Trial Outcomes & Findings for A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia (NCT NCT02875834)
NCT ID: NCT02875834
Last Updated: 2020-08-19
Results Overview
Comparison between placebo and the active ZS treatment groups (each dose group will be sequentially compared with placebo, starting with the highest and ending with the lowest dose) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29. The results in the table below are presented for RTP.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
267 participants
Primary outcome timeframe
Through 28-day randomized treatment study phase day 8-29.
Results posted on
2020-08-19
Participant Flow
This study was conducted in 42 centers within Japan, Russia, South Korea, and Taiwan.
the study consisted of two phases: an open-label phase (single arm, 48 hours, ZS 10 g TID; OLP) and a randomized treatment phase (3 arms, 28 days; RTP). 267 patients entered OLP. Out of these, 248 endered RTP and were randomized to placebo, ZS 5 g QD or ZS 10 g QD in a 1:2:2 ratio.
Participant milestones
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Open-label Phase
STARTED
|
267
|
0
|
0
|
0
|
|
Open-label Phase
COMPLETED
|
260
|
0
|
0
|
0
|
|
Open-label Phase
NOT COMPLETED
|
7
|
0
|
0
|
0
|
|
Randomized Treatment Phase
STARTED
|
0
|
99
|
99
|
50
|
|
Randomized Treatment Phase
COMPLETED
|
0
|
85
|
88
|
41
|
|
Randomized Treatment Phase
NOT COMPLETED
|
0
|
14
|
11
|
9
|
Reasons for withdrawal
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Open-label Phase
Withdrawal by Subject
|
3
|
0
|
0
|
0
|
|
Open-label Phase
(Not collected)
|
4
|
0
|
0
|
0
|
|
Randomized Treatment Phase
Withdrawal by Subject
|
0
|
3
|
1
|
0
|
|
Randomized Treatment Phase
Protocol Violation
|
0
|
2
|
0
|
0
|
|
Randomized Treatment Phase
(Not collected)
|
0
|
9
|
10
|
9
|
Baseline Characteristics
RTP: For the 28-day randomized treatment study phase, the Full Analysis Set (FAS) will include all patients who are randomized to the 28-day randomized treatment study phase.
Baseline characteristics by cohort
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
n=267 Participants
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
Total
n=515 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
67.8 Years
STANDARD_DEVIATION 10.80 • n=5 Participants • RTP: For the 28-day randomized treatment study phase, the Full Analysis Set (FAS) will include all patients who are randomized to the 28-day randomized treatment study phase.
|
66.7 Years
STANDARD_DEVIATION 11.40 • n=7 Participants • RTP: For the 28-day randomized treatment study phase, the Full Analysis Set (FAS) will include all patients who are randomized to the 28-day randomized treatment study phase.
|
68.0 Years
STANDARD_DEVIATION 10.18 • n=5 Participants • RTP: For the 28-day randomized treatment study phase, the Full Analysis Set (FAS) will include all patients who are randomized to the 28-day randomized treatment study phase.
|
69.4 Years
STANDARD_DEVIATION 10.26 • n=4 Participants • RTP: For the 28-day randomized treatment study phase, the Full Analysis Set (FAS) will include all patients who are randomized to the 28-day randomized treatment study phase.
|
67.7 Years
STANDARD_DEVIATION 10.70 • n=21 Participants • RTP: For the 28-day randomized treatment study phase, the Full Analysis Set (FAS) will include all patients who are randomized to the 28-day randomized treatment study phase.
|
|
Sex: Female, Male
Female
|
96 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
184 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
171 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
36 Participants
n=4 Participants
|
331 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
265 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
98 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
511 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
227 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
43 Participants
n=4 Participants
|
443 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
40 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
72 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Country
Japan
|
68 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
134 Participants
n=21 Participants
|
|
Country
Korea
|
121 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
235 Participants
n=21 Participants
|
|
Country
Russia
|
40 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
72 Participants
n=21 Participants
|
|
Country
Taiwan
|
38 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
74 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Through 28-day randomized treatment study phase day 8-29.Population: Full Analysis Set
Comparison between placebo and the active ZS treatment groups (each dose group will be sequentially compared with placebo, starting with the highest and ending with the lowest dose) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29. The results in the table below are presented for RTP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Least Square Mean S-K Level on Days 8-29
|
—
|
4.811 mmol/L
Interval 4.685 to 4.94
|
4.381 mmol/L
Interval 4.265 to 4.501
|
5.321 mmol/L
Interval 5.155 to 5.493
|
SECONDARY outcome
Timeframe: Through 48-hour initial phase.Population: Full Analysis Set
Proportion of patients who achieve normokalemia during the initial phase at 24 and 48 hours. The results in the table below are presented for OLP. (h=hours).
