Trial Outcomes & Findings for Safety & Efficacy of Zirconium Silicate in Mild to Moderate Hyperkalemia (NCT NCT01737697)

NCT ID: NCT01737697

Last Updated: 2018-10-12

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

754 participants

Primary outcome timeframe

Through 48 hours acute phase

Results posted on

2018-10-12

Participant Flow

Participants took part in the study at 65 sites (up to 100 sites initially planned in Protocol) in the United States, Australia, and South Africa from 25 November 2012 to 29 October 2013.

In the acute phase, 754 subjects were randomized; 753 were treated. Subjects who completed the AP and had i-STAT K+ values within normal range in a.m. of Study Day 3 could enter the Subacute Phase. 543 subjects entered the subacute phase.

Participant milestones

Participant milestones
Measure	Acute Phase: Placebo Participants administered placebo as suspension orally three times a day (TID) for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 TID Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: Placebo Matched to ZS 1.25g QD Participants who received ZS 1.25 g TID in the acute phase and administered placebo as suspension once daily (QD) for 12 days.	Subacute Phase: ZS 1.25 g QD Participants who received ZS 1.25g TID in the acute phase and administered ZS 1.25 g QD for 12 days.	Subacute Phase: Placebo Matched to ZS 2.5 g QD Participants who received ZS 2.5 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g QD Participants who received ZS 2.5 g TID in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 5 g QD Participants who received ZS 5 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 5 g QD Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g (Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Acute Phase-Initial 48 Hours STARTED	158	154	141	158	143	0	0	0	0	0	0	0	0	0	0
Acute Phase-Initial 48 Hours COMPLETED	157	150	137	152	140	0	0	0	0	0	0	0	0	0	0
Acute Phase-Initial 48 Hours NOT COMPLETED	1	4	4	6	3	0	0	0	0	0	0	0	0	0	0
Subacute Phase STARTED	0	0	0	0	0	41	49	46	54	68	65	61	63	46	50
Subacute Phase COMPLETED	0	0	0	0	0	38	48	43	52	66	59	58	61	44	49
Subacute Phase NOT COMPLETED	0	0	0	0	0	3	1	3	2	2	6	3	2	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Acute Phase: Placebo Participants administered placebo as suspension orally three times a day (TID) for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 TID Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: Placebo Matched to ZS 1.25g QD Participants who received ZS 1.25 g TID in the acute phase and administered placebo as suspension once daily (QD) for 12 days.	Subacute Phase: ZS 1.25 g QD Participants who received ZS 1.25g TID in the acute phase and administered ZS 1.25 g QD for 12 days.	Subacute Phase: Placebo Matched to ZS 2.5 g QD Participants who received ZS 2.5 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g QD Participants who received ZS 2.5 g TID in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 5 g QD Participants who received ZS 5 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 5 g QD Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g (Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Acute Phase-Initial 48 Hours Adverse Event	0	1	0	1	1	0	0	0	0	0	0	0	0	0	0
Acute Phase-Initial 48 Hours hypo-or hyperkalemia	1	1	3	0	0	0	0	0	0	0	0	0	0	0	0
Acute Phase-Initial 48 Hours Family emergency	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Acute Phase-Initial 48 Hours Sponsor's decision	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Acute Phase-Initial 48 Hours Lost to Follow-up	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Acute Phase-Initial 48 Hours Withdrawal by Subject	0	1	1	4	1	0	0	0	0	0	0	0	0	0	0
Subacute Phase Adverse Event	0	0	0	0	0	1	1	1	1	1	4	1	1	0	0
Subacute Phase Withdrawal by Subject	0	0	0	0	0	1	0	2	0	1	0	1	1	1	0
Subacute Phase Lost to Follow-up	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Subacute Phase Hypo-or hyperkalemia	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Subacute Phase Protocol Violation	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0
Subacute Phase Physician Decision	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Subacute Phase Death	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0

