Trial Outcomes & Findings for A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia. (NCT NCT03528681)

Last Updated: 2025-05-14

Results Overview

Comparison between placebo and each SZC treatment group (high to low) with regard to the mean S-K level during the randomized treatment phase days 8-29. Mixed-effects models were used to estimate least-squares means.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

270 participants

Primary outcome timeframe

Days 8 to 29 (Randomized treatment study phase) used for model-based least squares mean computation

Results posted on

2025-05-14

Participant Flow

The study was conducted in 35 sites in China.

The study consisted of two phases, an Open-label initial phase (OLP) and a Randomized treatment phase (RTP). 270 participants entered OLP, out of these 250 entered RTP \& received Placebo, SZC 5g QD, or SZC 10g QD in a 1:2:2 ratio.

Participant milestones

Participant milestones
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Open-Label Phase STARTED	270	0	0	0
Open-Label Phase COMPLETED	256	0	0	0
Open-Label Phase NOT COMPLETED	14	0	0	0
Randomized Treatment Phase STARTED	0	100	100	50
Randomized Treatment Phase COMPLETED	0	81	85	38
Randomized Treatment Phase NOT COMPLETED	0	19	15	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Open-Label Phase Physician Decision	2	0	0	0
Open-Label Phase Withdrawal by Subject	8	0	0	0
Open-Label Phase (Not collected)	4	0	0	0
Randomized Treatment Phase Lost to Follow-up	0	0	1	0
Randomized Treatment Phase Physician Decision	0	5	1	2
Randomized Treatment Phase Withdrawal by Subject	0	7	4	1
Randomized Treatment Phase (Study specific withdrawal criteria)	0	3	3	4
Randomized Treatment Phase (Not collected)	0	4	6	5

Baseline Characteristics

Two phases reported as separate rows to avoid double counting

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sodium Zirconium Cyclosilicate (SZC) n=270 Participants Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=100 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=100 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=50 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.	Total n=520 Participants Total of all reporting groups
Age, Continuous Randomized treatment phase (RTP)	—	54.3 Years STANDARD_DEVIATION 13.92 • n=100 Participants • Two phases reported as separate rows to avoid double counting	55.6 Years STANDARD_DEVIATION 14.47 • n=100 Participants • Two phases reported as separate rows to avoid double counting	59.7 Years STANDARD_DEVIATION 14.2 • n=50 Participants • Two phases reported as separate rows to avoid double counting	55.9 Years STANDARD_DEVIATION 14.28 • n=250 Participants • Two phases reported as separate rows to avoid double counting
Age, Continuous Open-label initial phase (OLP)	56.4 Years STANDARD_DEVIATION 14.17 • n=270 Participants • Two phases reported as separate rows to avoid double counting	—	—	—	56.4 Years STANDARD_DEVIATION 14.17 • n=270 Participants • Two phases reported as separate rows to avoid double counting
Sex: Female, Male Randomized treatment phase (RTP) · Female	—	35 Participants n=100 Participants • Two phases reported as separate rows to avoid double counting	40 Participants n=100 Participants • Two phases reported as separate rows to avoid double counting	19 Participants n=50 Participants • Two phases reported as separate rows to avoid double counting	94 Participants n=250 Participants • Two phases reported as separate rows to avoid double counting
Sex: Female, Male Randomized treatment phase (RTP) · Male	—	65 Participants n=100 Participants • Two phases reported as separate rows to avoid double counting	60 Participants n=100 Participants • Two phases reported as separate rows to avoid double counting	31 Participants n=50 Participants • Two phases reported as separate rows to avoid double counting	156 Participants n=250 Participants • Two phases reported as separate rows to avoid double counting
Sex: Female, Male Open-label initial phase (OLP) · Female	103 Participants n=270 Participants • Two phases reported as separate rows to avoid double counting	—	—	—	103 Participants n=270 Participants • Two phases reported as separate rows to avoid double counting
Sex: Female, Male Open-label initial phase (OLP) · Male	167 Participants n=270 Participants • Two phases reported as separate rows to avoid double counting	—	—	—	167 Participants n=270 Participants • Two phases reported as separate rows to avoid double counting
Race/Ethnicity, Customized Not Hispanic or Latino Randomized treatment phase (RTP)	—	100 Participants n=100 Participants • Two phases reported as separate rows to avoid double counting	100 Participants n=100 Participants • Two phases reported as separate rows to avoid double counting	50 Participants n=50 Participants • Two phases reported as separate rows to avoid double counting	250 Participants n=250 Participants • Two phases reported as separate rows to avoid double counting
Race/Ethnicity, Customized Not Hispanic or Latino Open-label initial phase (OLP)	270 Participants n=270 Participants • Two phases reported as separate rows to avoid double counting	—	—	—	270 Participants n=270 Participants • Two phases reported as separate rows to avoid double counting