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
n=267 Participants
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Proportion of Patients Achieving Normokalemia
Normokalemic at 24h
|
169 Participants
|
—
|
—
|
—
|
|
Proportion of Patients Achieving Normokalemia
Not Normokalemic at 24h
|
93 Participants
|
—
|
—
|
—
|
|
Proportion of Patients Achieving Normokalemia
Missing at 24h
|
5 Participants
|
—
|
—
|
—
|
|
Proportion of Patients Achieving Normokalemia
Normokalemic at 48h
|
238 Participants
|
—
|
—
|
—
|
|
Proportion of Patients Achieving Normokalemia
Not Normokalemic at 48h
|
22 Participants
|
—
|
—
|
—
|
|
Proportion of Patients Achieving Normokalemia
Missing at 48h
|
7 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Through 48-hour initial phase.Population: Full Analysis Set
Exponential rate of change in S-K levels (blood) during the 48-hour open-label initial phase. The results in the table below are presented for OLP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
n=267 Participants
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Exponential Rate of Change in S-K Levels
|
-0.004 log(mmol/L)/h
Standard Error 0.0001
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Through 48-hour initial phase.Population: Full Analysis Set
Absolute change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
n=267 Participants
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Absolute Change From Baseline in S-K Levels
OLP Day 1-1h post-first dose absolute change
|
-0.19 mmol/L
Standard Deviation 0.444
|
—
|
—
|
—
|
|
Absolute Change From Baseline in S-K Levels
OLP Day 1-2h post-first dose absolute change
|
-0.48 mmol/L
Standard Deviation 0.452
|
—
|
—
|
—
|
|
Absolute Change From Baseline in S-K Levels
OLP Day 1-4h post-first dose absolute change
|
-0.57 mmol/L
Standard Deviation 0.494
|
—
|
—
|
—
|
|
Absolute Change From Baseline in S-K Levels
OLP Day 2-24h absolute change
|
-0.81 mmol/L
Standard Deviation 0.398
|
—
|
—
|
—
|
|
Absolute Change From Baseline in S-K Levels
OLP Day 2-1h post-first dose absolute change
|
-0.91 mmol/L
Standard Deviation 0.445
|
—
|
—
|
—
|
|
Absolute Change From Baseline in S-K Levels
OLP Day 3-48h absolute change
|
-1.28 mmol/L
Standard Deviation 0.499
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Through 48-hour initial phase.Population: Full Analysis Set
Percentage change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
n=267 Participants
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Percentage Change From Baseline in S-K Levels
OLP Day 1-4h post-first dose percentage change
|
-9.88 Percentage change
Standard Deviation 8.494
|
—
|
—
|
—
|
|
Percentage Change From Baseline in S-K Levels
OLP Day 2-24h percentage change
|
-14.08 Percentage change
Standard Deviation 6.479
|
—
|
—
|
—
|
|
Percentage Change From Baseline in S-K Levels
OLP Day 2-1h post-first dose percentage change
|
-15.84 Percentage change
Standard Deviation 7.243
|
—
|
—
|
—
|
|
Percentage Change From Baseline in S-K Levels
OLP Day 1-1h post-first dose percentage change
|
-3.26 Percentage change
Standard Deviation 7.949
|
—
|
—
|
—
|
|
Percentage Change From Baseline in S-K Levels
OLP Day 1-2h post-first dose percentage change
|
-8.29 Percentage change
Standard Deviation 7.792
|
—
|
—
|
—
|
|
Percentage Change From Baseline in S-K Levels
OLP Day 3-48h percentage change
|
-22.16 Percentage change
Standard Deviation 7.812
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Through 28-day randomized treatment study phase day 8-29.Population: Full Analysis Set
The proportion of patients who remain normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) at the end of the 28-day randomized treatment study phase and during the 28-day randomized treatment study phase. The results in the table below are presented for RTP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Proportion of Patients Remaining Normokalemic
|
—
|
58 Participants
|
75 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Through 28-day randomized treatment phase.Population: Full Analysis Set
The proportion of patients who are normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) at Day 1 through Day 29/Exit in randomization phase. The results in the table below are presented for RTP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 5
|
—
|
71 Participants
|
89 Participants
|
27 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 1
|
—
|
93 Participants
|
94 Participants
|
45 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 2
|
—
|
89 Participants
|
93 Participants
|
40 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 8
|
—
|
62 Participants
|
81 Participants
|
16 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 12
|
—
|
62 Participants
|
78 Participants
|
12 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 15
|
—
|
57 Participants
|
77 Participants
|
12 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 19
|
—
|
55 Participants
|
76 Participants
|
11 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 22
|
—
|
54 Participants
|
73 Participants
|
11 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 26
|
—
|
56 Participants
|
74 Participants
|
8 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 29
|
—
|
51 Participants
|
71 Participants
|
11 Participants
|
|
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
Day 29/Exit
|
—
|
58 Participants
|
77 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Through 28-day randomized treatment phase.Population: Full Analysis Set
The number of days patients remain normokalemic during the 28-day randomized treatment study phase. The results in the table below are presented for RTP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Days Patients Remain Normokalemic
|
—
|
10.810 Day
Standard Error 1.113
|
15.623 Day
Standard Error 1.143
|
3.543 Day
Standard Error 1.351
|
SECONDARY outcome
Timeframe: Through 28-day randomized treatment phase.Population: Full Analysis Set
The mean change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Mean Change in S-K Levels
Day 2 change from RTP baseline
|
—
|
0.03 mmol/L
Standard Deviation 0.354
|
-0.09 mmol/L
Standard Deviation 0.372
|
0.17 mmol/L
Standard Deviation 0.443
|
|
Mean Change in S-K Levels
Day 5 change from RTP baseline
|
—
|
0.23 mmol/L
Standard Deviation 0.478
|
-0.08 mmol/L
Standard Deviation 0.439
|
0.60 mmol/L
Standard Deviation 0.562
|
|
Mean Change in S-K Levels
Day 12 change from RTP baseline
|
—
|
0.53 mmol/L
Standard Deviation 0.560
|
0.05 mmol/L
Standard Deviation 0.573
|
0.97 mmol/L
Standard Deviation 0.646
|
|
Mean Change in S-K Levels
Day 15 change from RTP baseline
|
—
|
0.54 mmol/L
Standard Deviation 0.584
|
0.04 mmol/L
Standard Deviation 0.564
|
0.85 mmol/L
Standard Deviation 0.585
|
|
Mean Change in S-K Levels
EOS change from RTP baseline
|
—
|
0.92 mmol/L
Standard Deviation 0.661
|
0.77 mmol/L
Standard Deviation 0.695
|
0.88 mmol/L
Standard Deviation 0.684
|
|
Mean Change in S-K Levels
Day 2 change from OLP baseline
|
—
|
-1.28 mmol/L
Standard Deviation 0.544
|
-1.36 mmol/L
Standard Deviation 0.515
|
-1.07 mmol/L
Standard Deviation 0.602
|
|
Mean Change in S-K Levels
Day 5 change from OLP baseline
|
—
|
-1.08 mmol/L
Standard Deviation 0.552
|
-1.35 mmol/L
Standard Deviation 0.601
|
-0.64 mmol/L
Standard Deviation 0.594
|
|
Mean Change in S-K Levels
Day 12 change from OLP baseline
|
—
|
-0.79 mmol/L
Standard Deviation 0.603
|
-1.21 mmol/L
Standard Deviation 0.671
|
-0.28 mmol/L
Standard Deviation 0.602
|
|
Mean Change in S-K Levels
Day 8 change from RTP baseline
|
—
|
0.44 mmol/L
Standard Deviation 0.487
|
0.00 mmol/L
Standard Deviation 0.489
|
0.91 mmol/L
Standard Deviation 0.622
|
|
Mean Change in S-K Levels
Day 19 change from RTP baseline
|
—
|
0.56 mmol/L
Standard Deviation 0.578
|
0.05 mmol/L
Standard Deviation 0.576
|
0.97 mmol/L
Standard Deviation 0.566
|
|
Mean Change in S-K Levels
Day 22 change from RTP baseline
|
—
|
0.47 mmol/L
Standard Deviation 0.555
|
0.10 mmol/L
Standard Deviation 0.613
|
0.93 mmol/L
