Hyperkalemia Clinical Trial
— HARMONIZE AsiaOfficial 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
Verified date | October 2022 |
Source | AstraZeneca |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
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 |
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 |
Lead Sponsor | Collaborator |
---|---|
AstraZeneca |
China,
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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