PRIMARY outcome

Timeframe: Days 8 to 29 (Randomized treatment study phase) used for model-based least squares mean computation

Population: Full analysis set - Randomized Treatment Phase

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=99 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=99 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=50 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Least Square Mean S-K Level on Days 8-29	—	4.859 mmol/L Interval 4.709 to 5.014	4.440 mmol/L Interval 4.304 to 4.58	5.225 mmol/L Interval 5.055 to 5.4

SECONDARY outcome

Timeframe: Through open label initial phase

Population: Full analysis set - Open Label Phase

Percentage of patients who achieve normokalemia during the open label initial phase at 24 hours and at the end of the open label phase. End of OLP is defined as Day 2 (24 hours post first dose) or Day 3 (48 hours post first dose) depending on when the subject achieved normokalemia based on the pre-dose i-STAT potassium level. The results in the table below are presented for OLP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID n=261 Participants Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Percentage of Patients Who Achieve Normokalemia Normokalemic at 24h	180 Participants	—	—	—
Percentage of Patients Who Achieve Normokalemia Normokalemic at End of OLP	228 Participants	—	—	—

SECONDARY outcome

Timeframe: Through 24 hours post-dose in the initial phase

Population: Full analysis set - Open Label Phase

Exponential rate of change in S-K levels (blood) during the open-label initial phase 24 hours post-dose. Least Square Mean corresponds to the exponential rate of change i.e. the slope (for time) in terms of log-transformed S-K levels. The results in the table below are presented for OLP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID n=270 Participants Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Exponential Rate of Change in S-K Levels	-0.0051 log(mmol/L)/h Standard Error 0.00027	—	—	—

SECONDARY outcome

Timeframe: Through open label initial phase

Population: Full analysis set - Open Label Phase

Absolute change from baseline in S-K levels at all measured time intervals. End of OLP is defined as Day 2 (24 hours post first dose) or Day 3 (48 hours post first dose) depending on when the subject achieved normokalemia based on the pre-dose i-STAT potassium level. The results in the table below are presented for OLP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID n=261 Participants Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Absolute Change From Baseline in S-K Levels OLP - 24 hours	-0.936 mmol/L Standard Deviation 0.377	—	—	—
Absolute Change From Baseline in S-K Levels End of OLP	-1.107 mmol/L Standard Deviation 0.466	—	—	—

SECONDARY outcome

Timeframe: Through open label initial phase

Population: Full analysis set - Open Label Phase

Percentage change from baseline in S-K levels at all measured time intervals. End of OLP is defined as Day 2 (24 hours post first dose) or Day 3 (48 hours post first dose) depending on when the subject achieved normokalemia based on the pre-dose i-STAT potassium level. The results in the table below are presented for OLP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID n=261 Participants Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Percentage Change From Baseline in S-K Levels OLP - 24 hours	-15.880 Percentage Standard Deviation 5.980	—	—	—
Percentage Change From Baseline in S-K Levels End of OLP	-18.588 Percentage Standard Deviation 6.701	—	—	—

SECONDARY outcome

Timeframe: Through 28-day randomized treatment study phase day 8-29

Population: Full analysis set - Randomized Treatment Phase

Proportion of patients who remain normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) during RTP (Day 8 to Day 29). The results in the table below are presented for RTP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=99 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=98 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=50 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Proportion of Patients Who Remain Normokalemic During RTP	—	0.596 Average probability	0.818 Average probability	0.279 Average probability

SECONDARY outcome

Timeframe: The end of 28-day randomized treatment study phase

Population: Full analysis set - Randomized Treatment Phase

Proportion of normokalemic patients (as defined by S-K between 3.5-5.0 mmol/l, inclusive). The results in the table below are presented for RTP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=80 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=85 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=38 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Proportion of Normokalemic Patients at the End of RTP	—	47 Participants	65 Participants	14 Participants

SECONDARY outcome

Timeframe: Through days 8-29 of the randomized treatment phase.

Population: Full analysis set - Randomized Treatment Phase

The number of days patients remain normokalemic during days 8-29 of the randomized treatment study phase. The results in the table below are presented for RTP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=99 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=98 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=50 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Days Patients Remain Normokalemic	—	9.11 Day Standard Error 1.413	14.54 Day Standard Error 1.397	3.40 Day Standard Error 1.473

SECONDARY outcome

Timeframe: Through 28-day randomized treatment phase.

