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

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Hyperkalemia

Treatments: Drug: Sodium Zirconium Cyclosilicate (ZS) 5g; Drug: Sodium Zirconium Cyclosilicate (ZS) 10g; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02875834

D9480C00002

Details and patient eligibility

About

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).

Enrollment: 267 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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267 participants in 3 patient groups, including a placebo group

Sodium Zirconium Cyclosilicate (ZS) 5g

Experimental group

Description:

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

Treatment:

Drug: Sodium Zirconium Cyclosilicate (ZS) 5g

Sodium Zirconium Cyclosilicate (ZS) 10g

Experimental group

Description:

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

Treatment:

Drug: Sodium Zirconium Cyclosilicate (ZS) 10g

Drug: Sodium Zirconium Cyclosilicate (ZS) 10g

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo