Hyperkalemia
Conditions
Brief summary
To evaluate the efficacy of two different doses (5 and 10 g) of ZS orally administered once daily (qd) vs placebo in maintaining normokalemia in initially hyperkalemic patients having achieved normokalemia following two days of initial ZS therapy (10g TID).
Interventions
Suspension administered 10g orally three times per day, in the first 48-hour of the study for all patients (48-hour open label initial phase)
Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase.
DRUGPlacebo
Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent prior to any study specific procedures * Female and male patients aged ≥18 and ≤ 90 years * Two consecutive i-STAT potassium values, measured 60-minutes (± 10 minutes) apart, both ≥ 5.1 mmol/l and measured within 1 day of the first ZS dose on 48-hour open-label initial phase Day 1 * Ability to have repeated blood draws or effective venous catheterization * Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy.
Exclusion criteria
* Involvement in the planning and/or conduct of the study * Participation in another clinical study with an investigational product during the last 3 months * Pseudohyperkalemia signs and symptoms * Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug * Patients treated with resins,calcium acetate,calcium carbonate, or lanthanum carbonate,within 7 days prior to the first dose of study drug * Patients with a life expectancy of less than 3 months * Patients who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the subjects' tasks associated with the protocol * Female patients who are pregnant, lactating, or planning to become pregnant * Patients with diabetic ketoacidosis * Presence of any condition which, in the opinion of the investigator, places the patient at undue risk or potentially jeopardizes the quality of the data to be generated * Known hypersensitivity or previous anaphylaxis to ZS or to components thereof * Patients with cardiac arrhythmias that require immediate treatment * Patients on dialysis * Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of ZS
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Square Mean S-K Level on Days 8-29 | Through 28-day randomized treatment study phase day 8-29. | Comparison between placebo and the active ZS treatment groups (each dose group will be sequentially compared with placebo, starting with the highest and ending with the lowest dose) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29. The results in the table below are presented for RTP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exponential Rate of Change in S-K Levels | Through 48-hour initial phase. | Exponential rate of change in S-K levels (blood) during the 48-hour open-label initial phase. The results in the table below are presented for OLP. |
| Absolute Change From Baseline in S-K Levels | Through 48-hour initial phase. | Absolute change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP. |
| Percentage Change From Baseline in S-K Levels | Through 48-hour initial phase. | Percentage change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP. |
| Proportion of Patients Remaining Normokalemic | Through 28-day randomized treatment study phase day 8-29. | The proportion of patients who remain normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) at the end of the 28-day randomized treatment study phase and during the 28-day randomized treatment study phase. The results in the table below are presented for RTP. |
| Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Through 28-day randomized treatment phase. | The proportion of patients who are normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) at Day 1 through Day 29/Exit in randomization phase. The results in the table below are presented for RTP. |
| Proportion of Patients Achieving Normokalemia | Through 48-hour initial phase. | Proportion of patients who achieve normokalemia during the initial phase at 24 and 48 hours. The results in the table below are presented for OLP. (h=hours). |
| Mean Change in S-K Levels | Through 28-day randomized treatment phase. | The mean change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP. |
| Mean Percentage Change in S-K Levels | Through 28-day randomized treatment phase. | The mean percentage change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP. |
| Number of Hyperkalemic Patients | Through 28-day randomized treatment phase. | The results represent number of hyperkalemic patients during the 28-day randomized treatment study phase. The results in the table below are presented for RTP. |
| Mean Changes in S-Aldosterone and P Renin Levels | Through 28-day randomized treatment phase. | The mean changes from OLP baseline in S-Aldosterone and P-Renin levels. The results in the table below are presented for RTP. |
