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

Hyperkalemia Clinical Trial

— HARMONIZE Asia  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03528681
• Other study ID #: D9480C00001
• Status: Completed
• Phase: Phase 3
• Start date: May 6, 2021
• Est. completion date: September 15, 2022

Study information

• Verified date: October 2022
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• 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

Related Conditions & MeSH terms

• Hyperkalemia

Intervention

Drug:
• 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.
• 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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

China, 

Outcome

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