Population: Full analysis set - Randomized Treatment Phase

The mean change in S-K levels evaluated relative to the RTP baseline. The results in the table below are presented for RTP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=98 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=99 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=50 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Mean Change in S-K Levels Day 29 change from RTP baseline	—	0.23 mmol/L Standard Deviation 0.494	0.01 mmol/L Standard Deviation 0.578	0.47 mmol/L Standard Deviation 0.520
Mean Change in S-K Levels Day 2 change from RTP baseline	—	-0.04 mmol/L Standard Deviation 0.299	-0.15 mmol/L Standard Deviation 0.314	0.02 mmol/L Standard Deviation 0.315
Mean Change in S-K Levels Day 5 change from RTP baseline	—	0.09 mmol/L Standard Deviation 0.434	-0.27 mmol/L Standard Deviation 0.464	0.40 mmol/L Standard Deviation 0.423
Mean Change in S-K Levels Day 8 change from RTP baseline	—	0.20 mmol/L Standard Deviation 0.481	-0.29 mmol/L Standard Deviation 0.541	0.53 mmol/L Standard Deviation 0.485
Mean Change in S-K Levels Day 12 change from RTP baseline	—	0.25 mmol/L Standard Deviation 0.539	-0.23 mmol/L Standard Deviation 0.597	0.67 mmol/L Standard Deviation 0.452
Mean Change in S-K Levels Day 15 change from RTP baseline	—	0.26 mmol/L Standard Deviation 0.557	-0.24 mmol/L Standard Deviation 0.581	0.67 mmol/L Standard Deviation 0.494
Mean Change in S-K Levels Day 19 change from RTP baseline	—	0.41 mmol/L Standard Deviation 0.606	-0.19 mmol/L Standard Deviation 0.616	0.61 mmol/L Standard Deviation 0.506
Mean Change in S-K Levels Day 22 change from RTP baseline	—	0.32 mmol/L Standard Deviation 0.543	-0.13 mmol/L Standard Deviation 0.538	0.62 mmol/L Standard Deviation 0.536
Mean Change in S-K Levels Day 26 change from RTP baseline	—	0.22 mmol/L Standard Deviation 0.556	-0.05 mmol/L Standard Deviation 0.627	0.55 mmol/L Standard Deviation 0.447
Mean Change in S-K Levels EOS change from RTP baseline	—	0.57 mmol/L Standard Deviation 0.499	0.67 mmol/L Standard Deviation 0.688	0.55 mmol/L Standard Deviation 0.667

SECONDARY outcome

Timeframe: Through 28-day randomized treatment phase.

Population: Full analysis set - Randomized Treatment Phase

The mean percent change in S-K levels evaluated relative to the RTP baseline. The results in the table below are presented for RTP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=98 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=99 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=50 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Mean Percent Change in S-K Levels Day 2 change from RTP baseline	—	-0.81 Percent change Standard Deviation 6.308	-3.13 Percent change Standard Deviation 6.627	0.41 Percent change Standard Deviation 6.670
Mean Percent Change in S-K Levels Day 5 change from RTP baseline	—	2.10 Percent change Standard Deviation 9.009	-5.57 Percent change Standard Deviation 9.688	8.56 Percent change Standard Deviation 8.989
Mean Percent Change in S-K Levels Day 8 change from RTP baseline	—	4.45 Percent change Standard Deviation 10.260	-6.05 Percent change Standard Deviation 11.352	11.24 Percent change Standard Deviation 9.989
Mean Percent Change in S-K Levels Day 12 change from RTP baseline	—	5.55 Percent change Standard Deviation 11.564	-4.65 Percent change Standard Deviation 12.604	14.39 Percent change Standard Deviation 9.908
Mean Percent Change in S-K Levels Day 15 change from RTP baseline	—	5.85 Percent change Standard Deviation 11.840	-4.85 Percent change Standard Deviation 12.107	14.50 Percent change Standard Deviation 10.775
Mean Percent Change in S-K Levels Day 19 change from RTP baseline	—	9.01 Percent change Standard Deviation 13.285	-3.76 Percent change Standard Deviation 12.797	13.34 Percent change Standard Deviation 11.266
Mean Percent Change in S-K Levels Day 22 change from RTP baseline	—	7.09 Percent change Standard Deviation 11.952	-2.59 Percent change Standard Deviation 11.292	13.15 Percent change Standard Deviation 11.686
Mean Percent Change in S-K Levels Day 26 change from RTP baseline	—	5.12 Percent change Standard Deviation 12.130	-0.76 Percent change Standard Deviation 13.278	11.95 Percent change Standard Deviation 9.809
Mean Percent Change in S-K Levels Day 29 change from RTP baseline	—	5.24 Percent change Standard Deviation 10.941	0.48 Percent change Standard Deviation 12.142	10.20 Percent change Standard Deviation 11.438
Mean Percent Change in S-K Levels EOS change from RTP baseline	—	12.42 Percent change Standard Deviation 11.054	14.47 Percent change Standard Deviation 14.797	11.74 Percent change Standard Deviation 14.477