| Patient Reported Health State (EQ-5D) Questionnaire | Through study completion, an average of 37 days. | Evaluate health state of patients using EQ-5D questionnaire. This scale is numbered from 0 to 100. 0 means the worst health you can imagine. 100 means the best health you can imagine. The results in the table below are presented for RTP. |
| Days Patients Remain Normokalemic | Through 28-day randomized treatment phase. | The number of days patients remain normokalemic during the 28-day randomized treatment study phase. The results in the table below are presented for RTP. |
Countries
Japan, Russia, South Korea, Taiwan
Participant flow
Recruitment details
This study was conducted in 42 centers within Japan, Russia, South Korea, and Taiwan.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid Suspension administered 10g orally 3 times per day for the first 48-hour open label initial phase. | 267 |
| Sodium Zirconium Cyclosilicate (ZS) 5g Suspension administered 5g orally once daily for 28 days after the first 48-hour open label initial phase. | 99 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Suspension administered 10g orally once daily for 28 days after the first 48-hour open label initial phase. | 99 |
| Placebo Suspension administered orally placebo once daily for 28 days after the first 48-hour open label initial phase. | 50 |
| Total | 515 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Open-label Phase | (Not collected) | 4 | 0 | 0 | 0 |
| Open-label Phase | Withdrawal by Subject | 3 | 0 | 0 | 0 |
| Randomized Treatment Phase | (Not collected) | 0 | 9 | 10 | 9 |
| Randomized Treatment Phase | Protocol Violation | 0 | 2 | 0 | 0 |
| Randomized Treatment Phase | Withdrawal by Subject | 0 | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Total | Placebo | Sodium Zirconium Cyclosilicate (ZS) 10g | Sodium Zirconium Cyclosilicate (ZS) 5g |
|---|---|---|---|---|---|
| Age, Continuous | 67.8 Years STANDARD_DEVIATION 10.8 | 67.7 Years STANDARD_DEVIATION 10.7 | 69.4 Years STANDARD_DEVIATION 10.26 | 68.0 Years STANDARD_DEVIATION 10.18 | 66.7 Years STANDARD_DEVIATION 11.4 |
| Country Japan | 68 Participants | 134 Participants | 13 Participants | 27 Participants | 26 Participants |
| Country Korea | 121 Participants | 235 Participants | 23 Participants | 45 Participants | 46 Participants |
| Country Russia | 40 Participants | 72 Participants | 7 Participants | 13 Participants | 12 Participants |
| Country Taiwan | 38 Participants | 74 Participants | 7 Participants | 14 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 265 Participants | 511 Participants | 49 Participants | 98 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 227 Participants | 443 Participants | 43 Participants | 86 Participants | 87 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 72 Participants | 7 Participants | 13 Participants | 12 Participants |
| Sex: Female, Male Female | 96 Participants | 184 Participants | 14 Participants | 38 Participants | 36 Participants |
| Sex: Female, Male Male | 171 Participants | 331 Participants | 36 Participants | 61 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 267 | 0 / 99 | 0 / 99 | 0 / 50 |
| other Total, other adverse events | 0 / 267 | 6 / 99 | 21 / 99 | 0 / 50 |
| serious Total, serious adverse events | 0 / 267 | 4 / 99 | 3 / 99 | 1 / 50 |
Outcome results
Primary
Least Square Mean S-K Level on Days 8-29
Comparison between placebo and the active ZS treatment groups (each dose group will be sequentially compared with placebo, starting with the highest and ending with the lowest dose) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29. The results in the table below are presented for RTP.
Time frame: Through 28-day randomized treatment study phase day 8-29.
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 5g | Least Square Mean S-K Level on Days 8-29 | 4.811 mmol/L |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Least Square Mean S-K Level on Days 8-29 | 4.381 mmol/L |
| Placebo | Least Square Mean S-K Level on Days 8-29 | 5.321 mmol/L |
Comparison: Results derived from a mixed effects model of log-transformed S-K levels. Fixed effects are: treatment group; visit; treatment-by-visit interaction; baseline S-K values (OLP and RTP); baseline eGFR; age category; country; baseline RAAS inhibitor, chronic kidney disease, heart failure, and diabetes mellitus statuses. Patient is a random effect. p-values given are for differences of LSMEANS. The back-transformation is to the original scale of the S-K measurement.p-value: <0.00195% CI: [0.876, 0.933]Mixed Models Analysis
p-value: <0.00195% CI: [0.797, 0.85]Mixed Models Analysis
Secondary
Absolute Change From Baseline in S-K Levels
Absolute change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.
