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A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia. (HARMONIZE Asia)

Primary Purpose

Hyperkalemia

Status

Completed

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

Sodium Zirconium Cyclosilicate 5g

Sodium Zirconium Cyclosilicate 10g

Placebo

About this trial

This is an interventional treatment trial for Hyperkalemia

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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
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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Sodium Zirconium Cyclosilicate 10g

Sodium Zirconium Cyclosilicate 5g

Matching Placebo

Arm Description

Suspension administered 10g orally once daily for 28 days after the open label initial phase.

Suspension administered 5g orally once daily for 28 days after the open label initial phase.

Suspension administered orally placebo once daily for 28 days after the open label initial phase.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Exponential rate of change in S-K levels

Exponential rate of change in S-K levels (blood) during the open label initial phase

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

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

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

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

Mean number of Days patients remain normokalemic

The mean number of days patients remain normokalemic during the 28-day randomized treatment study phase

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

Time to hyperkalemia

The time to hyperkalemia (defined as S-K ≥5.1mmol/L)

Mean changes in S-Aldo and P-Renin levels

The mean changes in S-Aldo and P-Renin levels

Full Information

NCT ID

NCT03528681

First Posted

April 16, 2018

Last Updated

October 11, 2022

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT03528681

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

May 6, 2021 (Actual)

Primary Completion Date

September 15, 2022 (Actual)

Study Completion Date

September 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperkalemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

250 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sodium Zirconium Cyclosilicate 10g

Arm Type

Experimental

Arm Description

Suspension administered 10g orally once daily for 28 days after the open label initial phase.

Arm Title

Sodium Zirconium Cyclosilicate 5g

Arm Type

Experimental

Arm Description

Suspension administered 5g orally once daily for 28 days after the open label initial phase.

Arm Title

Matching Placebo

Arm Type

Placebo Comparator

Arm Description

Suspension administered orally placebo once daily for 28 days after the open label initial phase.

Intervention Type

Drug

Intervention Name(s)

Sodium Zirconium Cyclosilicate 5g

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Sodium Zirconium Cyclosilicate 10g

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Least Squares Means of S-K values during the 28-day randomized treatment study phase Study Days 8-29.

Description

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

Time Frame

Through 28 day randomized treatment study phase day 8-29

Secondary Outcome Measure Information:

Title

Exponential rate of change in S-K levels

Description

Exponential rate of change in S-K levels (blood) during the open label initial phase

Time Frame

Through open label initial phase

Title

Mean change from baseline in S-K levels

Description

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

Time Frame

Through open label initial phase

Title

proportion of patients achieve normokalemia

Description

Proportion of patients who achieve normokalemia during the open label initial phase at 24 hours and at the end of the open label phase

Time Frame

Through open label initial phase

Title

Time to normalization in S-K levels

Description

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

Time Frame

Through open label initial phase

Title

Proportion of patients remaining normokalemic

Description

Time Frame