Trial Outcomes & Findings for Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia. (NCT NCT02088073)

NCT ID: NCT02088073

Last Updated: 2018-12-07

Results Overview

The least squares means (LSMeans) are dervied from a mixed effects model of serial log transformed S-K values between Days 8 and 29 with patients as a random effect and the following fixed effects terms: MP treatment group; AP baseline eGFR; AP and MP baseline S-K levels, age categories (\<55, 55-64, \>= 65 years); and binary indicators for RAAS inhibitors use, CKD, CHF, and DM. The LSmeans estimate obtained from the above model is back-transformed and presented as the lsmeans of all available S-K values during the Maintenance phase study Days 8 to 29.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

258 participants

Primary outcome timeframe

22 Days; Maintenance Phase Days 8 - 29, inclusive.

Results posted on

2018-12-07

Participant Flow

Participants took part in the study at 44 sites in the United States, Australia, and South Africa from 31 March 2014 to 08 August 2014

Subjects with hyperkalemia (i-STAT potassium value ≥ 5.1 mmol/L) were enrolled in the Acute Phase (AP) and were to be treated with ZS 10 g TID for the 48 hours.Subjects who achieved normokalemia during the AP were randomized to 1 of 3 doses of ZS (5 g, 10 g,or 15 g) or placebo for a further 28 days (Maintenance Phase \[MP\]).

Participant milestones

Participant milestones
Measure	ZS 10 g Three Times Daily (Acute Phase) Sodium zirconium cyclosilicate (ZS) 10 g, three times daily (TID), orally as a suspension for 48 hours.	Placebo Comparator (Maintenance Phase) Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Acute Phase STARTED	258	0	0	0	0
Acute Phase COMPLETED	251	0	0	0	0
Acute Phase NOT COMPLETED	7	0	0	0	0
Maintanance Phase STARTED	0	85	45	51	56
Maintanance Phase COMPLETED	0	75	40	44	49
Maintanance Phase NOT COMPLETED	0	10	5	7	7

Reasons for withdrawal

Reasons for withdrawal
Measure	ZS 10 g Three Times Daily (Acute Phase) Sodium zirconium cyclosilicate (ZS) 10 g, three times daily (TID), orally as a suspension for 48 hours.	Placebo Comparator (Maintenance Phase) Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Acute Phase Withdrawal by Subject	5	0	0	0	0
Acute Phase Hyperkalemia	2	0	0	0	0
Maintanance Phase Withdrawal by Subject	0	2	0	0	0
Maintanance Phase Adverse Event	0	0	3	0	1
Maintanance Phase Physician Decision	0	0	0	0	1
Maintanance Phase Sponsor's decision	0	2	0	2	1
Maintanance Phase Hypo- or hyperkalemia	0	3	0	3	1
Maintanance Phase Miscellaneous	0	2	1	2	1
Maintanance Phase Met ECG withdrawal criteria	0	0	1	0	2
Maintanance Phase Subject compliance	0	1	0	0	0

