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

Phase 3

Completed

Conditions: Hyperkalemia

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

Registration Number: NCT02875834

Lead Sponsor: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 267

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Least Square Mean S-K Level on Days 8-29	Through 28-day randomized treatment study phase day 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

Name	Time	Method
Proportion of Patients Achieving Normokalemia	Through 48-hour initial phase.	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	Through 48-hour initial phase.	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	Through 48-hour initial phase.	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	Through 48-hour initial phase.	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	Through 28-day randomized treatment study phase day 8-29.	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	Through 28-day randomized treatment phase.	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	Through 28-day randomized treatment phase.	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	Through 28-day randomized treatment phase.	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	Through 28-day randomized treatment phase.	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	Through 28-day randomized treatment phase.	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	Through 28-day randomized treatment phase.	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	Through study completion, an average of 37 days.	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.