Time frame: Through 48-hour initial phase.
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | 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 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | 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 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | 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 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Absolute Change From Baseline in S-K Levels | OLP Day 2-24h absolute change | -0.81 mmol/L | Standard Deviation 0.398 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | 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 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Absolute Change From Baseline in S-K Levels | OLP Day 3-48h absolute change | -1.28 mmol/L | Standard Deviation 0.499 |
Secondary
Days Patients Remain Normokalemic
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.
Time frame: Through 28-day randomized treatment phase.
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 5g | Days Patients Remain Normokalemic | 10.810 Day | Standard Error 1.113 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Days Patients Remain Normokalemic | 15.623 Day | Standard Error 1.143 |
| Placebo | Days Patients Remain Normokalemic | 3.543 Day | Standard Error 1.351 |
Comparison: Results derived from a linear regression model with the following covariates: treatment group; baseline S-K values (Open-label phase and Randomized treatment phase); baseline eGFR; age category; country; baseline RAAS inhibitor, chronic kidney disease, heart failure, and diabetes mellitus statuses.p-value: <0.00195% CI: [4.318, 10.214]Regression, Linear
p-value: <0.00195% CI: [9.118, 15.04]Regression, Linear
Secondary
Exponential Rate of Change in S-K Levels
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.
Time frame: Through 48-hour initial phase.
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Exponential Rate of Change in S-K Levels | -0.004 log(mmol/L)/h | Standard Error 0.0001 |
Secondary
Mean Change in S-K Levels
The mean change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.
Time frame: Through 28-day randomized treatment phase.
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 2 change from RTP baseline | 0.03 mmol/L | Standard Deviation 0.354 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 15 change from OLP baseline | -0.77 mmol/L | Standard Deviation 0.604 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 19 change from RTP baseline | 0.56 mmol/L | Standard Deviation 0.578 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 8 change from OLP baseline | -0.87 mmol/L | Standard Deviation 0.578 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 2 change from OLP baseline | -1.28 mmol/L | Standard Deviation 0.544 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 22 change from RTP baseline | 0.47 mmol/L | Standard Deviation 0.555 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 5 change from OLP baseline | -1.08 mmol/L | Standard Deviation 0.552 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | EOS change from RTP baseline | 0.92 mmol/L | Standard Deviation 0.661 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 26 change from RTP baseline | 0.51 mmol/L | Standard Deviation 0.581 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 5 change from RTP baseline | 0.23 mmol/L | Standard Deviation 0.478 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 29 change from RTP baseline | 0.47 mmol/L | Standard Deviation 0.586 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | EOS change from OLP baseline | -0.39 mmol/L | Standard Deviation 0.649 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 26 change from OLP baseline | -0.79 mmol/L | Standard Deviation 0.687 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 8 change from RTP baseline | 0.44 mmol/L | Standard Deviation 0.487 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 29 change from OLP baseline | -0.82 mmol/L | Standard Deviation 0.604 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 22 change from OLP baseline | -0.84 mmol/L | Standard Deviation 0.597 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 12 change from RTP baseline | 0.53 mmol/L | Standard Deviation 0.56 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 12 change from OLP baseline | -0.79 mmol/L | Standard Deviation 0.603 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 19 change from OLP baseline | -0.74 mmol/L | Standard Deviation 0.639 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Change in S-K Levels | Day 15 change from RTP baseline | 0.54 mmol/L | Standard Deviation 0.584 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 26 change from OLP baseline | -1.21 mmol/L | Standard Deviation 0.762 