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HyperkalemiaPhase 3HARMONIZE GLNCT02875834

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

A Phase 3 study testing Sodium Zirconium Cyclosilicate (ZS) 10g and Sodium Zirconium Cyclosilicate (ZS) 5g in people with Hyperkalemia, run by AstraZeneca at 45 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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 two days of initial ZS therapy (10g TID). Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Hyperkalemia
What is being tested?
Sodium Zirconium Cyclosilicate (ZS) 10g and Sodium Zirconium Cyclosilicate (ZS) 5g
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
267 participants
Where
45 sitesin 4 countries
Study dates
3 Mar 2017to 14 Feb 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

45 sites in 4 countries.

45 sites in 4 countries

South Korea19 sites

  • Research Site

    Anyang-si, 14068

  • Research Site

    Bucheon-si, 14647

  • Research Site

    Bucheon-si, 14754

  • Research Site

    Busan, 49241

  • Research Site

    Cheongju-si, 28644

  • Research Site

    Goyang-si, 10380

  • Research Site

    Goyang-si, 10444

  • Research Site

    Gwangju, 61469

  • Research Site

    Hwaseong-si, 18450

  • Research Site

    Incheon, 403-720

  • Research Site

    Incheon, 405-760

  • Research Site

    Seoul, 03080

  • Research Site

    Seoul, 03312

  • Research Site

    Seoul, 06591

  • Research Site

    Seoul, 07061

  • Research Site

    Seoul, 08308

  • Research Site

    Suwon

  • Research Site

    Uijeongbu-si, 11765

  • Research Site

    Wŏnju, 26426

Other trials in South Korea

Japan14 sites

  • Research Site

    Chiba, 260-8712

  • Research Site

    Hanyu-shi, 348-8505

  • Research Site

    Hitachi-Naka, 312-0057

  • Research Site

    Ina-shi, 396-8555

  • Research Site

    Kanazawa, 920-8650

  • Research Site

    Koga-shi, 306-0041

  • Research Site

    Matsudo-shi, 271-0077

  • Research Site

    Nagoya, 457-8511

  • Research Site

    Nagoya, 462-0802

  • Research Site

    Shimajiri-gun, 901-0493

  • Research Site

    Shizuoka, 421-0117

  • Research Site

    Toride-shi, 302-0022

  • Research Site

    Toyohashi, 441-8570

  • Research Site

    Yakushi, 581-0011

Other trials in Japan

Russia6 sites

  • Research Site

    Krasnoyarsk, 660062

  • Research Site

    Moscow, 123423

  • Research Site

    Saint Petersburg, 194354

  • Research Site

    Saint Petersburg, 196601

  • Research Site

    Yaroslavl, 150062

  • Research Site

    Yekaterinburg, 620039

Other trials in Russia

Taiwan6 sites

  • Research Site

    Hualien City, 970

  • Research Site

    New Taipei City, 231

  • Research Site

    Taichung, 402

  • Research Site

    Taichung, 40705

  • Research Site

    Taipei, ROC 100

  • Research Site

    Taipei

Other trials in Taiwan

About this study

Official 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

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).

Conditions
Hyperkalemia
Being tested
Sodium Zirconium Cyclosilicate (ZS) 10g, Sodium Zirconium Cyclosilicate (ZS) 5g, Placebo
Medical subject headings
Hyperkalemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sodium Zirconium Cyclosilicate (ZS) 10gDrug

    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) 5gDrug

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

  • Sodium Zirconium Cyclosilicate (ZS) 10gDrug

    Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.

  • PlaceboDrug

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

Study groups in NCT02875834
Study groupRoleWhat they receive
Sodium Zirconium Cyclosilicate (ZS) 5gExperimentalSuspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
Receives: Drug: Sodium Zirconium Cyclosilicate (ZS) 5g
Sodium Zirconium Cyclosilicate (ZS) 10gExperimentalSuspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
Receives: Drug: Sodium Zirconium Cyclosilicate (ZS) 10g
PlaceboPlacebo comparatorSuspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Least Square Mean S-K Level on Days 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.

    Measured: Through 28-day randomized treatment study phase day 8-29.

Secondary outcomes (12)

  1. Proportion of Patients Achieving Normokalemia

    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).

    Measured: Through 48-hour initial phase.

  2. Exponential Rate of Change in S-K Levels

    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.

    Measured: Through 48-hour initial phase.

  3. Absolute Change From Baseline in S-K Levels

    Absolute change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.

    Measured: Through 48-hour initial phase.

  4. Percentage Change From Baseline in S-K Levels

    Percentage change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.

    Measured: Through 48-hour initial phase.

  5. 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. The results in the table below are presented for RTP.

    Measured: Through 28-day randomized treatment study phase day 8-29.

  6. Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit

    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.

    Measured: Through 28-day randomized treatment phase.

  7. Days Patients Remain Normokalemic

    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.

    Measured: Through 28-day randomized treatment phase.

  8. Mean Change in S-K Levels

    The mean change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.

    Measured: Through 28-day randomized treatment phase.

  9. Mean Percentage Change in S-K Levels

    The mean percentage change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.

    Measured: Through 28-day randomized treatment phase.

  10. Number of Hyperkalemic Patients

    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.

    Measured: Through 28-day randomized treatment phase.

  11. Mean Changes in S-Aldosterone and P Renin Levels

    The mean changes from OLP baseline in S-Aldosterone and P-Renin levels. The results in the table below are presented for RTP.

    Measured: Through 28-day randomized treatment phase.

  12. Patient Reported Health State (EQ-5D) Questionnaire

    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.

    Measured: Through study completion, an average of 37 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2016 (estimated)
  2. Study start3 Mar 2017
  3. Primary completion14 Feb 2018
  4. Study completion14 Feb 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
267 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02875834
Sponsor's protocol ID
D9480C00002
Acronym
HARMONIZE GL
Status last verified
Aug 2020
First submitted
22 Jul 2016
Last updated
19 Aug 2020
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sodium Zirconium Cyclosilicate (ZS) 10g and Sodium Zirconium Cyclosilicate (ZS) 5g in people with Hyperkalemia, run by AstraZeneca at 45 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in South Korea, Japan, Russia, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Least Square Mean S-K Level on Days 8-29 (time frame: Through 28-day randomized treatment study phase day 8-29.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02875834.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2020.

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