Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : Not yet recruiting
First Posted : May 18, 2018
Last Update Posted : May 24, 2019
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 two days 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 45 centers in China and India. Before patients are randomized to the double-blind phase, they will receive open-label ZS for 48 hours during the initial phase. It is expected that approximately 555 patients will need to be enrolled, to have approximately 337 patients entered into the 48-hour open-label initial phase resulting in 320 patients being randomized in the 28-day treatment study phase. Enrolment will be stopped when 320 patients have been initiated with the 28-day randomized treatment study phase.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 337 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
Estimated Study Start Date : July 15, 2019
Estimated Primary Completion Date : May 15, 2020
Estimated Study Completion Date : May 15, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Zirconium

Arm Intervention/treatment
Experimental: Sodium Zirconium Cyclosilicate 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
Drug: Sodium Zirconium Cyclosilicate 10g
Suspension administered Sodium Zirconium Cyclosilicate 10g orally once daily for 28 days after the first 48-hour open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day.

Experimental: Sodium Zirconium Cyclosilicate 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
Drug: Sodium Zirconium Cyclosilicate 5g
Suspension administered Sodium Zirconium Cyclosilicate 5g orally once daily for 28 days after the first 48-hour open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day.

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 with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day.




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. proportion of patients achieve normokalemia [ Time Frame: Through 48- hour initial phase ]
    Proportion of patients who achieve normokalemia during the 48-hour open-label initial phase at 24 and 48 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

  3. Mean change from baseline in S-K levels [ Time Frame: Through 48-hour initial phase ]
    Mean Change (absolute and percent change) from baseline in S-K levels (blood) at all measured time intervals post dose in the 48-hour open label initial phase

  4. Time to normalization in S-K levels [ Time Frame: Through 48-hour initial phase ]
    ime to normalization in S-K levels (normalization defined as S-K levels between 3.5-5.0 mmol/L, inclusive) in the 48-hour 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. Days patients remain normokalemic [ Time Frame: Through 28-day randomized treatment study phase ]
    The number of days patients remain normokalemic during the 28-day randomized treatment study phase

  7. Mean change in SK levels [ Time Frame: Through 28-day randomized treatment study phase ]
    The mean change in SK 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

  10. Mean percent change in SK levels [ Time Frame: Through 28-day randomized treatment study phase ]
    The Mean percent change in SK levels evaluated relative to both baselines


Other Outcome Measures:
  1. Serum calcium (S-Ca) [ Time Frame: Through study completion, an average of 37 days ]
    To evaluate the effect of ZS on S-Ca in both the 48-hour open-label initial phase and the 28-day randomized treatment study phase

  2. Serum magnesium (S-Mg) [ Time Frame: Through study completion, an average of 37 days ]
    To evaluate the effect of ZS on S-Mg in both the 48-hour open-label initial phase and the 28-day randomized treatment study phase

  3. Serum sodium (S-Na) [ Time Frame: Through study completion, an average of 37 days ]
    To evaluate the effect of ZS on S-Na in both the 48-hour open-label initial phase and the 28-day randomized treatment study phase

  4. Serum Phosphate (S-PO4) [ Time Frame: Through study completion, an average of 37 days ]
    To evaluate the effect of ZS on S-PO4 in both the 48-hour open-label initial phase and the 28-day randomized treatment study phase

  5. Serum Bicarbonate (S-HCO3) [ Time Frame: Through study completion, an average of 37 days ]
    To evaluate the effect of ZS on S-HCO3 in both the 48-hour open-label initial phase and the 28-day randomized treatment study phase

  6. Blood urea nitrogen (BUN) [ Time Frame: Through study completion, an average of 37 days ]
    To evaluate the effect of ZS on BUN in both the 48-hour open-label initial phase and the 28-day randomized treatment study phase

  7. Weight in kilograms [ Time Frame: Through study completion, an average of 37 days ]
    To evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  8. Pulse rate in beats/min [ Time Frame: Through study completion, an average of 37 days ]
    A sphygmomanometer will be used to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  9. Blood pressure in mmHg [ Time Frame: Through study completion, an average of 37 days ]
    A sphygmomanometer will be used to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  10. P wave duration in msec [ Time Frame: Through study completion, an average of 37 days ]
    A standard lead of the computerized quantitative 12-lead ECG will be performed to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  11. QRS durations in msec [ Time Frame: Through study completion, an average of 37 days ]
    A standard lead of the computerized quantitative 12-lead ECG will be performed to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  12. PR intervals in msec [ Time Frame: Through study completion, an average of 37 days ]
    A standard lead of the computerized quantitative 12-lead ECG will be performed to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  13. QTc intervals in msec [ Time Frame: Through study completion, an average of 37 days ]
    A standard lead of the computerized quantitative 12-lead ECG will be performed to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  14. Heart rate in beats/min [ Time Frame: Through study completion, an average of 37 days ]
    A standard lead of the computerized quantitative 12-lead ECG will be performed to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  15. Hemoglobin [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of hemoglobin level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  16. Hematocrit [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of hematocrit level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  17. Erythrocyte count [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of erythrocyte count will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  18. Leukocyte count [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of leukocyte count will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  19. Leukocyte different count [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of leukocyte different count will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  20. Platelet count [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of platelet count will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  21. Total serum protein [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of total serum protein level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  22. Serum albumin [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of serum albumin level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  23. Serum creatinine [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of serum creatinine level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  24. Total serum bilirubin [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of total serum bilirubin level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  25. Serum alkaline phosphatase [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of serum alkaline phosphatase level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  26. Serum glucose [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of serum glucose level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  27. Serum gamma-glutamyl transferase [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of serum gamma-glutamyl transferase level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  28. Serum aspartate transaminase [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of serum aspartate transaminase level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  29. Serum alanine transaminase [ Time Frame: Through study completion, an average of 37 days ]
    Blood samples for determination of serum alanine transaminase level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  30. Urine PH [ Time Frame: Through study completion, an average of 37 days ]
    Urine samples for determination of PH level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  31. Urine specific gravity [ Time Frame: Through study completion, an average of 37 days ]
    Urine samples for determination of specific gravity level will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  32. Urine glucose [ Time Frame: Through study completion, an average of 37 days ]
    Urine samples for detection of glucose will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  33. Urine ketones [ Time Frame: Through study completion, an average of 37 days ]
    Urine samples for detection of ketones will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  34. Urine bilirubin [ Time Frame: Through study completion, an average of 37 days ]
    Urine samples for detection of bilirubin will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  35. Urine urobilinogen [ Time Frame: Through study completion, an average of 37 days ]
    Urine samples for detection of urobilinogen will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  36. Blood in urine [ Time Frame: Through study completion, an average of 37 days ]
    Urine samples for detection of blood will be performed at a central laboratory to evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  37. Number of subjects with adverse events (AEs), including serious AEs (SAEs) [ Time Frame: Through study completion, an average of 37 days ]
    To evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase

  38. Percentage of subjects with adverse events (AEs), including serious AEs (SAEs) [ Time Frame: Through study completion, an average of 37 days ]
    To evaluate the safety and tolerability profiles of ZS in both the 48-hour open label initial phase and the 28-day randomized treatment study phase



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 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 48-hour 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. Patients on dialysis
  14. Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of ZS
  15. Patients who need hospitalization after taking blood samples on day 1 of the 48-hour 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
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 58 Study Locations
Sponsors and Collaborators
AstraZeneca

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03528681     History of Changes
Other Study ID Numbers: D9480C00001
First Posted: May 18, 2018    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

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