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 5 change from OLP baseline | -1.35 mmol/L | Standard Deviation 0.601 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 8 change from OLP baseline | -1.28 mmol/L | Standard Deviation 0.634 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 2 change from RTP baseline | -0.09 mmol/L | Standard Deviation 0.372 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 5 change from RTP baseline | -0.08 mmol/L | Standard Deviation 0.439 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 8 change from RTP baseline | 0.00 mmol/L | Standard Deviation 0.489 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 12 change from RTP baseline | 0.05 mmol/L | Standard Deviation 0.573 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 15 change from RTP baseline | 0.04 mmol/L | Standard Deviation 0.564 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 19 change from RTP baseline | 0.05 mmol/L | Standard Deviation 0.576 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 22 change from RTP baseline | 0.10 mmol/L | Standard Deviation 0.613 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 26 change from RTP baseline | 0.05 mmol/L | Standard Deviation 0.639 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 29 change from RTP baseline | 0.02 mmol/L | Standard Deviation 0.665 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | EOS change from RTP baseline | 0.77 mmol/L | Standard Deviation 0.695 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 2 change from OLP baseline | -1.36 mmol/L | Standard Deviation 0.515 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 12 change from OLP baseline | -1.21 mmol/L | Standard Deviation 0.671 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 15 change from OLP baseline | -1.23 mmol/L | Standard Deviation 0.643 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 19 change from OLP baseline | -1.20 mmol/L | Standard Deviation 0.672 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 22 change from OLP baseline | -1.15 mmol/L | Standard Deviation 0.73 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | Day 29 change from OLP baseline | -1.24 mmol/L | Standard Deviation 0.734 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Change in S-K Levels | EOS change from OLP baseline | -0.50 mmol/L | Standard Deviation 0.725 |
| Placebo | Mean Change in S-K Levels | Day 8 change from OLP baseline | -0.34 mmol/L | Standard Deviation 0.661 |
| Placebo | Mean Change in S-K Levels | Day 12 change from OLP baseline | -0.28 mmol/L | Standard Deviation 0.602 |
| Placebo | Mean Change in S-K Levels | Day 15 change from RTP baseline | 0.85 mmol/L | Standard Deviation 0.585 |
| Placebo | Mean Change in S-K Levels | EOS change from OLP baseline | -0.36 mmol/L | Standard Deviation 0.702 |
| Placebo | Mean Change in S-K Levels | Day 15 change from OLP baseline | -0.40 mmol/L | Standard Deviation 0.55 |
| Placebo | Mean Change in S-K Levels | Day 12 change from RTP baseline | 0.97 mmol/L | Standard Deviation 0.646 |
| Placebo | Mean Change in S-K Levels | Day 29 change from OLP baseline | -0.27 mmol/L | Standard Deviation 0.515 |
| Placebo | Mean Change in S-K Levels | Day 19 change from OLP baseline | -0.30 mmol/L | Standard Deviation 0.533 |
| Placebo | Mean Change in S-K Levels | Day 8 change from RTP baseline | 0.91 mmol/L | Standard Deviation 0.622 |
| Placebo | Mean Change in S-K Levels | Day 5 change from OLP baseline | -0.64 mmol/L | Standard Deviation 0.594 |
| Placebo | Mean Change in S-K Levels | Day 22 change from OLP baseline | -0.38 mmol/L | Standard Deviation 0.571 |
| Placebo | Mean Change in S-K Levels | Day 26 change from RTP baseline | 1.01 mmol/L | Standard Deviation 0.607 |
| Placebo | Mean Change in S-K Levels | Day 5 change from RTP baseline | 0.60 mmol/L | Standard Deviation 0.562 |
| Placebo | Mean Change in S-K Levels | Day 29 change from RTP baseline | 1.02 mmol/L | Standard Deviation 0.594 |
| Placebo | Mean Change in S-K Levels | Day 22 change from RTP baseline | 0.93 mmol/L | Standard Deviation 0.702 |
| Placebo | Mean Change in S-K Levels | Day 2 change from RTP baseline | 0.17 mmol/L | Standard Deviation 0.443 |
| Placebo | Mean Change in S-K Levels | EOS change from RTP baseline | 0.88 mmol/L | Standard Deviation 0.684 |
| Placebo | Mean Change in S-K Levels | Day 19 change from RTP baseline | 0.97 mmol/L | Standard Deviation 0.566 |
| Placebo | Mean Change in S-K Levels | Day 26 change from OLP baseline | -0.28 mmol/L | Standard Deviation 0.563 |
| Placebo | Mean Change in S-K Levels | Day 2 change from OLP baseline | -1.07 mmol/L | Standard Deviation 0.602 |
Secondary
Mean Changes in S-Aldosterone and P Renin Levels
The mean changes from OLP baseline in S-Aldosterone and P-Renin levels. The results in the table below are presented for RTP.