Baseline Characteristics

Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ZS 10 g Three Times Daily (Acute Phase) n=258 Participants Sodium zirconium cyclosilicate (ZS) 10 g, three times daily (TID), orally as a suspension for 48 hours.	Placebo Comparator (Maintenance Phase) n=85 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=51 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=56 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.	Total n=495 Participants Total of all reporting groups
Age, Continuous Acute Phase	64.0 Years STANDARD_DEVIATION 12.72 • n=5 Participants	NA Years STANDARD_DEVIATION NA • n=7 Participants	NA Years STANDARD_DEVIATION NA • n=5 Participants	NA Years STANDARD_DEVIATION NA • n=4 Participants	NA Years STANDARD_DEVIATION NA • n=21 Participants	64.0 Years STANDARD_DEVIATION 12.72 • n=8 Participants
Age, Continuous Maintenance Phase	NA Years STANDARD_DEVIATION NA • n=5 Participants	64.3 Years STANDARD_DEVIATION 12.13 • n=7 Participants	61.5 Years STANDARD_DEVIATION 16.89 • n=5 Participants	63.8 Years STANDARD_DEVIATION 9.97 • n=4 Participants	64.9 Years STANDARD_DEVIATION 12.85 • n=21 Participants	63.80 Years STANDARD_DEVIATION 13.01 • n=8 Participants
Sex/Gender, Customized Female, Acute Phase	109 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	109 Participants n=8 Participants
Sex/Gender, Customized Male, Acute Phase	149 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	149 Participants n=8 Participants
Sex/Gender, Customized Female, Maintenance Phase	0 Participants n=5 Participants	41 Participants n=7 Participants	18 Participants n=5 Participants	24 Participants n=4 Participants	16 Participants n=21 Participants	99 Participants n=8 Participants
Sex/Gender, Customized Male, Maintenance Phase	0 Participants n=5 Participants	44 Participants n=7 Participants	27 Participants n=5 Participants	27 Participants n=4 Participants	40 Participants n=21 Participants	138 Participants n=8 Participants
Race/Ethnicity, Customized White, Acute Phase	215 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	215 Participants n=8 Participants
Race/Ethnicity, Customized Black or African American, Acute Phase	37 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	37 Participants n=8 Participants
Race/Ethnicity, Customized Asian, Acute Phase	5 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=8 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander, AP	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race/Ethnicity, Customized Other, Acute Phase	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants
Race/Ethnicity, Customized Multiple Races indicated, Acute Phase	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race/Ethnicity, Customized White, Maintenance Phase	0 Participants n=5 Participants	73 Participants n=7 Participants	36 Participants n=5 Participants	44 Participants n=4 Participants	46 Participants n=21 Participants	199 Participants n=8 Participants
Race/Ethnicity, Customized Black or African American, Maintenance Phase	0 Participants n=5 Participants	10 Participants n=7 Participants	8 Participants n=5 Participants	5 Participants n=4 Participants	9 Participants n=21 Participants	32 Participants n=8 Participants
Race/Ethnicity, Customized Asian, Maintenance Phase	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	5 Participants n=8 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander, MP	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race/Ethnicity, Customized Other, Maintenance Phase	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants
Race/Ethnicity, Customized Multiple Races indicated, Maintenance Phase	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases <5.5 mmol/L, Acute Phase	119 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	119 Participants n=8 Participants
Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases 5.5-<6.0 mmol/L, Acute Phase	100 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	100 Participants n=8 Participants
Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases ≥ 6.0 mmol/L, Acute Phase	39 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	39 Participants n=8 Participants
Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases <5.5 mmol/L, Maintenance Phase	0 Participants n=5 Participants	43 Participants n=7 Participants	23 Participants n=5 Participants	19 Participants n=4 Participants	24 Participants n=21 Participants	109 Participants n=8 Participants
Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases 5.5-<6.0 mmol/L, Maintenance Phase	0 Participants n=5 Participants	30 Participants n=7 Participants	17 Participants n=5 Participants	23 Participants n=4 Participants	26 Participants n=21 Participants	96 Participants n=8 Participants
Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases ≥ 6.0 mmol/L, Maintenance Phase	0 Participants n=5 Participants	12 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants	6 Participants n=21 Participants	32 Participants n=8 Participants
eGFR at baseline during both the Acute and Maintenance phases <60 mL/min, Acute Phase	179 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	179 Participants n=8 Participants
eGFR at baseline during both the Acute and Maintenance phases ≥ 60 mL/min, Acute Phase	72 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	72 Participants n=8 Participants
eGFR at baseline during both the Acute and Maintenance phases Not reported, Acute Phase	7 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	7 Participants n=8 Participants
eGFR at baseline during both the Acute and Maintenance phases <60 mL/min, Maintenance Phase	0 Participants n=5 Participants	52 Participants n=7 Participants	31 Participants n=5 Participants	38 Participants n=4 Participants	41 Participants n=21 Participants	162 Participants n=8 Participants
eGFR at baseline during both the Acute and Maintenance phases ≥ 60 mL/min, Maintenance Phase	0 Participants n=5 Participants	28 Participants n=7 Participants	12 Participants n=5 Participants	13 Participants n=4 Participants	15 Participants n=21 Participants	68 Participants n=8 Participants
eGFR at baseline during both the Acute and Maintenance phases Not reported, Maintenance Phase	0 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	7 Participants n=8 Participants
Etiology of elevated S-K levels during both the Acute and Maintenance phases RAAS inhibitor medication, Acute Phase	180 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	180 Participants n=8 Participants
Etiology of elevated S-K levels during both the Acute and Maintenance phases Diabetes mellitus, Acute Phase	170 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	170 Participants n=8 Participants
Etiology of elevated S-K levels during both the Acute and Maintenance phases Chronic kidney disease, Acute Phase	169 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	169 Participants n=8 Participants
Etiology of elevated S-K levels during both the Acute and Maintenance phases Heart failure, Acute Phase	94 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	94 Participants n=8 Participants
Etiology of elevated S-K levels during both the Acute and Maintenance phases RAAS inhibitor medication, Maintenance Phase	0 Participants n=5 Participants	61 Participants n=7 Participants	33 Participants n=5 Participants	36 Participants n=4 Participants	33 Participants n=21 Participants	163 Participants n=8 Participants
Etiology of elevated S-K levels during both the Acute and Maintenance phases Diabetes mellitus, Maintenance Phase	0 Participants n=5 Participants	54 Participants n=7 Participants	26 Participants n=5 Participants	38 Participants n=4 Participants	39 Participants n=21 Participants	157 Participants n=8 Participants
Etiology of elevated S-K levels during both the Acute and Maintenance phases Chronic kidney disease, Maintenance Phase	0 Participants n=5 Participants	50 Participants n=7 Participants	29 Participants n=5 Participants	36 Participants n=4 Participants	37 Participants n=21 Participants	152 Participants n=8 Participants
Etiology of elevated S-K levels during both the Acute and Maintenance phases Heart failure, Maintenance Phase	0 Participants n=5 Participants	26 Participants n=7 Participants	18 Participants n=5 Participants	18 Participants n=4 Participants	25 Participants n=21 Participants	87 Participants n=8 Participants

