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NCT Number: NCT02875834

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

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).

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Key information

Conditions

Hyperkalemia Metabolic Diseases Nutritional and Metabolic Diseases Water-Electrolyte Imbalance

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Chiba, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sodium Zirconium Cyclosilicate (ZS) 10g

Drug

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)

Sodium Zirconium Cyclosilicate (ZS) 5g

Drug

Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.

Placebo

Drug

Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

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

Acronym: HARMONIZE GL

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Aug 23, 2016
Registry last updated
Aug 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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