Baseline Characteristics

Subjects with non-missing acute phase baseline eGFR

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Acute Phase: Placebo TID n=158 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=154 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=141 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=157 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 TID n=143 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Total n=753 Participants Total of all reporting groups
Age, Customized Acute Phase	65.6 Years STANDARD_DEVIATION 12.24 • n=158 Participants	65.4 Years STANDARD_DEVIATION 13.07 • n=154 Participants	65.9 Years STANDARD_DEVIATION 11.73 • n=141 Participants	65.2 Years STANDARD_DEVIATION 11.91 • n=157 Participants	66.2 Years STANDARD_DEVIATION 12.16 • n=143 Participants	65.6 Years STANDARD_DEVIATION 12.24 • n=753 Participants
Sex/Gender, Customized Female	60 Participants n=158 Participants	71 Participants n=154 Participants	50 Participants n=141 Participants	61 Participants n=157 Participants	63 Participants n=143 Participants	305 Participants n=753 Participants
Sex/Gender, Customized Male	98 Participants n=158 Participants	83 Participants n=154 Participants	91 Participants n=141 Participants	96 Participants n=157 Participants	80 Participants n=143 Participants	448 Participants n=753 Participants
Race/Ethnicity, Customized White	136 Participants n=158 Participants	131 Participants n=154 Participants	125 Participants n=141 Participants	132 Participants n=157 Participants	120 Participants n=143 Participants	644 Participants n=753 Participants
Race/Ethnicity, Customized Black or African American	17 Participants n=158 Participants	20 Participants n=154 Participants	11 Participants n=141 Participants	20 Participants n=157 Participants	19 Participants n=143 Participants	87 Participants n=753 Participants
Race/Ethnicity, Customized Asian	2 Participants n=158 Participants	0 Participants n=154 Participants	5 Participants n=141 Participants	3 Participants n=157 Participants	2 Participants n=143 Participants	12 Participants n=753 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=158 Participants	0 Participants n=154 Participants	0 Participants n=141 Participants	1 Participants n=157 Participants	1 Participants n=143 Participants	4 Participants n=753 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=158 Participants	3 Participants n=154 Participants	0 Participants n=141 Participants	0 Participants n=157 Participants	1 Participants n=143 Participants	5 Participants n=753 Participants
Race/Ethnicity, Customized Other	0 Participants n=158 Participants	0 Participants n=154 Participants	1 Participants n=141 Participants	1 Participants n=157 Participants	0 Participants n=143 Participants	2 Participants n=753 Participants
Race/Ethnicity, Customized Multiple Races	0 Participants n=158 Participants	0 Participants n=154 Participants	1 Participants n=141 Participants	0 Participants n=157 Participants	0 Participants n=143 Participants	1 Participants n=753 Participants
Acute S-K baseline ≤ 5.3 mmol/L	95 Participants n=158 Participants	76 Participants n=154 Participants	72 Participants n=141 Participants	90 Participants n=157 Participants	94 Participants n=143 Participants	427 Participants n=753 Participants
Acute S-K baseline 5.4-5.5 mmol/L	22 Participants n=158 Participants	38 Participants n=154 Participants	29 Participants n=141 Participants	36 Participants n=157 Participants	27 Participants n=143 Participants	152 Participants n=753 Participants
Acute S-K baseline > 5.5 mmol/L	41 Participants n=158 Participants	40 Participants n=154 Participants	40 Participants n=141 Participants	31 Participants n=157 Participants	22 Participants n=143 Participants	174 Participants n=753 Participants
Etiology of elevated S-K Chronic kidney disease	96 Participants n=158 Participants	102 Participants n=154 Participants	89 Participants n=141 Participants	93 Participants n=157 Participants	83 Participants n=143 Participants	463 Participants n=753 Participants
Etiology of elevated S-K Congestive heart failure	66 Participants n=158 Participants	57 Participants n=154 Participants	54 Participants n=141 Participants	64 Participants n=157 Participants	59 Participants n=143 Participants	300 Participants n=753 Participants
Etiology of elevated S-K Diabetes mellitus	96 Participants n=158 Participants	94 Participants n=154 Participants	84 Participants n=141 Participants	96 Participants n=157 Participants	81 Participants n=143 Participants	451 Participants n=753 Participants
Etiology of elevated S-K RAAS inhibitor medication	101 Participants n=158 Participants	109 Participants n=154 Participants	97 Participants n=141 Participants	99 Participants n=157 Participants	96 Participants n=143 Participants	502 Participants n=753 Participants
Baseline eGFR <15 ml/min	15 Participants n=158 Participants • Subjects with non-missing acute phase baseline eGFR	8 Participants n=151 Participants • Subjects with non-missing acute phase baseline eGFR	15 Participants n=138 Participants • Subjects with non-missing acute phase baseline eGFR	8 Participants n=154 Participants • Subjects with non-missing acute phase baseline eGFR	10 Participants n=143 Participants • Subjects with non-missing acute phase baseline eGFR	56 Participants n=744 Participants • Subjects with non-missing acute phase baseline eGFR
Baseline eGFR 15-29+ ml/min	44 Participants n=158 Participants • Subjects with non-missing acute phase baseline eGFR	42 Participants n=151 Participants • Subjects with non-missing acute phase baseline eGFR	38 Participants n=138 Participants • Subjects with non-missing acute phase baseline eGFR	43 Participants n=154 Participants • Subjects with non-missing acute phase baseline eGFR	42 Participants n=143 Participants • Subjects with non-missing acute phase baseline eGFR	209 Participants n=744 Participants • Subjects with non-missing acute phase baseline eGFR
Baseline eGFR 30-59+ mL/min	61 Participants n=158 Participants • Subjects with non-missing acute phase baseline eGFR	73 Participants n=151 Participants • Subjects with non-missing acute phase baseline eGFR	48 Participants n=138 Participants • Subjects with non-missing acute phase baseline eGFR	64 Participants n=154 Participants • Subjects with non-missing acute phase baseline eGFR	50 Participants n=143 Participants • Subjects with non-missing acute phase baseline eGFR	296 Participants n=744 Participants • Subjects with non-missing acute phase baseline eGFR
Baseline eGFR ≥60 mL/min	38 Participants n=158 Participants • Subjects with non-missing acute phase baseline eGFR	28 Participants n=151 Participants • Subjects with non-missing acute phase baseline eGFR	37 Participants n=138 Participants • Subjects with non-missing acute phase baseline eGFR	39 Participants n=154 Participants • Subjects with non-missing acute phase baseline eGFR	41 Participants n=143 Participants • Subjects with non-missing acute phase baseline eGFR	183 Participants n=744 Participants • Subjects with non-missing acute phase baseline eGFR