Time frame: Through 28-day randomized treatment phase.
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Changes in S-Aldosterone and P Renin Levels | Day 1 S-Aldosterone | -112.69 pmol/L | Standard Deviation 178.358 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Changes in S-Aldosterone and P Renin Levels | Day 15 S-Aldosterone | -91.75 pmol/L | Standard Deviation 179.791 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Changes in S-Aldosterone and P Renin Levels | Day 29 S-Aldosterone | -102.70 pmol/L | Standard Deviation 212.187 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Changes in S-Aldosterone and P Renin Levels | Day 1 P-Renin | -0.23 pmol/L | Standard Deviation 1.158 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Changes in S-Aldosterone and P Renin Levels | Day 15 P-Renin | -0.39 pmol/L | Standard Deviation 1.35 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Changes in S-Aldosterone and P Renin Levels | Day 29 P-Renin | -0.27 pmol/L | Standard Deviation 1.008 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Changes in S-Aldosterone and P Renin Levels | Day 29 P-Renin | -1.56 pmol/L | Standard Deviation 4.165 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Changes in S-Aldosterone and P Renin Levels | Day 1 S-Aldosterone | -85.63 pmol/L | Standard Deviation 118.017 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Changes in S-Aldosterone and P Renin Levels | Day 1 P-Renin | -0.26 pmol/L | Standard Deviation 1.913 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Changes in S-Aldosterone and P Renin Levels | Day 15 P-Renin | -1.09 pmol/L | Standard Deviation 4.732 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Changes in S-Aldosterone and P Renin Levels | Day 15 S-Aldosterone | -96.37 pmol/L | Standard Deviation 108.002 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Changes in S-Aldosterone and P Renin Levels | Day 29 S-Aldosterone | -90.22 pmol/L | Standard Deviation 91.149 |
| Placebo | Mean Changes in S-Aldosterone and P Renin Levels | Day 15 S-Aldosterone | 39.78 pmol/L | Standard Deviation 152.05 |
| Placebo | Mean Changes in S-Aldosterone and P Renin Levels | Day 29 S-Aldosterone | 41.07 pmol/L | Standard Deviation 198.266 |
| Placebo | Mean Changes in S-Aldosterone and P Renin Levels | Day 29 P-Renin | -0.25 pmol/L | Standard Deviation 2.725 |
| Placebo | Mean Changes in S-Aldosterone and P Renin Levels | Day 1 P-Renin | -0.30 pmol/L | Standard Deviation 1.031 |
| Placebo | Mean Changes in S-Aldosterone and P Renin Levels | Day 1 S-Aldosterone | -98.54 pmol/L | Standard Deviation 168.657 |
| Placebo | Mean Changes in S-Aldosterone and P Renin Levels | Day 15 P-Renin | 0.60 pmol/L | Standard Deviation 3.25 |
Secondary
Mean Percentage Change in S-K Levels
The mean percentage change in S-K levels evaluated relative to both baselines. The results in the table below are presented for RTP.
Time frame: Through 28-day randomized treatment phase.