PRIMARY outcome

Timeframe: 22 Days; Maintenance Phase Days 8 - 29, inclusive.

Population: Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized patients who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population).	5.0603 mmol/L Interval 4.9646 to 5.1578	4.7544 mmol/L Interval 4.635 to 4.8769	4.5081 mmol/L Interval 4.4005 to 4.6184	4.3742 mmol/L Interval 4.2754 to 4.4753

SECONDARY outcome

Timeframe: 22 days; Maintenance Phase Day 8 - 29, inclusive.

The number of normokalemic days during the Maintenance Phase Study Days 8 to 29 is calculated assuming that the interval between assessments is normokalemic only if both the beginning and end assessments for that time interval display normal S-K values (i.e. 3.5 - 5.0 mmol/L)

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT).	7.4 Days Standard Deviation 8.0	13.4 Days Standard Deviation 7.57	13.9 Days Standard Deviation 7.91	16.8 Days Standard Deviation 6.99

SECONDARY outcome

Timeframe: Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.

Population: Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . AP Baseline S-K level	5.55 mmol/L Standard Deviation 0.471	5.53 mmol/L Standard Deviation 0.357	5.58 mmol/L Standard Deviation 0.423	5.55 mmol/L Standard Deviation 0.331
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . MP Study Day 2 Mean Change	-0.86 mmol/L Standard Deviation 0.508	-1.03 mmol/L Standard Deviation 0.408	-1.25 mmol/L Standard Deviation 0.471	-1.12 mmol/L Standard Deviation 0.477
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . MP Study Day 8 Mean Change	-0.49 mmol/L Standard Deviation 0.549	-0.72 mmol/L Standard Deviation 0.552	-1.09 mmol/L Standard Deviation 0.629	-1.20 mmol/L Standard Deviation 0.592
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . MP Study Day 12 Mean Change	-0.41 mmol/L Standard Deviation 0.508	-0.75 mmol/L Standard Deviation 0.516	-1.11 mmol/L Standard Deviation 0.663	-1.20 mmol/L Standard Deviation 0.665
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . MP Study Day 15 Mean Change	-0.48 mmol/L Standard Deviation 0.612	-0.77 mmol/L Standard Deviation 0.492	-1.11 mmol/L Standard Deviation 0.652	-1.19 mmol/L Standard Deviation 0.627
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . MP Study Day 19 Mean Change	-0.45 mmol/L Standard Deviation 0.549	-0.79 mmol/L Standard Deviation 0.520	-1.04 mmol/L Standard Deviation 0.581	-1.07 mmol/L Standard Deviation 0.575
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . MP Study Day 22 Mean Change	-0.45 mmol/L Standard Deviation 0.578	-0.71 mmol/L Standard Deviation 0.543	-0.93 mmol/L Standard Deviation 0.653	-1.05 mmol/L Standard Deviation 0.586
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . MP Study Day 26 Mean Change	-0.43 mmol/L Standard Deviation 0.552	-0.65 mmol/L Standard Deviation 0.448	-0.87 mmol/L Standard Deviation 0.697	-1.03 mmol/L Standard Deviation 0.597
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . MP Study Day 29 Mean Change	-0.47 mmol/L Standard Deviation 0.499	-0.69 mmol/L Standard Deviation 0.500	-1.08 mmol/L Standard Deviation 0.704	-1.12 mmol/L Standard Deviation 0.571
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . MP Study Day 29/Exit Mean Change	-0.44 mmol/L Standard Deviation 0.515	-0.77 mmol/L Standard Deviation 0.559	-1.10 mmol/L Standard Deviation 0.813	-1.19 mmol/L Standard Deviation 0.659

SECONDARY outcome

Timeframe: Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . MP Study Day 15 Percent Change	-8.28 Percent Change Standard Deviation 10.739	-13.73 Percent Change Standard Deviation 8.485	-19.33 Percent Change Standard Deviation 10.884	-21.19 Percent Change Standard Deviation 10.675
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . MP Study Day 19 Percent Change	-7.87 Percent Change Standard Deviation 9.554	-14.08 Percent Change Standard Deviation 8.822	-18.29 Percent Change Standard Deviation 9.707	-19.10 Percent Change Standard Deviation 9.957
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . MP Study Day 2 Percent Change	-15.11 Percent Change Standard Deviation 8.154	-18.53 Percent Change Standard Deviation 6.941	-22.19 Percent Change Standard Deviation 7.897	-20.04 Percent Change Standard Deviation 7.959
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . MP Study Day 8 Percent Change	-8.45 Percent Change Standard Deviation 9.492	-12.84 Percent Change Standard Deviation 9.700	-19.16 Percent Change Standard Deviation 10.708	-21.29 Percent Change Standard Deviation 10.135
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . MP Study Day 12 Percent Change	-7.22 Percent Change Standard Deviation 8.967	-13.36 Percent Change Standard Deviation 8.949	-19.45 Percent Change Standard Deviation 11.072	-21.22 Percent Change Standard Deviation 11.368
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . MP Study Day 22 Percent Change	-7.74 Percent Change Standard Deviation 9.992	-12.65 Percent Change Standard Deviation 9.591	-16.25 Percent Change Standard Deviation 11.292	-18.65 Percent Change Standard Deviation 10.034
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . MP Study Day 26 Percent Change	-7.54 Percent Change Standard Deviation 9.386	-11.83 Percent Change Standard Deviation 8.025	-15.18 Percent Change Standard Deviation 11.988	-18.28 Percent Change Standard Deviation 10.271
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . MP Study Day 29 Percent Change	-8.23 Percent Change Standard Deviation 8.586	-12.49 Percent Change Standard Deviation 8.770	-18.83 Percent Change Standard Deviation 11.951	-19.80 Percent Change Standard Deviation 9.503
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . MP Study Day 29/Exit Percent Change	-7.68 Percent Change Standard Deviation 8.940	-13.85 Percent Change Standard Deviation 9.568	-19.28 Percent Change Standard Deviation 14.099	-21.06 Percent Change Standard Deviation 11.086