PRIMARY outcome

Timeframe: Through 48 hours acute phase

Population: ITT Population

Outcome measures

Outcome measures
Measure	Acute Phase: Placebo TID n=158 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=154 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=141 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=157 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 g TID n=143 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: ZS 5 g QD Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g ( Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Exponential Rate of Change in Serum Potassium (S-K) Levels During the Initial 48 Hours of Study Drug Treatment. Through 24 Hours	-0.00128 log(mmol/L)/hour Standard Error 0.000243	-0.00187 log(mmol/L)/hour Standard Error 0.000250	-0.00205 log(mmol/L)/hour Standard Error 0.000263	-0.00280 log(mmol/L)/hour Standard Error 0.000250	-0.00382 log(mmol/L)/hour Standard Error 0.000258	—	—	—	—	—
Exponential Rate of Change in Serum Potassium (S-K) Levels During the Initial 48 Hours of Study Drug Treatment. Through 48 Hours	-0.00097 log(mmol/L)/hour Standard Error 0.000137	-0.00110 log(mmol/L)/hour Standard Error 0.000141	-0.00163 log(mmol/L)/hour Standard Error 0.000148	-0.00223 log(mmol/L)/hour Standard Error 0.000141	-0.00321 log(mmol/L)/hour Standard Error 0.000145	—	—	—	—	—

PRIMARY outcome

Timeframe: Through 12 days subacute phase (Day 3 through Day 15)

Population: ITT population. One subject in the ZS 5 g TID/5 g QD group died on Study Day 4 and was excluded from the ITT Population

Outcome measures

Outcome measures
Measure	Acute Phase: Placebo TID n=41 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=49 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=46 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=54 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 g TID n=68 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: ZS 5 g QD n=64 Participants Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD n=61 Participants Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD n=63 Participants Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) n=46 Participants Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g ( Acute Phase: Placebo) n=50 Participants Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Exponential Rate of Change in S-K Levels in the Subacute Phase. Through Day 8	0.00054 log(mmol/L)/hour Standard Error 0.004803	0.00874 log(mmol/L)/hour Standard Error 0.004308	0.01104 log(mmol/L)/hour Standard Error 0.004123	0.00734 log(mmol/L)/hour Standard Error 0.003642	0.01441 log(mmol/L)/hour Standard Error 0.003776	0.00581 log(mmol/L)/hour Standard Error 0.003918	0.02469 log(mmol/L)/hour Standard Error 0.003939	-0.00053 log(mmol/L)/hour Standard Error 0.003877	0.00643 log(mmol/L)/hour Standard Error 0.004171	0.00390 log(mmol/L)/hour Standard Error 0.004023
Exponential Rate of Change in S-K Levels in the Subacute Phase. Through Day 15	0.00085 log(mmol/L)/hour Standard Error 0.001089	0.00198 log(mmol/L)/hour Standard Error 0.000959	0.00206 log(mmol/L)/hour Standard Error 0.001189	0.00237 log(mmol/L)/hour Standard Error 0.001049	0.00457 log(mmol/L)/hour Standard Error 0.001007	0.00089 log(mmol/L)/hour Standard Error 0.001049	0.00979 log(mmol/L)/hour Standard Error 0.001115	0.00136 log(mmol/L)/hour Standard Error 0.001097	-0.00098 log(mmol/L)/hour Standard Error 0.001054	0.00023 log(mmol/L)/hour Standard Error 0.001004

SECONDARY outcome

Timeframe: Through 48 hours acute phase

Population: Subjects from ITT population who have completed Acute phase

Outcome measures

Outcome measures
Measure	Acute Phase: Placebo TID n=157 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=150 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=137 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=152 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 g TID n=140 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: ZS 5 g QD Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g ( Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Percentage of Subjects Who Achieve Normalization in S-K Levels After 48 Hours of Treatment	47.8 percentage of participants	51.3 percentage of participants	67.9 percentage of participants	77.6 percentage of participants	86.4 percentage of participants	—	—	—	—	—

SECONDARY outcome

Timeframe: Through 48 hours acute phase. In particular, at Baseline; 1, 2, 4 hour Post 1st Dose on Study Day 1; 0 hour Pre-dose, 1, 4 hour Post 1st Dose on Study Day 2; and 0 hour Pre-dose on Study Day 3.