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 15 percentage change from OLP baseline | -13.35 Percentage change | Standard Deviation 10.17 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 26 percentage change from RTP baseline | 12.02 Percentage change | Standard Deviation 13.616 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 29 percentage change from OLP baseline | -14.09 Percentage change | Standard Deviation 9.949 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 12 percentage change from OLP baseline | -13.55 Percentage change | Standard Deviation 9.891 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 29 percentage change from RTP baseline | 11.34 Percentage change | Standard Deviation 13.821 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 8 percentage change from RTP baseline | 10.26 Percentage change | Standard Deviation 11.34 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 8 percentage change from OLP baseline | -15.01 Percentage change | Standard Deviation 9.627 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | EOS percentage change from RTP baseline | 21.62 Percentage change | Standard Deviation 16.027 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 12 percentage change from RTP baseline | 12.41 Percentage change | Standard Deviation 13.113 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 5 percentage change from OLP baseline | -18.77 Percentage change | Standard Deviation 9.347 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 2 percentage change from OLP baseline | -22.12 Percentage change | Standard Deviation 8.679 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 26 percentage change from OLP baseline | -13.35 Percentage change | Standard Deviation 11.599 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 15 percentage change from RTP baseline | 12.50 Percentage change | Standard Deviation 13.378 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | EOS percentage change from OLP baseline | -6.57 Percentage change | Standard Deviation 11.199 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 22 percentage change from OLP baseline | -14.49 Percentage change | Standard Deviation 10.158 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 19 percentage change from RTP baseline | 13.12 Percentage change | Standard Deviation 13.18 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 5 percentage change from RTP baseline | 5.51 Percentage change | Standard Deviation 11.337 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 19 percentage change from OLP baseline | -12.79 Percentage change | Standard Deviation 11.339 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 22 percentage change from RTP baseline | 11.04 Percentage change | Standard Deviation 12.993 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Mean Percentage Change in S-K Levels | Day 2 percentage change from RTP baseline | 1.00 Percentage change | Standard Deviation 8.459 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 26 percentage change from OLP baseline | -20.75 Percentage change | Standard Deviation 12.36 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 12 percentage change from RTP baseline | 1.60 Percentage change | Standard Deviation 13.205 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 2 percentage change from RTP baseline | -1.74 Percentage change | Standard Deviation 7.981 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 5 percentage change from RTP baseline | -1.52 Percentage change | Standard Deviation 9.691 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 8 percentage change from RTP baseline | 0.16 Percentage change | Standard Deviation 11.062 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 15 percentage change from RTP baseline | 1.27 Percentage change | Standard Deviation 12.937 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 19 percentage change from RTP baseline | 1.70 Percentage change | Standard Deviation 13.139 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 22 percentage change from RTP baseline | 2.66 Percentage change | Standard Deviation 14.042 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 26 percentage change from RTP baseline | 1.49 Percentage change | Standard Deviation 14.441 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 29 percentage change from RTP baseline | 0.87 Percentage change | Standard Deviation 15.084 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | EOS percentage change from RTP baseline | 17.76 Percentage change | Standard Deviation 16.266 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 2 percentage change from OLP baseline | -23.55 Percentage change | Standard Deviation 7.652 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 5 percentage change from OLP baseline | -23.31 Percentage change | Standard Deviation 9.23 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 8 percentage change from OLP baseline | -22.01 Percentage change | Standard