SECONDARY outcome

Timeframe: Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 2 Mean change	0.13 mmol/L Standard Deviation 0.411	-0.01 mmol/L Standard Deviation 0.372	-0.04 mmol/L Standard Deviation 0.384	-0.02 mmol/L Standard Deviation 0.400
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 8 Mean change	0.50 mmol/L Standard Deviation 0.538	0.30 mmol/L Standard Deviation 0.467	0.12 mmol/L Standard Deviation 0.523	-0.10 mmol/L Standard Deviation 0.535
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Baseline S-K level	4.55 mmol/L Standard Deviation 0.427	4.51 mmol/L Standard Deviation 0.357	4.38 mmol/L Standard Deviation 0.407	4.45 mmol/L Standard Deviation 0.372
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 12 Mean change	0.60 mmol/L Standard Deviation 0.580	0.26 mmol/L Standard Deviation 0.541	0.10 mmol/L Standard Deviation 0.594	-0.11 mmol/L Standard Deviation 0.572
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 15 Mean change	0.54 mmol/L Standard Deviation 0.694	0.25 mmol/L Standard Deviation 0.535	0.11 mmol/L Standard Deviation 0.552	-0.10 mmol/L Standard Deviation 0.546
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 19 Mean change	0.55 mmol/L Standard Deviation 0.672	0.22 mmol/L Standard Deviation 0.580	0.17 mmol/L Standard Deviation 0.483	0.01 mmol/L Standard Deviation 0.605
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 22 Mean change	0.55 mmol/L Standard Deviation 0.627	0.30 mmol/L Standard Deviation 0.563	0.27 mmol/L Standard Deviation 0.650	0.03 mmol/L Standard Deviation 0.579
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 26 Mean change	0.55 mmol/L Standard Deviation 0.623	0.34 mmol/L Standard Deviation 0.565	0.33 mmol/L Standard Deviation 0.673	0.05 mmol/L Standard Deviation 0.594
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 29 Mean change	0.52 mmol/L Standard Deviation 0.545	0.28 mmol/L Standard Deviation 0.664	0.14 mmol/L Standard Deviation 0.668	-0.04 mmol/L Standard Deviation 0.554
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 29/Exit Mean change	0.56 mmol/L Standard Deviation 0.582	0.25 mmol/L Standard Deviation 0.645	0.11 mmol/L Standard Deviation 0.768	-0.09 mmol/L Standard Deviation 0.598