Population: ITT population

Mean change from baseline in S-K at all time points over initial 48 hours

Outcome measures

Outcome measures
Measure	Acute Phase: Placebo TID n=158 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=154 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=141 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=157 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 g TID n=143 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: ZS 5 g QD Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g ( Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Mean Change From Baseline in S-K at All Time Points Acute Phase Study Day 1: 2 hour Post 1st Dose	0.00 mmol/L Standard Deviation 0.423	-0.04 mmol/L Standard Deviation 0.366	-0.06 mmol/L Standard Deviation 0.499	-0.09 mmol/L Standard Deviation 0.355	-0.18 mmol/L Standard Deviation 0.360	—	—	—	—	—
Mean Change From Baseline in S-K at All Time Points Acute Phase Study Day 1: 4 hour Post 1st Dose	-0.22 mmol/L Standard Deviation 0.429	-0.28 mmol/L Standard Deviation 0.425	-0.34 mmol/L Standard Deviation 0.409	-0.31 mmol/L Standard Deviation 0.389	-0.37 mmol/L Standard Deviation 0.445	—	—	—	—	—
Mean Change From Baseline in S-K at All Time Points Acute Phase Baseline, mean	5.30 mmol/L Standard Deviation 0.365	5.37 mmol/L Standard Deviation 0.369	5.35 mmol/L Standard Deviation 0.400	5.31 mmol/L Standard Deviation 0.337	5.26 mmol/L Standard Deviation 0.337	—	—	—	—	—
Mean Change From Baseline in S-K at All Time Points Acute Phase Study Day 1: 1 hour Post 1st Dose	0.01 mmol/L Standard Deviation 0.404	-0.01 mmol/L Standard Deviation 0.360	-0.08 mmol/L Standard Deviation 0.394	-0.06 mmol/L Standard Deviation 0.413	-0.11 mmol/L Standard Deviation 0.361	—	—	—	—	—
Mean Change From Baseline in S-K at All Time Points Acute Phase Study Day 2: 0 hour Pre-dose	-0.18 mmol/L Standard Deviation 0.363	-0.28 mmol/L Standard Deviation 0.393	-0.32 mmol/L Standard Deviation 0.390	-0.40 mmol/L Standard Deviation 0.375	-0.52 mmol/L Standard Deviation 0.364	—	—	—	—	—
Mean Change From Baseline in S-K at All Time Points Acute Phase Study Day 2: 1 hour Post 1st Dose	-0.24 mmol/L Standard Deviation 0.484	-0.27 mmol/L Standard Deviation 0.415	-0.38 mmol/L Standard Deviation 0.479	-0.46 mmol/L Standard Deviation 0.440	-0.68 mmol/L Standard Deviation 0.437	—	—	—	—	—
Mean Change From Baseline in S-K at All Time Points Acute Phase Study Day 2: 4 hour Post 1st Dose	-0.22 mmol/L Standard Deviation 0.440	-0.32 mmol/L Standard Deviation 0.449	-0.40 mmol/L Standard Deviation 0.462	-0.47 mmol/L Standard Deviation 0.465	-0.62 mmol/L Standard Deviation 0.420	—	—	—	—	—
Mean Change From Baseline in S-K at All Time Points Acute Phase Study Day 3: 0 hour Pre-dose	-0.25 mmol/L Standard Deviation 0.413	-0.30 mmol/L Standard Deviation 0.404	-0.46 mmol/L Standard Deviation 0.398	-0.54 mmol/L Standard Deviation 0.459	-0.73 mmol/L Standard Deviation 0.496	—	—	—	—	—

SECONDARY outcome

Timeframe: Through 48 hours acute phase. In particular, 1, 2, 4 hour Post 1st Dose on Study Day 1; 0 hour Pre-dose, 1, 4 hour Post 1st Dose on Study Day 2; and 0 hour Pre-dose on Study Day 3.

Population: ITT population

Mean percent change from baseline in S-K at all time points over initial 48 hours

Outcome measures

Outcome measures
Measure	Acute Phase: Placebo TID n=158 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=154 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=141 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=157 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 g TID n=143 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: ZS 5 g QD Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g ( Acute Phase: Placebo) Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase Study Day 1: 1 hour Post 1st Dose Percent change	0.09 percentage Standard Deviation 7.606	-0.23 percentage Standard Deviation 6.732	-1.37 percentage Standard Deviation 7.273	-1.13 percentage Standard Deviation 7.791	-2.08 percentage Standard Deviation 6.873	—	—	—	—	—
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase Study Day 1: 2 hour Post 1st Dose Percent change	0.03 percentage Standard Deviation 7.911	-0.81 percentage Standard Deviation 6.813	-0.99 percentage Standard Deviation 9.384	-1.71 percentage Standard Deviation 6.725	-3.43 percentage Standard Deviation 6.779	—	—	—	—	—
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase Study Day 1: 4 hour Post 1st Dose Percent change	-4.05 percentage Standard Deviation 8.021	-5.20 percentage Standard Deviation 7.842	-6.34 percentage Standard Deviation 7.460	-5.74 percentage Standard Deviation 7.283	-6.91 percentage Standard Deviation 8.249	—	—	—	—	—
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase Study Day 2: 0 hour Pre-dose Percent change	-3.40 percentage Standard Deviation 6.819	-5.14 percentage Standard Deviation 7.190	-6.02 percentage Standard Deviation 7.099	-7.31 percentage Standard Deviation 6.942	-9.85 percentage Standard Deviation 6.693	—	—	—	—	—
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase Study Day 2: 1 hour Post 1st Dose Percent change	-4.42 percentage Standard Deviation 8.904	-4.99 percentage Standard Deviation 7.717	-6.95 percentage Standard Deviation 8.910	-8.62 percentage Standard Deviation 8.082	-12.70 percentage Standard Deviation 8.091	—	—	—	—	—
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase Study Day 2: 4 hour Post 1st Dose Percent change	-4.08 percentage Standard Deviation 8.253	-5.82 percentage Standard Deviation 8.187	-7.27 percentage Standard Deviation 8.405	-8.63 percentage Standard Deviation 8.541	-11.58 percentage Standard Deviation 7.645	—	—	—	—	—
Mean Percent Change From Baseline in S-K Change at All Time Points Acute Phase Study Day 3: 0 hour Pre-dose Percent change	-4.62 percentage Standard Deviation 7.751	-5.44 percentage Standard Deviation 7.476	-8.48 percentage Standard Deviation 7.291	-10.04 percentage Standard Deviation 8.33	-13.76 percentage Standard Deviation 9.044	—	—	—	—	—