Standard Deviation 0.702
|
|
Mean Change in S-K Levels
Day 26 change from RTP baseline
|
—
|
0.51 mmol/L
Standard Deviation 0.581
|
0.05 mmol/L
Standard Deviation 0.639
|
1.01 mmol/L
Standard Deviation 0.607
|
|
Mean Change in S-K Levels
Day 29 change from RTP baseline
|
—
|
0.47 mmol/L
Standard Deviation 0.586
|
0.02 mmol/L
Standard Deviation 0.665
|
1.02 mmol/L
Standard Deviation 0.594
|
|
Mean Change in S-K Levels
Day 8 change from OLP baseline
|
—
|
-0.87 mmol/L
Standard Deviation 0.578
|
-1.28 mmol/L
Standard Deviation 0.634
|
-0.34 mmol/L
Standard Deviation 0.661
|
|
Mean Change in S-K Levels
Day 15 change from OLP baseline
|
—
|
-0.77 mmol/L
Standard Deviation 0.604
|
-1.23 mmol/L
Standard Deviation 0.643
|
-0.40 mmol/L
Standard Deviation 0.550
|
|
Mean Change in S-K Levels
Day 19 change from OLP baseline
|
—
|
-0.74 mmol/L
Standard Deviation 0.639
|
-1.20 mmol/L
Standard Deviation 0.672
|
-0.30 mmol/L
Standard Deviation 0.533
|
|
Mean Change in S-K Levels
Day 22 change from OLP baseline
|
—
|
-0.84 mmol/L
Standard Deviation 0.597
|
-1.15 mmol/L
Standard Deviation 0.730
|
-0.38 mmol/L
Standard Deviation 0.571
|
|
Mean Change in S-K Levels
Day 26 change from OLP baseline
|
—
|
-0.79 mmol/L
Standard Deviation 0.687
|
-1.21 mmol/L
Standard Deviation 0.762
|
-0.28 mmol/L
Standard Deviation 0.563
|
|
Mean Change in S-K Levels
Day 29 change from OLP baseline
|
—
|
-0.82 mmol/L
Standard Deviation 0.604
|
-1.24 mmol/L
Standard Deviation 0.734
|
-0.27 mmol/L
Standard Deviation 0.515
|
|
Mean Change in S-K Levels
EOS change from OLP baseline
|
—
|
-0.39 mmol/L
Standard Deviation 0.649
|
-0.50 mmol/L
Standard Deviation 0.725
|
-0.36 mmol/L
Standard Deviation 0.702
|
SECONDARY outcome
Timeframe: Through 28-day randomized treatment phase.Population: Full Analysis Set
The mean percentage change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Mean Percentage Change in S-K Levels
Day 5 percentage change from RTP baseline
|
—
|
5.51 Percentage change
Standard Deviation 11.337
|
-1.52 Percentage change
Standard Deviation 9.691
|
14.19 Percentage change
Standard Deviation 13.162
|
|
Mean Percentage Change in S-K Levels
Day 8 percentage change from RTP baseline
|
—
|
10.26 Percentage change
Standard Deviation 11.340
|
0.16 Percentage change
Standard Deviation 11.062
|
21.55 Percentage change
Standard Deviation 15.634
|
|
Mean Percentage Change in S-K Levels
Day 22 percentage change from RTP baseline
|
—
|
11.04 Percentage change
Standard Deviation 12.993
|
2.66 Percentage change
Standard Deviation 14.042
|
22.28 Percentage change
Standard Deviation 18.131
|
|
Mean Percentage Change in S-K Levels
Day 2 percentage change from OLP baseline
|
—
|
-22.12 Percentage change
Standard Deviation 8.679
|
-23.55 Percentage change
Standard Deviation 7.652
|
-18.51 Percentage change
Standard Deviation 9.751
|
|
Mean Percentage Change in S-K Levels
Day 5 percentage change from OLP baseline
|
—
|
-18.77 Percentage change
Standard Deviation 9.347
|
-23.31 Percentage change
Standard Deviation 9.230
|
-10.96 Percentage change
Standard Deviation 9.724
|
|
Mean Percentage Change in S-K Levels
Day 29 percentage change from OLP baseline
|
—
|
-14.09 Percentage change
Standard Deviation 9.949
|
-21.42 Percentage change
Standard Deviation 11.659
|
-4.61 Percentage change
Standard Deviation 8.802
|
|
Mean Percentage Change in S-K Levels
Day 2 percentage change from RTP baseline
|
—
|
1.00 Percentage change
Standard Deviation 8.459
|
-1.74 Percentage change
Standard Deviation 7.981
|
4.19 Percentage change
Standard Deviation 10.592
|
|
Mean Percentage Change in S-K Levels
Day 12 percentage change from RTP baseline
|
—
|
12.41 Percentage change
Standard Deviation 13.113
|
1.60 Percentage change
Standard Deviation 13.205
|
22.87 Percentage change
Standard Deviation 16.457
|
|
Mean Percentage Change in S-K Levels
Day 15 percentage change from RTP baseline
|
—
|
12.50 Percentage change
Standard Deviation 13.378
|
1.27 Percentage change
Standard Deviation 12.937
|