Deviation 10.037 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 12 percentage change from OLP baseline | -20.84 Percentage change | Standard Deviation 10.981 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 15 percentage change from OLP baseline | -21.18 Percentage change | Standard Deviation 10.351 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 19 percentage change from OLP baseline | -20.67 Percentage change | Standard Deviation 10.834 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 22 percentage change from OLP baseline | -19.67 Percentage change | Standard Deviation 11.723 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | Day 29 percentage change from OLP baseline | -21.42 Percentage change | Standard Deviation 11.659 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Mean Percentage Change in S-K Levels | EOS percentage change from OLP baseline | -8.54 Percentage change | Standard Deviation 12.405 |
| Placebo | Mean Percentage Change in S-K Levels | Day 5 percentage change from RTP baseline | 14.19 Percentage change | Standard Deviation 13.162 |
| Placebo | Mean Percentage Change in S-K Levels | Day 12 percentage change from OLP baseline | -4.57 Percentage change | Standard Deviation 10.335 |
| Placebo | Mean Percentage Change in S-K Levels | Day 22 percentage change from RTP baseline | 22.28 Percentage change | Standard Deviation 18.131 |
| Placebo | Mean Percentage Change in S-K Levels | EOS percentage change from OLP baseline | -5.95 Percentage change | Standard Deviation 11.927 |
| Placebo | Mean Percentage Change in S-K Levels | Day 15 percentage change from OLP baseline | -6.63 Percentage change | Standard Deviation 9.457 |
| Placebo | Mean Percentage Change in S-K Levels | Day 19 percentage change from RTP baseline | 22.77 Percentage change | Standard Deviation 14.583 |
| Placebo | Mean Percentage Change in S-K Levels | Day 29 percentage change from OLP baseline | -4.61 Percentage change | Standard Deviation 8.802 |
| Placebo | Mean Percentage Change in S-K Levels | Day 19 percentage change from OLP baseline | -4.89 Percentage change | Standard Deviation 9.279 |
| Placebo | Mean Percentage Change in S-K Levels | Day 15 percentage change from RTP baseline | 20.15 Percentage change | Standard Deviation 14.647 |
| Placebo | Mean Percentage Change in S-K Levels | Day 2 percentage change from RTP baseline | 4.19 Percentage change | Standard Deviation 10.592 |
| Placebo | Mean Percentage Change in S-K Levels | Day 22 percentage change from OLP baseline | -6.43 Percentage change | Standard Deviation 9.759 |
| Placebo | Mean Percentage Change in S-K Levels | Day 12 percentage change from RTP baseline | 22.87 Percentage change | Standard Deviation 16.457 |
| Placebo | Mean Percentage Change in S-K Levels | Day 2 percentage change from OLP baseline | -18.51 Percentage change | Standard Deviation 9.751 |
| Placebo | Mean Percentage Change in S-K Levels | EOS percentage change from RTP baseline | 20.70 Percentage change | Standard Deviation 17.035 |
| Placebo | Mean Percentage Change in S-K Levels | Day 8 percentage change from RTP baseline | 21.55 Percentage change | Standard Deviation 15.634 |
| Placebo | Mean Percentage Change in S-K Levels | Day 5 percentage change from OLP baseline | -10.96 Percentage change | Standard Deviation 9.724 |
| Placebo | Mean Percentage Change in S-K Levels | Day 29 percentage change from RTP baseline | 23.99 Percentage change | Standard Deviation 15.329 |
| Placebo | Mean Percentage Change in S-K Levels | Day 26 percentage change from OLP baseline | -4.74 Percentage change | Standard Deviation 9.551 |
| Placebo | Mean Percentage Change in S-K Levels | Day 8 percentage change from OLP baseline | -5.41 Percentage change | Standard Deviation 11.424 |
| Placebo | Mean Percentage Change in S-K Levels | Day 26 percentage change from RTP baseline | 23.63 Percentage change | Standard Deviation 15.353 |
Secondary
Number of Hyperkalemic Patients
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.
Time frame: Through 28-day randomized treatment phase.
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 5g | Number of Hyperkalemic Patients | 66 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Number of Hyperkalemic Patients | 45 Participants |
| Placebo | Number of Hyperkalemic Patients | 47 Participants |
Comparison: Results derived from a Cox Proportional Hazards model with the following covariates: treatment group, both baseline S-K values (48-hours open-label initial phase and double-blind randomized phase), baseline eGFR, age category (\<55, 55-64, \>=65 years), country, baseline RAAS inhibitor, chronic kidney, disease heart failure, and diabetes mellitus statuses.p-value: <0.00195% CI: [0.2954, 0.6631]Regression, Cox
p-value: <0.00195% CI: [0.0992, 0.2508]Regression, Cox
Secondary
Patient Reported Health State (EQ-5D) Questionnaire
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.
Time frame: Through study completion, an average of 37 days.