SECONDARY outcome

Timeframe: Through 18 days (12 days treatment, 6 days follow-up) of subacute phase

Population: ITT population. One subject (087-025) in the ZS 5 g TID/5 g QD group died on Study Day 4 and was excluded from the ITT Population

Time (number of days) subjects remain normokalemic (3.5 - 5.0 mmol/l) subacute phase

Outcome measures

Outcome measures
Measure	Acute Phase: Placebo TID n=41 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=49 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=46 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=54 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 g TID n=68 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: ZS 5 g QD n=64 Participants Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD n=61 Participants Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD n=63 Participants Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) n=46 Participants Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g ( Acute Phase: Placebo) n=50 Participants Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Time Subjects Remain Normokalemic (Subacute Phase)	7.6 Days Standard Deviation 4.71	7.2 Days Standard Deviation 5.08	6.2 Days Standard Deviation 4.78	8.6 Days Standard Deviation 4.55	6.0 Days Standard Deviation 4.43	9.0 Days Standard Deviation 4.22	8.2 Days Standard Deviation 4.64	10.2 Days Standard Deviation 3.96	8.5 Days Standard Deviation 4.57	8.2 Days Standard Deviation 4.72

SECONDARY outcome

Timeframe: Through 18 days of subacute phase (12 days treatment, 6 days follow-up)

Population: ITT population. One subject (087-025) in the ZS 5 g TID/5 g QD group died on Study Day 4 and was excluded from the ITT Population

Percentage of subjects within each treatment group who retained normal S-K values (values between 3.5-5.0 mmol/L) at end of subacute phase

Outcome measures

Outcome measures
Measure	Acute Phase: Placebo TID n=41 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=49 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=46 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=54 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 g TID n=68 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: ZS 5 g QD n=64 Participants Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD n=61 Participants Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD n=63 Participants Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) n=46 Participants Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g ( Acute Phase: Placebo) n=50 Participants Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Percentage of Subjects Within Each Treatment Group Who Retained Normal S-K Values at End of Subacute Phase	73.2 percentage of participants	59.2 percentage of participants	65.2 percentage of participants	64.8 percentage of participants	54.4 percentage of participants	57.8 percentage of participants	60.7 percentage of participants	61.9 percentage of participants	67.4 percentage of participants	66 percentage of participants

SECONDARY outcome

Timeframe: Through 18 days of subacute phase (12 days treatment, 6 days follow-up)

Population: ITT population. One subject (087-025) in the ZS 5 g TID/5 g QD group died on Study Day 4 and was excluded from the ITT Population

Mean change from subacute baseline in serum potassium at all time points during subacute phase