SECONDARY outcome

Timeframe: Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 15 Percent change	12.51 Percent Change Standard Deviation 15.693	5.95 Percent Change Standard Deviation 12.169	2.93 Percent Change Standard Deviation 12.662	-1.89 Percent Change Standard Deviation 12.118
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 19 Percent change	12.96 Percent Change Standard Deviation 15.791	5.33 Percent Change Standard Deviation 12.934	4.28 Percent Change Standard Deviation 11.231	.095 Percent Change Standard Deviation 13.697
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 29 Percent change	12.09 Percent Change Standard Deviation 13.116	6.12 Percent Change Standard Deviation 14.424	3.02 Percent Change Standard Deviation 17.785	-1.43 Percent Change Standard Deviation 13.664
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 29/Exit Percent change	12.97 Percent Change Standard Deviation 13.116	6.12 Percent Change Standard Deviation 14.424	3.02 Percent Change Standard Deviation 17.785	-1.43 Percent Change Standard Deviation 13.664
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 2 Percent change	3.39 Percent Change Standard Deviation 9.044	0.06 Percent Change Standard Deviation 8.036	-0.51 Percent Change Standard Deviation 8.862	-0.20 Percent Change Standard Deviation 8.984
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 8 Percent change	11.64 Percent Change Standard Deviation 12.291	6.93 Percent Change Standard Deviation 10.486	3.05 Percent Change Standard Deviation 12.346	-1.74 Percent Change Standard Deviation 12.043
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 12 Percent change	13.70 Percent Change Standard Deviation 13.072	6.38 Percent Change Standard Deviation 12.287	2.85 Percent Change Standard Deviation 13.595	-2.00 Percent Change Standard Deviation 12.836
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 22 Percent change	12.84 Percent Change Standard Deviation 14.342	6.98 Percent Change Standard Deviation 12.774	6.79 Percent Change Standard Deviation 15.174	1.39 Percent Change Standard Deviation 12.782
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. MP Study Day 26 Percent change	13.03 Percent Change Standard Deviation 14.566	7.98 Percent Change Standard Deviation 12.932	8.08 Percent Change Standard Deviation 15.516	1.88 Percent Change Standard Deviation 16.641

SECONDARY outcome

Timeframe: Maintenance Phase baseline to maintenance Phase Study Day 29/Exit.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L)	7 Days Interval 6.0 to 7.0	14 Days Interval 7.0 to 28.0	NA Days The Median time was not reached in the ZS 10 g group because fewer than 50% of patients in the group had a hyperkalemic event before the end of the Maintenance Phase.	NA Days The Median time was not reached in the ZS 15 g group because fewer than 50% of patients in the group had a hyperkalemic event before the end of the Maintenance Phase.

SECONDARY outcome

Timeframe: 22 days; Maintenance Phase Day 8 - 29

Population: Maintenance Phase Intent- to-Treat (ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Day 8.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8	0.06392 mmol/L Interval 0.05804 to 0.0698	0.06367 mmol/L Interval 0.05574 to 0.07159	0.07708 mmol/L Interval 0.06941 to 0.08474	0.06849 mmol/L Interval 0.06126 to 0.07571

SECONDARY outcome

Timeframe: Maintenance Phase Study Days 1, 2, 5, 8, 12, 15, 19, 22, 26, 29, and 35, inclusive.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase MP Study Day 26	0.486 Proportion of subjects	0.738 Proportion of subjects	0.711 Proportion of subjects	0.843 Proportion of subjects
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase MP Study Day 29	0.507 Proportion of subjects	0.667 Proportion of subjects	0.816 Proportion of subjects	0.907 Proportion of subjects
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase Baseline	0.866 Proportion of subjects	0.933 Proportion of subjects	0.920 Proportion of subjects	0.926 Proportion of subjects
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase MP Study Day 2	0.84 Proportion of subjects	0.933 Proportion of subjects	0.918 Proportion of subjects	0.944 Proportion of subjects
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase MP Study Day 8	0.481 Proportion of subjects	0.711 Proportion of subjects	0.820 Proportion of subjects	0.852 Proportion of subjects
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase MP Study Day 12	0.400 Proportion of subjects	0.750 Proportion of subjects	0.787 Proportion of subjects	0.849 Proportion of subjects
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase MP Study Day 15	0.438 Proportion of subjects	0.705 Proportion of subjects	0.851 Proportion of subjects	0.827 Proportion of subjects
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase MP Study Day 19	0.449 Proportion of subjects	0.744 Proportion of subjects	0.787 Proportion of subjects	0.882 Proportion of subjects
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase MP Study Day 22	0.442 Proportion of subjects	0.674 Proportion of subjects	0.667 Proportion of subjects	0.882 Proportion of subjects
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase MP Study Day 29/Exit	0.476 Proportion of subjects	0.711 Proportion of subjects	0.760 Proportion of subjects	0.852 Proportion of subjects

SECONDARY outcome

Timeframe: Maintenance phase Study Day 1 to Study Day 29/Exit.

