K levels at the selected timepoints evaluated relative
to both 48-hour open-lable initial phase and 28-day randomized treatment study phase baselines
The time to hyperkalemia (defined as S-K ≥5.1 mmol/l)
The mean changes in S-Aldo and P- Renin levels
Inclution Criteria
Inclusion criteria
For inclusion in the study patients should fulfil the following criteria:
1. Provision of informed consent prior to any study specific procedures
2. Female and male patients aged ≥18 and ≤ 90 years (≥ 20 in Taiwan)
3. Two consecutive i-STAT potassium values, measured 60-minutes apart, both ≥ 5.1 mmol/l and measured
within 1 day of the first ZS dose on 48-hour open-label initial phase Day 1
4. Ability to have repeated blood draws or effective venous catheterization
5. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of
contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a
spermicide) 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
For inclusion in the study patients should fulfil the following criteria:
1. Provision of informed consent prior to any study specific procedures
2. Female and male patients aged ≥18 and ≤ 90 years (≥ 20 in Taiwan)
3. Two consecutive i-STAT potassium values, measured 60-minutes apart, both ≥ 5.1 mmol/l and measured
within 1 day of the first ZS dose on 48-hour open-label initial phase Day 1
4. Ability to have repeated blood draws or effective venous catheterization
5. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of
contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a
spermicide) 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
Exclusion criteria
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at
the study site)
2. Participation in another clinical study with an investigational product during the last 3 months
3. Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen,
history of severe leukocytosis or thrombocytosis
4. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia
within 7 days prior to the first dose of study drug
5. Patients treated with resins (such as sevelamer acetate or sodium polystyrene sulfonate [SPS; e.g.
Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum carbonate, within 7 days prior to the
first dose of study drug
6. Patients with a life expectancy of less than 3 months
7. 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
8. Female patients who are pregnant, lactating, or planning to become pregnant
9. Patients with diabetic ketoacidosis
10. 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
11. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
12. Patients with cardiac arrhythmias that require immediate treatment
13. Patients on dialysis
14. Patients who are blood donors should not donate blood during the study and for 3 months following their
last dose of ZS
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at
the study site)
2. Participation in another clinical study with an investigational product during the last 3 months
3. Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen,
history of severe leukocytosis or thrombocytosis
4. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia
within 7 days prior to the first dose of study drug
5. Patients treated with resins (such as sevelamer acetate or sodium polystyrene sulfonate [SPS; e.g.
Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum carbonate, within 7 days prior to the
first dose of study drug
6. Patients with a life expectancy of less than 3 months
7. 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
8. Female patients who are pregnant, lactating, or planning to become pregnant
9. Patients with diabetic ketoacidosis
10. 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
11. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
12. Patients with cardiac arrhythmias that require immediate treatment
13. Patients on dialysis
14. Patients who are blood donors should not donate blood during the study and for 3 months following their
last dose of ZS
The Estimated Number of Participants
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Taiwan
80 participants
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Global
443 participants
