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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03528681
Recruitment Status : Recruiting
First Posted : May 18, 2018
Last Update Posted : May 20, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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).

Condition or disease Intervention/treatment Phase
Hyperkalemia Drug: Sodium Zirconium Cyclosilicate 5g Drug: Sodium Zirconium Cyclosilicate 10g Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : May 6, 2021
Estimated Primary Completion Date : July 14, 2022
Estimated Study Completion Date : July 14, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sodium Zirconium Cyclosilicate 10g
Suspension administered 10g orally once daily for 28 days after the open label initial phase.
Drug: 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.

Experimental: Sodium Zirconium Cyclosilicate 5g
Suspension administered 5g orally once daily for 28 days after the open label initial phase.
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.

Placebo Comparator: Matching Placebo
Suspension administered orally placebo once daily for 28 days after the open label initial phase.
Drug: 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.




Primary Outcome Measures :
  1. Least Squares Means of S-K values during the 28-day randomized treatment study phase Study Days 8-29. [ Time Frame: Through 28 day randomized treatment study phase day 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 :
  1. Exponential rate of change in S-K levels [ Time Frame: Through open label initial phase ]
    Exponential rate of change in S-K levels (blood) during the open label initial phase

  2. Mean change from baseline in S-K levels [ Time Frame: Through open label initial phase ]
    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

  3. proportion of patients achieve normokalemia [ Time Frame: Through open label initial phase ]
    Proportion of patients who achieve normokalemia during the open label initial phase at 24 hours and at the end of the open label phase

  4. Time to normalization in S-K levels [ Time Frame: Through open label initial phase ]
    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

  5. Proportion of patients remaining normokalemic [ Time Frame: Through 28-day randomized treatment study phase ]
    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

  6. Mean number of Days patients remain normokalemic [ Time Frame: Through 28-day randomized treatment study phase ]
    The mean number of days patients remain normokalemic during the 28-day randomized treatment study phase

  7. Mean change and mean percent change in S-K levels [ Time Frame: Through 28-day randomized treatment study phase ]
    The mean change and mean percent change in S-K levels evaluated relative to both baselines

  8. Time to hyperkalemia [ Time Frame: Through 28-day randomized treatment study phase ]
    The time to hyperkalemia (defined as S-K ≥5.1mmol/L)

  9. Mean changes in S-Aldo and P-Renin levels [ Time Frame: Through 28-day randomized treatment study phase ]
    The mean changes in S-Aldo and P-Renin levels


Other Outcome Measures:
  1. Vital signs [ Time Frame: Throughout the study, from the time of signature of the main study informed consent form up to study completion. ]
    Vital signs include pulse rate and blood pressure

  2. ECG measurements [ Time Frame: Throughout the study, from the time of signature of the main study informed consent form up to study completion. ]
    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.

  3. AEs, including SAEs [ Time Frame: Throughout the study, from the time of signature of the main study informed consent form up to study completion. ]
    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

  4. Safety laboratory evaluations, including determination of hypokalaemia [ Time Frame: Throughout the study, from the time of signature of the main study informed consent form up to study completion. ]
    Include, but are not limited to, serum potassium, calcium, magnesium, sodium, phosphate, bicarbonate, as well as blood urea nitrogen.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03528681


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03528681    
Other Study ID Numbers: D9480C00001
First Posted: May 18, 2018    Key Record Dates
Last Update Posted: May 20, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hyperkalemia
Water-Electrolyte Imbalance
Metabolic Diseases