Median time to relapse in S-K values (return to original Acute Phase S-K baseline value)

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=82 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 Participants Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=50 Participants Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=54 Participants Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Median Time to Relapse in S-K Values	19 Days Interval 12.0 to 28.0	29 Days Interval 29.0 to The confidence interval for the median is based on when the lower and upper limits of the confidence interval for survival function reach 50%. However, the upper limit for survival function in the ZS 5 g QD did not reach 50% in the Maintenance Phase.	NA Days Fewer than 50% of patients in the ZS 10 g QD had relapsed at the end of the Maintenance Phase. Therefore, median was not reached.	NA Days Fewer than 50% of patients in the ZS 15 g QD had relapsed at the end of the Maintenance Phase. Therefore, median was not reached.

SECONDARY outcome

Timeframe: Acute Phase 24 hours and Acute Phase 48 hours.

Population: Acute Phase ITT Population included all subjects who received at least 1 Acute Phase dose and had any post-baseline S-K levels after receiving the investigational product during the first 48 hours.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=258 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Exponential Rate of Change in S-K Values During the Acute Phase at 24 Hours and 48 Hours of Study Drug Treatment. 24 hours after start of ZS dosing	-0.00373 log(mmol/L/hour) Standard Error 0.000231	—	—	—
Exponential Rate of Change in S-K Values During the Acute Phase at 24 Hours and 48 Hours of Study Drug Treatment. 48 hours of start of ZS dosing	-0.00324 log(mmol/L/hour) Standard Error 0.000130	—	—	—

SECONDARY outcome

Timeframe: All measured time intervals post dose during the Acute Phase.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=258 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. Acute phase baseline	5.55 mmol/L Standard Deviation 0.449	—	—	—
Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 1 hour after start of ZS dosing Mean change	-0.23 mmol/L Standard Deviation 0.435	—	—	—
Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 2 hours after start of ZS dosing Mean change	-0.41 mmol/L Standard Deviation 0.440	—	—	—
Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 4 hours after start of ZS dosing Mean change	-0.51 mmol/L Standard Deviation 0.405	—	—	—
Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 24 hours after start of ZS dosing Mean change	-0.68 mmol/L Standard Deviation 0.448	—	—	—
Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 1 hour after 1st dose Study Day 2 Mean change	-0.75 mmol/L Standard Deviation 0.444	—	—	—
Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 48 hours after start of ZS dosing Mean change	-1.05 mmol/L Standard Deviation 0.510	—	—	—

SECONDARY outcome

Timeframe: All measured time intervals post dose during the Acute Phase.

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=258 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 1 hour after start of ZS dosing Percent change	-3.91 Percent Change Standard Deviation 7.741	—	—	—
Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 2 hours after start of ZS dosing Percent change	-7.13 Percent Change Standard Deviation 7.706	—	—	—
Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 4 hours after start of ZS dosing Percent change	-9.00 Percent Change Standard Deviation 7.123	—	—	—
Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 24 hours after start of ZS dosing Percent change	-12.03 Percent Change Standard Deviation 7.808	—	—	—
Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 1 hour after 1st dose Study Day 2 Percent change	-13.41 Percent Change Standard Deviation 7.720	—	—	—
Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. 48 hours after start of ZS dosing Percent change	-18.56 Percent Change Standard Deviation 8.506	—	—	—

SECONDARY outcome

Timeframe: Through 48 hours acute phase

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=258 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Proportion of Subjects Who Achieve Normokalemia During the Acute Phase at 24 and 48 Hours After Start of Dosing 24 hours after start of dosing	0.661 Proportion of subjects	—	—	—
Proportion of Subjects Who Achieve Normokalemia During the Acute Phase at 24 and 48 Hours After Start of Dosing 48 hours after of start dosing	0.88 Proportion of subjects	—	—	—