20.15 Percentage change
Standard Deviation 14.647
|
|
Mean Percentage Change in S-K Levels
Day 19 percentage change from RTP baseline
|
—
|
13.12 Percentage change
Standard Deviation 13.180
|
1.70 Percentage change
Standard Deviation 13.139
|
22.77 Percentage change
Standard Deviation 14.583
|
|
Mean Percentage Change in S-K Levels
Day 26 percentage change from RTP baseline
|
—
|
12.02 Percentage change
Standard Deviation 13.616
|
1.49 Percentage change
Standard Deviation 14.441
|
23.63 Percentage change
Standard Deviation 15.353
|
|
Mean Percentage Change in S-K Levels
Day 29 percentage change from RTP baseline
|
—
|
11.34 Percentage change
Standard Deviation 13.821
|
0.87 Percentage change
Standard Deviation 15.084
|
23.99 Percentage change
Standard Deviation 15.329
|
|
Mean Percentage Change in S-K Levels
EOS percentage change from RTP baseline
|
—
|
21.62 Percentage change
Standard Deviation 16.027
|
17.76 Percentage change
Standard Deviation 16.266
|
20.70 Percentage change
Standard Deviation 17.035
|
|
Mean Percentage Change in S-K Levels
Day 8 percentage change from OLP baseline
|
—
|
-15.01 Percentage change
Standard Deviation 9.627
|
-22.01 Percentage change
Standard Deviation 10.037
|
-5.41 Percentage change
Standard Deviation 11.424
|
|
Mean Percentage Change in S-K Levels
Day 12 percentage change from OLP baseline
|
—
|
-13.55 Percentage change
Standard Deviation 9.891
|
-20.84 Percentage change
Standard Deviation 10.981
|
-4.57 Percentage change
Standard Deviation 10.335
|
|
Mean Percentage Change in S-K Levels
Day 15 percentage change from OLP baseline
|
—
|
-13.35 Percentage change
Standard Deviation 10.170
|
-21.18 Percentage change
Standard Deviation 10.351
|
-6.63 Percentage change
Standard Deviation 9.457
|
|
Mean Percentage Change in S-K Levels
Day 19 percentage change from OLP baseline
|
—
|
-12.79 Percentage change
Standard Deviation 11.339
|
-20.67 Percentage change
Standard Deviation 10.834
|
-4.89 Percentage change
Standard Deviation 9.279
|
|
Mean Percentage Change in S-K Levels
Day 22 percentage change from OLP baseline
|
—
|
-14.49 Percentage change
Standard Deviation 10.158
|
-19.67 Percentage change
Standard Deviation 11.723
|
-6.43 Percentage change
Standard Deviation 9.759
|
|
Mean Percentage Change in S-K Levels
Day 26 percentage change from OLP baseline
|
—
|
-13.35 Percentage change
Standard Deviation 11.599
|
-20.75 Percentage change
Standard Deviation 12.360
|
-4.74 Percentage change
Standard Deviation 9.551
|
|
Mean Percentage Change in S-K Levels
EOS percentage change from OLP baseline
|
—
|
-6.57 Percentage change
Standard Deviation 11.199
|
-8.54 Percentage change
Standard Deviation 12.405
|
-5.95 Percentage change
Standard Deviation 11.927
|
SECONDARY outcome
Timeframe: Through 28-day randomized treatment phase.Population: Full Analysis Set
The results represent number of hyperkalemic patients during the 28-day randomized treatment study phase. The results in the table below are presented for RTP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Number of Hyperkalemic Patients
|
—
|
66 Participants
|
45 Participants
|
47 Participants
|
SECONDARY outcome
Timeframe: Through 28-day randomized treatment phase.Population: Full Analysis Set
The mean changes from OLP baseline in S-Aldosterone and P-Renin levels. The results in the table below are presented for RTP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Mean Changes in S-Aldosterone and P Renin Levels
Day 1 S-Aldosterone
|
—
|
-112.69 pmol/L
Standard Deviation 178.358
|
-85.63 pmol/L
Standard Deviation 118.017
|
-98.54 pmol/L
Standard Deviation 168.657
|
|
Mean Changes in S-Aldosterone and P Renin Levels
Day 29 S-Aldosterone
|
—
|
-102.70 pmol/L
Standard Deviation 212.187
|
-90.22 pmol/L
Standard Deviation 91.149
|
41.07 pmol/L
Standard Deviation 198.266
|
|
Mean Changes in S-Aldosterone and P Renin Levels
Day 1 P-Renin
|
—
|
-0.23 pmol/L
Standard Deviation 1.158
|
-0.26 pmol/L
Standard Deviation 1.913
|
-0.30 pmol/L
Standard Deviation 1.031
|
|
