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

August 6, 2020 updated by: AstraZeneca

A Phase 3 Multicenter, Prospective, Randomized, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of ZS, in Patients With Hyperkalemia-HARMONIZE Global

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 two days of initial ZS therapy (10g TID).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
267

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Chiba-shi, Japan, 260-8712
        • Research Site
      • Hanyu-shi, Japan, 348-8505
        • Research Site
      • Hitachinaka-shi, Japan, 312-0057
        • Research Site
      • Ina-shi, Japan, 396-8555
        • Research Site
      • Kanazawa-shi, Japan, 920-8650
        • Research Site
      • Koga-shi, Japan, 306-0041
        • Research Site
      • Matsudo-shi, Japan, 271-0077
        • Research Site
      • Nagoya-shi, Japan, 457-8511
        • Research Site
      • Nagoya-shi, Japan, 462-0802
        • Research Site
      • Shimajiri-gun, Japan, 901-0493
        • Research Site
      • Shizuoka-shi, Japan, 421-0117
        • Research Site
      • Toride-shi, Japan, 302-0022
        • Research Site
      • Toyohashi-shi, Japan, 441-8570
        • Research Site
      • Yao-shi, Japan, 581-0011
        • Research Site
  • Korea, Republic of
      • Anyang-si, Korea, Republic of, 14068
        • Research Site
      • Bucheon-si, Korea, Republic of, 14754
        • Research Site
      • Bucheon-si, Korea, Republic of, 14647
        • Research Site
      • Busan, Korea, Republic of, 49241
        • Research Site
      • Cheongju-si, Korea, Republic of, 28644
        • Research Site
      • Goyang-si, Korea, Republic of, 10380
        • Research Site
      • Goyang-si, Korea, Republic of, 10444
        • Research Site
      • Gwangju, Korea, Republic of, 61469
        • Research Site
      • Hwaseong-si, Korea, Republic of, 18450
        • Research Site
      • Incheon, Korea, Republic of, 403-720
        • Research Site
      • Incheon, Korea, Republic of, 405-760
        • Research Site
      • Seoul, Korea, Republic of, 03080
        • Research Site
      • Seoul, Korea, Republic of, 06591
        • Research Site
      • Seoul, Korea, Republic of, 03312
        • Research Site
      • Seoul, Korea, Republic of, 08308
        • Research Site
      • Seoul, Korea, Republic of, 07061
        • Research Site
      • Suwon-si, Korea, Republic of
        • Research Site
      • Uijeongbu-si, Korea, Republic of, 11765
        • Research Site
      • Wonju-si, Korea, Republic of, 26426
        • Research Site
  • Russian Federation
      • Ekaterinburg, Russian Federation, 620039
        • Research Site
      • Krasnoyarsk, Russian Federation, 660062
        • Research Site
      • Moscow, Russian Federation, 123423
        • Research Site
      • Saint Petersburg, Russian Federation, 196601
        • Research Site
      • Saint-Petersburg, Russian Federation, 194354
        • Research Site
      • Yaroslavl, Russian Federation, 150062
        • Research Site
  • Taiwan
      • Hualien City, Taiwan, 970
        • Research Site
      • New Taipei, Taiwan, 231
        • Research Site
      • Taichung, Taiwan, 40705
        • Research Site
      • Taichung, Taiwan, 402
        • Research Site
      • Taipei, Taiwan
        • Research Site
      • Taipei, Taiwan, ROC 100
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Provision of informed consent prior to any study specific procedures
  • Female and male patients aged ≥18 and ≤ 90 years
  • 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 48-hour 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 and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy.

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
  • Pseudohyperkalemia signs and symptoms
  • 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
  • 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
  • Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
  • Patients with cardiac arrhythmias that require immediate treatment
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Sodium Zirconium Cyclosilicate (ZS) 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
Drug: Sodium Zirconium Cyclosilicate (ZS) 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
EXPERIMENTAL: Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
Drug: Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally three times per day, in the first 48-hour of the study for all patients (48-hour open label initial phase)
Drug: Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
PLACEBO_COMPARATOR: Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
Drug: Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Least Square Mean S-K Level on Days 8-29
Time Frame: Through 28-day randomized treatment study phase day 8-29.
Comparison between placebo and the active ZS treatment groups (each dose group will be sequentially compared with placebo, starting with the highest and ending with the lowest dose) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29. The results in the table below are presented for RTP.
Through 28-day randomized treatment study phase day 8-29.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of Patients Achieving Normokalemia
Time Frame: Through 48-hour initial phase.
Proportion of patients who achieve normokalemia during the initial phase at 24 and 48 hours. The results in the table below are presented for OLP. (h=hours).
Through 48-hour initial phase.
Exponential Rate of Change in S-K Levels
Time Frame: Through 48-hour initial phase.
Exponential rate of change in S-K levels (blood) during the 48-hour open-label initial phase. The results in the table below are presented for OLP.
Through 48-hour initial phase.
Absolute Change From Baseline in S-K Levels
Time Frame: Through 48-hour initial phase.
Absolute change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.
Through 48-hour initial phase.
Percentage Change From Baseline in S-K Levels
Time Frame: Through 48-hour initial phase.
Percentage change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.
Through 48-hour initial phase.
Proportion of Patients Remaining Normokalemic
Time Frame: Through 28-day randomized treatment study phase day 8-29.
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. The results in the table below are presented for RTP.
Through 28-day randomized treatment study phase day 8-29.
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Time Frame: Through 28-day randomized treatment phase.
The proportion of patients who are normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) at Day 1 through Day 29/Exit in randomization phase. The results in the table below are presented for RTP.
Through 28-day randomized treatment phase.
Days Patients Remain Normokalemic
Time Frame: Through 28-day randomized treatment phase.
The number of days patients remain normokalemic during the 28-day randomized treatment study phase. The results in the table below are presented for RTP.
Through 28-day randomized treatment phase.
Mean Change in S-K Levels
Time Frame: Through 28-day randomized treatment phase.
The mean change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.
Through 28-day randomized treatment phase.
Mean Percentage Change in S-K Levels
Time Frame: Through 28-day randomized treatment phase.
The mean percentage change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.
Through 28-day randomized treatment phase.
Number of Hyperkalemic Patients
Time Frame: Through 28-day randomized treatment phase.
The results represent number of hyperkalemic patients during the 28-day randomized treatment study phase. The results in the table below are presented for RTP.
Through 28-day randomized treatment phase.
Mean Changes in S-Aldosterone and P Renin Levels
Time Frame: Through 28-day randomized treatment phase.
The mean changes from OLP baseline in S-Aldosterone and P-Renin levels. The results in the table below are presented for RTP.
Through 28-day randomized treatment phase.
Patient Reported Health State (EQ-5D) Questionnaire
Time Frame: Through study completion, an average of 37 days.
Evaluate health state of patients using EQ-5D questionnaire. This scale is numbered from 0 to 100. 0 means the worst health you can imagine. 100 means the best health you can imagine. The results in the table below are presented for RTP.
Through study completion, an average of 37 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 3, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 14, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 14, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 22, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 23, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 19, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D9480C00002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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