SECONDARY outcome

Timeframe: Through 48 hours acute phase

Outcome measures

Outcome measures
Measure	Placebo Comparator (Maintenance Phase) n=258 Participants Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Median Time to Normalization (3.50-5.0 mmol/L) in S-K Levels in the 48 Hours of Initial Treatment	2.17 Hours Interval 2.0 to 3.97	—	—	—

Adverse Events

ZS 10 g TID (Acute Phase)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo Comparator (Maintenance Phase)

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

ZS 5 g Once Daily (Maintenance Phase)

Serious events: 5 serious events

Other events: 20 other events

Deaths: 0 deaths

ZS 10 g Once Daily (Maintenance Phase)

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

ZS 15 g Once Daily (Maintenance Phase)

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ZS 10 g TID (Acute Phase) n=258 participants at risk ZS (sodium zirconium cyclosilicate) 10 g, three times a day, orally as suspension in water for 48 hours.	Placebo Comparator (Maintenance Phase) n=85 participants at risk Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 participants at risk Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=51 participants at risk Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=56 participants at risk Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Cardiac disorders Cardiac failure congestive	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Cardiac disorders Myocardial infarction	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.0% 1/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
General disorders Generalized edema	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Hepatobiliary disorders Hepatotoxicity	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Infections and infestations Cellulitis	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.0% 1/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Infections and infestations Pneumonia	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Psychiatric disorders Confusional state	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.

Other adverse events

Other adverse events
Measure	ZS 10 g TID (Acute Phase) n=258 participants at risk ZS (sodium zirconium cyclosilicate) 10 g, three times a day, orally as suspension in water for 48 hours.	Placebo Comparator (Maintenance Phase) n=85 participants at risk Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.	ZS 5 g Once Daily (Maintenance Phase) n=45 participants at risk Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 10 g Once Daily (Maintenance Phase) n=51 participants at risk Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.	ZS 15 g Once Daily (Maintenance Phase) n=56 participants at risk Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Infections and infestations Upper respiratory infection	0.39% 1/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	6.7% 3/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.0% 1/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Gastrointestinal disorders Diarrhoea	1.2% 3/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	3.6% 2/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Cardiac disorders Cardiac failure congestive	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Gastrointestinal disorders Abdominal pain	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Gastrointestinal disorders Dyspepsia	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	4.4% 2/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Gastrointestinal disorders Nausea	0.78% 2/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Blood and lymphatic system disorders Anemia	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	5.4% 3/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Gastrointestinal disorders Constipation	0.78% 2/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	7.1% 6/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.0% 1/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
General disorders Edema	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.4% 2/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	5.9% 3/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	14.3% 8/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
General disorders Fatigue	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	9.8% 5/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	10.7% 6/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Infections and infestations Nasopharyngitis	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	5.4% 3/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Gastrointestinal disorders Vomiting	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Vascular disorders Hypertension	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	4.4% 2/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.0% 1/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	3.6% 2/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Respiratory, thoracic and mediastinal disorders Dysponea	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
General disorders Generalised Oedema	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	3.6% 2/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
General disorders Oedema peripheral	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.4% 2/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	5.9% 3/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	10.7% 6/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Infections and infestations Influenza	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.0% 1/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	3.6% 2/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Infections and infestations Pneumonia	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Infections and infestations Urinary tract infection bacterial	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Investigations Electrocardiogram QT prolonged	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Metabolism and nutrition disorders Gout	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.0% 1/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.4% 2/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.0% 1/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Nervous system disorders Dizziness	0.78% 2/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.0% 1/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Renal and urinary disorders Dysuria	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	2.2% 1/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Renal and urinary disorders Haematuria	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.2% 1/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	1.8% 1/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Renal and urinary disorders Renal failure	0.00% 0/258 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/85 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	4.4% 2/45 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/51 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.	0.00% 0/56 • All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.

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