Mean Changes in S-Aldosterone and P Renin Levels
Day 15 P-Renin
|
—
|
-0.39 pmol/L
Standard Deviation 1.350
|
-1.09 pmol/L
Standard Deviation 4.732
|
0.60 pmol/L
Standard Deviation 3.250
|
|
Mean Changes in S-Aldosterone and P Renin Levels
Day 29 P-Renin
|
—
|
-0.27 pmol/L
Standard Deviation 1.008
|
-1.56 pmol/L
Standard Deviation 4.165
|
-0.25 pmol/L
Standard Deviation 2.725
|
|
Mean Changes in S-Aldosterone and P Renin Levels
Day 15 S-Aldosterone
|
—
|
-91.75 pmol/L
Standard Deviation 179.791
|
-96.37 pmol/L
Standard Deviation 108.002
|
39.78 pmol/L
Standard Deviation 152.050
|
SECONDARY outcome
Timeframe: Through study completion, an average of 37 days.Population: Full Analysis Set
Evaluate health state of patients using EQ-5D questionnaire. This scale is numbered from 0 to 100. 0 means the worst health you can imagine. 100 means the best health you can imagine. The results in the table below are presented for RTP.
Outcome measures
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 Participants
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 Participants
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 Participants
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Patient Reported Health State (EQ-5D) Questionnaire
OLP baseline
|
—
|
75.0 Units on a scale
Standard Deviation 16.44
|
74.3 Units on a scale
Standard Deviation 17.44
|
72.7 Units on a scale
Standard Deviation 17.32
|
|
Patient Reported Health State (EQ-5D) Questionnaire
Day 29
|
—
|
77.6 Units on a scale
Standard Deviation 16.50
|
76.9 Units on a scale
Standard Deviation 16.08
|
76.6 Units on a scale
Standard Deviation 14.08
|
Adverse Events
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Sodium Zirconium Cyclosilicate (ZS) 5g
Serious events: 4 serious events
Other events: 6 other events
Deaths: 0 deaths
Sodium Zirconium Cyclosilicate (ZS) 10g
Serious events: 3 serious events
Other events: 21 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
n=267 participants at risk
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 participants at risk
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 participants at risk
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 participants at risk
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
Infections and infestations
Cystitis
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Infections and infestations
Infectious colitis
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Infections and infestations
Pneumonia
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Vascular disorders
Hypertension
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/99 • Through 28-day randomized treatment study phase day 8-29
|
2.0%
1/50 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
Other adverse events
| Measure |
Sodium Zirconium Cyclosilicate (ZS) 10g Tid
n=267 participants at risk
Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 5g
n=99 participants at risk
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Sodium Zirconium Cyclosilicate (ZS) 10g
n=99 participants at risk
Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase.
|
Placebo
n=50 participants at risk
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
|
|---|---|---|---|---|
|
General disorders
Oedema peripheral
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
4.0%
4/99 • Number of events 4 • Through 28-day randomized treatment study phase day 8-29
|
7.1%
7/99 • Number of events 7 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
9.1%
9/99 • Number of events 9 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
|
General disorders
Oedema
|
0.00%
0/267 • Through 28-day randomized treatment study phase day 8-29
|
1.0%
1/99 • Number of events 1 • Through 28-day randomized treatment study phase day 8-29
|
8.1%
8/99 • Number of events 9 • Through 28-day randomized treatment study phase day 8-29
|
0.00%
0/50 • Through 28-day randomized treatment study phase day 8-29
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place