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 5g | Patient Reported Health State (EQ-5D) Questionnaire | OLP baseline | 75.0 Units on a scale | Standard Deviation 16.44 |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Patient Reported Health State (EQ-5D) Questionnaire | Day 29 | 77.6 Units on a scale | Standard Deviation 16.5 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Patient Reported Health State (EQ-5D) Questionnaire | OLP baseline | 74.3 Units on a scale | Standard Deviation 17.44 |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Patient Reported Health State (EQ-5D) Questionnaire | Day 29 | 76.9 Units on a scale | Standard Deviation 16.08 |
| Placebo | Patient Reported Health State (EQ-5D) Questionnaire | OLP baseline | 72.7 Units on a scale | Standard Deviation 17.32 |
| Placebo | Patient Reported Health State (EQ-5D) Questionnaire | Day 29 | 76.6 Units on a scale | Standard Deviation 14.08 |
Secondary
Percentage Change From Baseline in S-K Levels
Percentage change from baseline in S-K levels at all measured time intervals. The results in the table below are presented for OLP.
Time frame: Through 48-hour initial phase.
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | 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 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | 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 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | 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 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Percentage Change From Baseline in S-K Levels | OLP Day 2-24h percentage change | -14.08 Percentage change | Standard Deviation 6.479 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | 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 |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Percentage Change From Baseline in S-K Levels | OLP Day 3-48h percentage change | -22.16 Percentage change | Standard Deviation 7.812 |
Secondary
Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
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.
Time frame: Through 28-day randomized treatment phase.
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 5 | 71 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 19 | 55 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 2 | 89 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 8 | 62 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 26 | 56 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 1 | 93 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 12 | 62 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 22 | 54 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 29/Exit | 58 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 15 | 57 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 29 | 51 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 15 | 77 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 19 | 76 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 22 | 73 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 2 | 93 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 26 | 74 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 5 | 89 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 29/Exit | 77 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 8 | 81 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 12 | 78 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 1 | 94 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 29 | 71 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 29/Exit | 12 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 29 | 11 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 1 | 45 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 2 | 40 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 5 | 27 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 8 | 16 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 12 | 12 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 15 | 12 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 19 | 11 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 22 | 11 Participants |
| Placebo | Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit | Day 26 | 8 Participants |
Secondary
Proportion of Patients Achieving Normokalemia
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).
Time frame: Through 48-hour initial phase.
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Proportion of Patients Achieving Normokalemia | Normokalemic at 24h | 169 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Proportion of Patients Achieving Normokalemia | Not Normokalemic at 24h | 93 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Proportion of Patients Achieving Normokalemia | Missing at 24h | 5 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Proportion of Patients Achieving Normokalemia | Normokalemic at 48h | 238 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Proportion of Patients Achieving Normokalemia | Not Normokalemic at 48h | 22 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g Tid | Proportion of Patients Achieving Normokalemia | Missing at 48h | 7 Participants |
Secondary
Proportion of Patients Remaining Normokalemic
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.
Time frame: Through 28-day randomized treatment study phase day 8-29.
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sodium Zirconium Cyclosilicate (ZS) 5g | Proportion of Patients Remaining Normokalemic | 58 Participants |
| Sodium Zirconium Cyclosilicate (ZS) 10g | Proportion of Patients Remaining Normokalemic | 75 Participants |
| Placebo | Proportion of Patients Remaining Normokalemic | 12 Participants |
Comparison: Treatment group comparisons were made using a logistic regression model containing the following covariates: treatment group; both baseline S-K values (48-hours open-label initial phase and double-blind randomized phase); baseline eGFR (during 48-hour open-label initial phase); age category (\<55, 55-64, \>=65 years); country; baseline RAAS inhibitor, chronic kidney disease, heart failure, and diabetes mellitus statuses.p-value: <0.00195% CI: [2.6866, 14.9782]Regression, Logistic
p-value: <0.00195% CI: [7.1591, 46.2054]Regression, Logistic