Outcome measures

Outcome measures
Measure	Acute Phase: Placebo TID n=41 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=49 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=46 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=54 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 g TID n=68 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: ZS 5 g QD n=64 Participants Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD n=61 Participants Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD n=63 Participants Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) n=46 Participants Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g ( Acute Phase: Placebo) n=50 Participants Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Mean Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 6	0.11 mmol/L Standard Deviation 0.385	0.07 mmol/L Standard Deviation 0.411	0.22 mmol/L Standard Deviation 0.532	0.12 mmol/L Standard Deviation 0.356	0.27 mmol/L Standard Deviation 0.560	0.11 mmol/L Standard Deviation 0.510	0.43 mmol/L Standard Deviation 0.467	0.10 mmol/L Standard Deviation 0.573	0.04 mmol/L Standard Deviation 0.409	0.13 mmol/L Standard Deviation 0.457
Mean Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 12	0.04 mmol/L Standard Deviation 0.477	0.18 mmol/L Standard Deviation 0.368	0.18 mmol/L Standard Deviation 0.520	0.23 mmol/L Standard Deviation 0.451	0.24 mmol/L Standard Deviation 0.584	0.14 mmol/L Standard Deviation 0.532	0.58 mmol/L Standard Deviation 0.485	0.06 mmol/L Standard Deviation 0.564	-0.01 mmol/L Standard Deviation 0.438	0.04 mmol/L Standard Deviation 0.451
Mean Change From Subacute Baseline in Serum Potassium at All Time Points. Acute Baseline, mean	5.22 mmol/L Standard Deviation 0.263	5.29 mmol/L Standard Deviation 0.343	5.25 mmol/L Standard Deviation 0.268	5.23 mmol/L Standard Deviation 0.354	5.31 mmol/L Standard Deviation 0.302	5.24 mmol/L Standard Deviation 0.325	5.24 mmol/L Standard Deviation 0.290	5.27 mmol/L Standard Deviation 0.369	5.15 mmol/L Standard Deviation 0.293	5.19 mmol/L Standard Deviation 0.325
Mean Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Baseline, mean	4.81 mmol/L Standard Deviation 0.324	4.80 mmol/L Standard Deviation 0.391	4.77 mmol/L Standard Deviation 0.349	4.66 mmol/L Standard Deviation 0.336	4.76 mmol/L Standard Deviation 0.440	4.63 mmol/L Standard Deviation 0.357	4.42 mmol/L Standard Deviation 0.353	4.52 mmol/L Standard Deviation 0.448	4.81 mmol/L Standard Deviation 0.348	4.80 mmol/L Standard Deviation 0.379
Mean Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 1	0.02 mmol/L Standard Deviation 0.362	0.15 mmol/L Standard Deviation 0.416	0.21 mmol/L Standard Deviation 0.416	0.11 mmol/L Standard Deviation 0.329	0.07 mmol/L Standard Deviation 0.493	0.12 mmol/L Standard Deviation 0.446	0.13 mmol/L Standard Deviation 0.363	0.00 mmol/L Standard Deviation 0.452	0.05 mmol/L Standard Deviation 0.373	0.04 mmol/L Standard Deviation 0.362
Mean Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 2	-0.06 mmol/L Standard Deviation 0.575	0.13 mmol/L Standard Deviation 0.405	0.07 mmol/L Standard Deviation 0.451	0.05 mmol/L Standard Deviation 0.360	0.12 mmol/L Standard Deviation 0.477	0.10 mmol/L Standard Deviation 0.519	0.28 mmol/L Standard Deviation 0.387	0.00 mmol/L Standard Deviation 0.531	0.07 mmol/L Standard Deviation 0.437	0.12 mmol/L Standard Deviation 0.389
Mean Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 3	0.04 mmol/L Standard Deviation 0.387	0.11 mmol/L Standard Deviation 0.432	0.17 mmol/L Standard Deviation 0.431	0.18 mmol/L Standard Deviation 0.350	0.17 mmol/L Standard Deviation 0.503	0.11 mmol/L Standard Deviation 0.499	0.37 mmol/L Standard Deviation 0.426	-0.06 mmol/L Standard Deviation 0.557	0.11 mmol/L Standard Deviation 0.400	0.03 mmol/L Standard Deviation 0.501
Mean Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 18	0.06 mmol/L Standard Deviation 0.474	0.22 mmol/L Standard Deviation 0.459	0.09 mmol/L Standard Deviation 0.442	0.18 mmol/L Standard Deviation 0.522	0.26 mmol/L Standard Deviation 0.555	0.30 mmol/L Standard Deviation 0.539	0.59 mmol/L Standard Deviation 0.504	0.44 mmol/L Standard Deviation 0.652	0.09 mmol/L Standard Deviation 0.477	0.14 mmol/L Standard Deviation 0.492

SECONDARY outcome

Timeframe: Through 18 days of subacute phase (12 days treatment, 6 days follow-up)

Population: ITT population. One subject (087-025) in the ZS 5 g TID/5 g QD group died on Study Day 4 and was excluded from the ITT Population

Mean percent change from subacute baseline in serum potassium at all time points during subacute phase

Outcome measures

Outcome measures
Measure	Acute Phase: Placebo TID n=41 Participants Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=49 Participants Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=46 Participants Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=54 Participants Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 g TID n=68 Participants Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: ZS 5 g QD n=64 Participants Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD n=61 Participants Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD n=63 Participants Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 (Acute Phase: Placebo) n=46 Participants Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g ( Acute Phase: Placebo) n=50 Participants Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 1 Percent Change	0.66 percentage Standard Deviation 7.386	3.31 percentage Standard Deviation 8.848	4.74 percentage Standard Deviation 8.819	2.58 percentage Standard Deviation 7.055	2.03 percentage Standard Deviation 9.511	2.90 percentage Standard Deviation 9.738	3.15 percentage Standard Deviation 8.368	0.45 percentage Standard Deviation 9.412	1.26 percentage Standard Deviation 7.859	0.99 percentage Standard Deviation 7.696
Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 2 Percent Change	-1.05 percentage Standard Deviation 12.031	2.79 percentage Standard Deviation 8.465	1.79 percentage Standard Deviation 9.198	1.30 percentage Standard Deviation 7.766	2.96 percentage Standard Deviation 8.913	2.54 percentage Standard Deviation 11.925	6.58 percentage Standard Deviation 8.908	0.67 percentage Standard Deviation 11.555	1.59 percentage Standard Deviation 8.948	2.67 percentage Standard Deviation 8.257
Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 3 Percent Change	1.15 percentage Standard Deviation 7.930	2.56 percentage Standard Deviation 9.098	3.79 percentage Standard Deviation 8.956	4.12 percentage Standard Deviation 7.870	4.15 percentage Standard Deviation 9.464	2.82 percentage Standard Deviation 11.259	8.73 percentage Standard Deviation 9.982	-0.52 percentage Standard Deviation 11.590	2.49 percentage Standard Deviation 8.510	1.12 percentage Standard Deviation 10.533
Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 6 Percent Change	2.46 percentage Standard Deviation 8.048	1.58 percentage Standard Deviation 8.271	4.83 percentage Standard Deviation 10.881	2.90 percentage Standard Deviation 7.769	6.16 percentage Standard Deviation 11.061	2.84 percentage Standard Deviation 11.565	10.22 percentage Standard Deviation 11.027	2.90 percentage Standard Deviation 12.396	1.18 percentage Standard Deviation 8.583	3.05 percentage Standard Deviation 9.397
Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 12 Percent Change	1.13 percentage Standard Deviation 9.955	3.95 percentage Standard Deviation 7.550	4.16 percentage Standard Deviation 10.727	5.33 percentage Standard Deviation 9.976	5.67 percentage Standard Deviation 12.400	3.53 percentage Standard Deviation 11.664	13.52 percentage Standard Deviation 11.493	1.88 percentage Standard Deviation 12.344	0.07 percentage Standard Deviation 9.117	1.10 percentage Standard Deviation 9.679
Mean Percent Change From Subacute Baseline in Serum Potassium at All Time Points. Subacute Day 18 Percent Change	1.56 percentage Standard Deviation 10.145	4.73 percentage Standard Deviation 10.015	2.19 percentage Standard Deviation 9.338	4.35 percentage Standard Deviation 11.587	6.00 percentage Standard Deviation 11.393	7.07 percentage Standard Deviation 11.918	13.80 percentage Standard Deviation 12.182	10.38 percentage Standard Deviation 14.581	1.94 percentage Standard Deviation 10.241	3.01 percentage Standard Deviation 10.301