SECONDARY outcome

Timeframe: Through 28 day randomized treatment study phase day 15-29

Population: Full analysis set - Randomized Treatment Phase

Comparison between placebo and each SZC treatment group (high to low) with regard to the mean S-Aldo and P-Renin levels during the randomized treatment phase days 15-29.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=88 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=92 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=46 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Least Square Mean Changes in S-Aldo and P-Renin Levels S-Aldo	—	-21.926 pmol/L Interval -80.492 to 36.64	-53.945 pmol/L Interval -112.189 to 4.3	83.322 pmol/L Interval 22.519 to 144.124
Least Square Mean Changes in S-Aldo and P-Renin Levels P-Renin	—	-0.348 pmol/L Interval -0.484 to -0.212	-0.424 pmol/L Interval -0.559 to -0.288	-0.362 pmol/L Interval -0.505 to -0.218

SECONDARY outcome

Timeframe: Day 29

Population: Full analysis set - Randomized Treatment Phase

The number of patients with hyperkalaemia at day 29. The results in the table below are presented for RTP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=100 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=99 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=50 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Hyperkalaemia at Day 29	—	77 Participants	50 Participants	48 Participants

SECONDARY outcome

Timeframe: Day 29 of randomized treatment phase

Population: Full analysis set - Randomized Treatment Phase

Kaplan-Meier estimate at Day 29 of percentage of patients without hyperkalemia. The results in the table below are presented for RTP.

Outcome measures

Outcome measures
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=100 Participants Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=99 Participants Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=50 Participants Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Percentage of Patients Without Hyperkalemia	—	20.3 Percentage Interval 12.8 to 29.0	47.1 Percentage Interval 36.5 to 57.0	4.0 Percentage Interval 0.7 to 12.1

Adverse Events

Sodium Zirconium Cyclosilicate (SZC) 10g TID

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Sodium Zirconium Cyclosilicate (SZC) 5g QD

Serious events: 6 serious events

Other events: 48 other events

Deaths: 0 deaths

Sodium Zirconium Cyclosilicate (SZC) 10g QD

Serious events: 3 serious events

Other events: 42 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sodium Zirconium Cyclosilicate (SZC) 10g TID n=270 participants at risk Suspension administered 10g orally 3 times per day for the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 5g QD n=100 participants at risk Suspension administered 5g orally once daily for 28 days after the open-label initial phase	Sodium Zirconium Cyclosilicate (SZC) 10g QD n=100 participants at risk Suspension administered 10g orally once daily for 28 days after the open-label initial phase	Placebo n=50 participants at risk Suspension administered placebo orally once daily for 28 days after the open-label initial phase.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/270 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/100 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/100 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	2.0% 1/50 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/270 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	1.0% 1/100 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/100 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/50 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.
General disorders Oedema	0.00% 0/270 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/100 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	1.0% 1/100 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/50 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.
General disorders Oedema peripheral	0.00% 0/270 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	1.0% 1/100 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/100 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/50 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.
Metabolism and nutrition disorders Hyperkalaemia	0.37% 1/270 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	1.0% 1/100 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	1.0% 1/100 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/50 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.
Renal and urinary disorders Chronic kidney disease	0.00% 0/270 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	1.0% 1/100 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/100 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/50 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.
Renal and urinary disorders End stage renal disease	0.00% 0/270 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	1.0% 1/100 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	1.0% 1/100 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/50 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/270 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	1.0% 1/100 • Number of events 1 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/100 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.	0.00% 0/50 • Adverse Events were collected from the time of the main study informed consent (Day 1, Visit 3) throughout the treatment period and including the End of Study (EOS) visit. Serious Adverse Events were collected from the time of the optional Pre-screening informed consent (Visit 1) throughout the treatment period and including the EOS visit. Maximum duration of treatment was 8 days for open-label initial phase and 30 days for the randomized treatment phase.

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place