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

Hyperkalemia Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02875834
• Other study ID #: D9480C00002
• Status: Completed
• Phase: Phase 3
• Start date: March 3, 2017
• Est. completion date: February 14, 2018

Study information

• Verified date: August 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 267
• Est. completion date: February 14, 2018
• Est. primary completion date: February 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperkalemia

Intervention

Drug:
• Sodium Zirconium Cyclosilicate (ZS) 10g
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
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
• Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
• Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.

Locations

Country	Name	City	State
Japan	Research Site	Chiba-shi
Japan	Research Site	Hanyu-shi
Japan	Research Site	Hitachinaka-shi
Japan	Research Site	Ina-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Koga-shi
Japan	Research Site	Matsudo-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Shimajiri-gun
Japan	Research Site	Shizuoka-shi
Japan	Research Site	Toride-shi
Japan	Research Site	Toyohashi-shi
Japan	Research Site	Yao-shi
Korea, Republic of	Research Site	Anyang-si
Korea, Republic of	Research Site	Bucheon-si
Korea, Republic of	Research Site	Bucheon-si
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Gwangju
Korea, Republic of	Research Site	Hwaseong-si
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon-si
Korea, Republic of	Research Site	Uijeongbu-si
Korea, Republic of	Research Site	Wonju-si
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Krasnoyarsk
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Yaroslavl
Taiwan	Research Site	Hualien City
Taiwan	Research Site	New Taipei
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Russian Federation,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Through 28-day randomized treatment study phase day 8-29.
Secondary	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).	Through 48-hour initial phase.
Secondary	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.	Through 48-hour initial phase.
Secondary	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.	Through 48-hour initial phase.
Secondary	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.	Through 48-hour initial phase.
Secondary	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.	Through 28-day randomized treatment study phase day 8-29.
Secondary	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.	Through 28-day randomized treatment phase.
Secondary	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.	Through 28-day randomized treatment phase.
Secondary	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.	Through 28-day randomized treatment phase.
Secondary	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.	Through 28-day randomized treatment phase.
Secondary	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.	Through 28-day randomized treatment phase.
Secondary	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.	Through 28-day randomized treatment phase.
Secondary	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.	Through study completion, an average of 37 days.

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