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Acute Phase: Placebo TID n=158 participants at risk Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=154 participants at risk Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=141 participants at risk Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=157 participants at risk Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 TID n=143 participants at risk Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: Placebo Matched to ZS 1.25g QD n=41 participants at risk Participants who received ZS 1.25 g TID in the acute phase and administered placebo as suspension once daily (QD) for 12 days.	Subacute Phase: ZS 1.25 g QD n=49 participants at risk Participants who received ZS 1.25g TID in the acute phase and administered ZS 1.25 g QD for 12 days.	Subacute Phase: Placebo Matched to ZS 2.5 g QD n=46 participants at risk Participants who received ZS 2.5 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g QD n=54 participants at risk Participants who received ZS 2.5 g TID in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 5 g QD n=68 participants at risk Participants who received ZS 5 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 5 g QD n=65 participants at risk Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD n=61 participants at risk Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD n=63 participants at risk Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 g QD (Acute Phase: Placebo) n=46 participants at risk Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g QD (Acute Phase; Placebo) n=50 participants at risk Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Cardiac disorders Diastolic dysfunction	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
General disorders Chest pain	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
General disorders Malaise	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	2.4% 1/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Infections and infestations Gastroenteritis	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Infections and infestations Nocardiosis	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Infections and infestations Pneumonia	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	2.2% 1/46 • Seven days after the last dose of study medication. 21 days overall	1.9% 1/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Infections and infestations Urinary tract infection	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	1.9% 1/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Investigations Blood potassium increased	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Metabolism and nutrition disorders Gout	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Nervous system disorders Loss of consciousness	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Renal and urinary disorders Renal failure	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Renal and urinary disorders Renal failure acute	0.63% 1/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Renal and urinary disorders Urinary retention	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	2.2% 1/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/50 • Seven days after the last dose of study medication. 21 days overall
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Surgical and medical procedures Hospitalization	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Cardiac disorders Cardiac failure congestive	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall

