Back to resultsA Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia (HARMONIZE GL)
Primary Purpose
Hyperkalemia
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Sodium Zirconium Cyclosilicate (ZS) 10g
Sodium Zirconium Cyclosilicate (ZS) 5g
Sodium Zirconium Cyclosilicate (ZS) 10g
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hyperkalemia
Eligibility Criteria
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Sodium Zirconium Cyclosilicate (ZS) 5g
Sodium Zirconium Cyclosilicate (ZS) 10g
Placebo
Arm Description
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02875834
Brief Title
A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia
Acronym
HARMONIZE GL
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
March 3, 2017 (Actual)
Primary Completion Date
February 14, 2018 (Actual)
Study Completion Date
February 14, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperkalemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
267 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sodium Zirconium Cyclosilicate (ZS) 5g
Arm Type
Experimental
Arm Description
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
Arm Title
Sodium Zirconium Cyclosilicate (ZS) 10g
Arm Type
Experimental
Arm Description
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
Intervention Type
Drug
Intervention Name(s)
Sodium Zirconium Cyclosilicate (ZS) 10g
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Sodium Zirconium Cyclosilicate (ZS) 5g
Intervention Description
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
Intervention Type
Drug
Intervention Name(s)
Sodium Zirconium Cyclosilicate (ZS) 10g
Intervention Description
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
Primary Outcome Measure Information:
Title
Least Square Mean S-K Level on Days 8-29
Description
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.
Time Frame
Through 28-day randomized treatment study phase day 8-29.
Secondary Outcome Measure Information:
Title
Proportion of Patients Achieving Normokalemia
Description
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).
Time Frame
Through 48-hour initial phase.
Title
Exponential Rate of Change in S-K Levels
Description
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.
Time Frame
Through 48-hour initial phase.
Title
Absolute Change From Baseline in S-K Levels
Description
Absolute change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.
Time Frame
Through 48-hour initial phase.
Title
Percentage Change From Baseline in S-K Levels
Description
Percentage change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.
Time Frame
Through 48-hour initial phase.
Title
Proportion of Patients Remaining Normokalemic
Description
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.
Time Frame
Through 28-day randomized treatment study phase day 8-29.
Title
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Description
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.
Time Frame
Through 28-day randomized treatment phase.
Title
Days Patients Remain Normokalemic
Description
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.
Time Frame
Through 28-day randomized treatment phase.
Title
Mean Change in S-K Levels
Description
The mean change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.
Time Frame
Through 28-day randomized treatment phase.
Title
Mean Percentage Change in S-K Levels
Description
The mean percentage change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.
Time Frame
Through 28-day randomized treatment phase.
Title
Number of Hyperkalemic Patients
Description
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.
Time Frame
Through 28-day randomized treatment phase.
Title
Mean Changes in S-Aldosterone and P Renin Levels
Description
The mean changes from OLP baseline in S-Aldosterone and P-Renin levels. The results in the table below are presented for RTP.
Time Frame
Through 28-day randomized treatment phase.
Title
Patient Reported Health State (EQ-5D) Questionnaire
Description
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.
Time Frame
Through study completion, an average of 37 days.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Research Site
City
Chiba-shi
ZIP/Postal Code
260-8712
Country
Japan
Facility Name
Research Site
City
Hanyu-shi
ZIP/Postal Code
348-8505
Country
Japan
Facility Name
Research Site
City
Hitachinaka-shi
ZIP/Postal Code
312-0057
Country
Japan
Facility Name
Research Site
City
Ina-shi
ZIP/Postal Code
396-8555
Country
Japan
Facility Name
Research Site
City
Kanazawa-shi
ZIP/Postal Code
920-8650
Country
Japan
Facility Name
Research Site
City
Koga-shi
ZIP/Postal Code
306-0041
Country
Japan
Facility Name
Research Site
City
Matsudo-shi
ZIP/Postal Code
271-0077
Country
Japan
Facility Name
Research Site
City
Nagoya-shi
ZIP/Postal Code
457-8511
Country
Japan
Facility Name
Research Site
City
Nagoya-shi
ZIP/Postal Code
462-0802
Country
Japan
Facility Name
Research Site
City
Shimajiri-gun
ZIP/Postal Code
901-0493
Country
Japan
Facility Name
Research Site
City
Shizuoka-shi
ZIP/Postal Code
421-0117
Country
Japan
Facility Name
Research Site
City
Toride-shi
ZIP/Postal Code
302-0022
Country
Japan
Facility Name
Research Site
City
Toyohashi-shi
ZIP/Postal Code
441-8570
Country
Japan
Facility Name
Research Site
City
Yao-shi
ZIP/Postal Code
581-0011
Country
Japan
Facility Name
Research Site
City
Anyang-si
ZIP/Postal Code
14068
Country
Korea, Republic of
Facility Name
Research Site
City
Bucheon-si
ZIP/Postal Code
14647
Country
Korea, Republic of
Facility Name
Research Site
City
Bucheon-si
ZIP/Postal Code
14754
Country
Korea, Republic of
Facility Name
Research Site
City
Busan
ZIP/Postal Code
49241
Country
Korea, Republic of
Facility Name
Research Site
City
Cheongju-si
ZIP/Postal Code
28644
Country
Korea, Republic of
Facility Name
Research Site
City
Goyang-si
ZIP/Postal Code
10380
Country
Korea, Republic of
Facility Name
Research Site
City
Goyang-si
ZIP/Postal Code
10444
Country
Korea, Republic of
Facility Name
Research Site
City
Gwangju
ZIP/Postal Code
61469
Country
Korea, Republic of
Facility Name
Research Site
City
Hwaseong-si
ZIP/Postal Code
18450
Country
Korea, Republic of
Facility Name
Research Site
City
Incheon
ZIP/Postal Code
403-720
Country
Korea, Republic of
Facility Name
Research Site
City
Incheon
ZIP/Postal Code
405-760
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03312
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
07061
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
08308
Country
Korea, Republic of
Facility Name
Research Site
City
Suwon-si
Country
Korea, Republic of
Facility Name
Research Site
City
Uijeongbu-si
ZIP/Postal Code
11765
Country
Korea, Republic of
Facility Name
Research Site
City
Wonju-si
ZIP/Postal Code
26426
Country
Korea, Republic of
Facility Name
Research Site
City
Ekaterinburg
ZIP/Postal Code
620039
Country
Russian Federation
Facility Name
Research Site
City
Krasnoyarsk
ZIP/Postal Code
660062
Country
Russian Federation
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
123423
Country
Russian Federation
Facility Name
Research Site
City
Saint Petersburg
ZIP/Postal Code
196601
Country
Russian Federation
Facility Name
Research Site
City
Saint-Petersburg
ZIP/Postal Code
194354
Country
Russian Federation
Facility Name
Research Site
City
Yaroslavl
ZIP/Postal Code
150062
Country
Russian Federation
Facility Name
Research Site
City
Hualien City
ZIP/Postal Code
970
Country
Taiwan
Facility Name
Research Site
City
New Taipei
ZIP/Postal Code
231
Country
Taiwan
Facility Name
Research Site
City
Taichung
ZIP/Postal Code
402
Country
Taiwan
Facility Name
Research Site
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
Research Site
City
Taipei
ZIP/Postal Code
ROC 100
Country
Taiwan
Facility Name
Research Site
City
Taipei
Country
Taiwan
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=4401&filename=d9480c00002-sap-ed-2_Redacted_CTT.PDF
Description
Related Info
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=4401&filename=d9480c00002-csp-v3_Redacted_CTT.PDF
Description
Related Info
Learn more about this trial
A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia
We'll reach out to this number within 24 hrs