Other adverse events

Other adverse events
Measure	Acute Phase: Placebo TID n=158 participants at risk Participants administered placebo three times daily (TID) orally as suspension for first 48 hours.	Acute Phase: Sodium Zirconium Cyclosilicate (ZS) 1.25 g TID n=154 participants at risk Participants administered ZS 1.25 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 2.5 g TID n=141 participants at risk Participants administered ZS 2.5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 5 g TID n=157 participants at risk Participants administered ZS 5 g TID as suspension orally for first 48 hours.	Acute Phase: ZS 10 TID n=143 participants at risk Participants administered ZS 10 g TID as suspension orally for first 48 hours.	Subacute Phase: Placebo Matched to ZS 1.25g QD n=41 participants at risk Participants who received ZS 1.25 g TID in the acute phase and administered placebo as suspension once daily (QD) for 12 days.	Subacute Phase: ZS 1.25 g QD n=49 participants at risk Participants who received ZS 1.25g TID in the acute phase and administered ZS 1.25 g QD for 12 days.	Subacute Phase: Placebo Matched to ZS 2.5 g QD n=46 participants at risk Participants who received ZS 2.5 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g QD n=54 participants at risk Participants who received ZS 2.5 g TID in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 5 g QD n=68 participants at risk Participants who received ZS 5 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 5 g QD n=65 participants at risk Participants who received ZS 5 g TID in the acute phase and administered ZS 5 g as suspension QD for 12 days.	Subacute Phase: Placebo Matched to ZS 10 g QD n=61 participants at risk Participants who received ZS 10 g TID in the acute phase and administered placebo as suspension QD for 12 days.	Subacute Phase: ZS 10 g QD n=63 participants at risk Participants who received ZS 10 g TID in the acute phase and administered ZS 10 g QD as suspension for 12 days.	Subacute Phase: ZS 1.25 g QD (Acute Phase: Placebo) n=46 participants at risk Participants who received placebo in the acute phase and administered ZS 1.25 g as suspension QD for 12 days.	Subacute Phase: ZS 2.5 g QD (Acute Phase; Placebo) n=50 participants at risk Participants who received placebo in the acute phase and administered ZS 2.5 g as suspension QD for 12 days.
Gastrointestinal disorders Vomiting	1.3% 2/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.70% 1/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	2.2% 1/46 • Seven days after the last dose of study medication. 21 days overall	3.7% 2/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	4.6% 3/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
General disorders Malaise	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	2.4% 1/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
General disorders Oedema peripheral	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.65% 1/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	1.4% 2/143 • Seven days after the last dose of study medication. 21 days overall	2.4% 1/41 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	2.9% 2/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	3.2% 2/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	4.0% 2/50 • Seven days after the last dose of study medication. 21 days overall
Infections and infestations Pneumonia	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	2.2% 1/46 • Seven days after the last dose of study medication. 21 days overall	1.9% 1/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Infections and infestations Streptococcal urinary tract infection	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	4.0% 2/50 • Seven days after the last dose of study medication. 21 days overall
Infections and infestations Upper respiratory tract infection	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	2.4% 1/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Infections and infestations Urinary tract infection	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	3.2% 5/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.64% 1/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	9.8% 4/41 • Seven days after the last dose of study medication. 21 days overall	8.2% 4/49 • Seven days after the last dose of study medication. 21 days overall	2.2% 1/46 • Seven days after the last dose of study medication. 21 days overall	5.6% 3/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	7.7% 5/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	6.3% 4/63 • Seven days after the last dose of study medication. 21 days overall	6.5% 3/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Infections and infestations Urinary tract infection, bacterial	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/68 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Injury, poisoning and procedural complications Laceration	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	2.4% 1/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Investigations Blood glucose decreased	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.65% 1/154 • Seven days after the last dose of study medication. 21 days overall	0.71% 1/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.70% 1/143 • Seven days after the last dose of study medication. 21 days overall	2.4% 1/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	1.9% 1/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Investigations Blood potassium increased	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/68 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Investigations Transaminases increased	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.71% 1/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.70% 1/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	1.9% 1/54 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Renal and urinary disorders Haematuria	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	2.4% 1/41 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Renal and urinary disorders Renal failure acute	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	1.9% 1/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Renal and urinary disorders Renal impairment	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	2.4% 1/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Cardiac disorders Atrial fibrilliation	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Gastrointestinal disorders Constipation	0.63% 1/158 • Seven days after the last dose of study medication. 21 days overall	0.65% 1/154 • Seven days after the last dose of study medication. 21 days overall	0.71% 1/141 • Seven days after the last dose of study medication. 21 days overall	0.64% 1/157 • Seven days after the last dose of study medication. 21 days overall	2.1% 3/143 • Seven days after the last dose of study medication. 21 days overall	2.4% 1/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	3.2% 2/63 • Seven days after the last dose of study medication. 21 days overall	4.3% 2/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Gastrointestinal disorders Diarrhoea	2.5% 4/158 • Seven days after the last dose of study medication. 21 days overall	3.2% 5/154 • Seven days after the last dose of study medication. 21 days overall	1.4% 2/141 • Seven days after the last dose of study medication. 21 days overall	1.9% 3/157 • Seven days after the last dose of study medication. 21 days overall	0.70% 1/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	4.3% 2/46 • Seven days after the last dose of study medication. 21 days overall	3.7% 2/54 • Seven days after the last dose of study medication. 21 days overall	4.4% 3/68 • Seven days after the last dose of study medication. 21 days overall	3.1% 2/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	4.0% 2/50 • Seven days after the last dose of study medication. 21 days overall
Gastrointestinal disorders Dyspepsia	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	3.1% 2/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Gastrointestinal disorders Nausea	0.63% 1/158 • Seven days after the last dose of study medication. 21 days overall	1.3% 2/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.64% 1/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	2.2% 1/46 • Seven days after the last dose of study medication. 21 days overall	3.7% 2/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/63 • Seven days after the last dose of study medication. 21 days overall	6.5% 3/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	4.9% 2/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Respiratory, thoracic and mediastinal disorders Cough	0.63% 1/158 • Seven days after the last dose of study medication. 21 days overall	0.65% 1/154 • Seven days after the last dose of study medication. 21 days overall	0.71% 1/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/49 • Seven days after the last dose of study medication. 21 days overall	2.2% 1/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	2.0% 1/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/61 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall
Vascular disorders Hypertension	0.00% 0/158 • Seven days after the last dose of study medication. 21 days overall	1.3% 2/154 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/141 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/157 • Seven days after the last dose of study medication. 21 days overall	0.70% 1/143 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/41 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/49 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/54 • Seven days after the last dose of study medication. 21 days overall	1.5% 1/68 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/65 • Seven days after the last dose of study medication. 21 days overall	3.3% 2/61 • Seven days after the last dose of study medication. 21 days overall	1.6% 1/63 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/46 • Seven days after the last dose of study medication. 21 days overall	0.00% 0/50 • Seven days after the last dose of study medication. 21 days overall

Additional Information

AstraZeneca Clinical Study Information Center

ZS Pharma, Inc.

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee ZS Pharma has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
Publication restrictions are in place

Restriction type: OTHER