Hyperkalemia
Conditions
Brief summary
It is hypothesized that ZS is more effective than placebo control (alternative hypothesis) in maintaining mean double-blind randomized maintenance phase (DBRMP) Day 8-29 serum potassium levels (3.5 - 5.0 mmol/l, inclusive) among hyperkalemic subjects in whom normokalemia was established during the open-label acute phase versus no difference between each ZS dose (highest to lowest) versus placebo control (null hypothesis).
Detailed description
Approximately 275 subjects with hyperkalemia (two consecutive i-STAT potassium levels ≥ 5.1 mmol/l, taken 60 minutes apart at baseline) will be enrolled in the Open-label Acute Phase to provide 232 subjects in the Double Blind Randomized Maintenance Phase. Initially all subjects will receive open-label ZS at a dose of 10g three times a day (tid) for 48 hours (AP). Subjects who achieve normokalemia (i-STAT potassium values between 3.5 to 5.0 mmol/l, inclusive) on the morning of Study Day 3 (after 6 doses of 10g ZS) will then, in a double-blind fashion, be randomized 4:4:4:7 to receive one of three doses of ZS (5g, 10g or 15g) or placebo control, qd for the following 28 days (DBRMP). Safety and tolerability will be assessed on an ongoing basis by an Independent Data Monitoring Committee (iDMC). Each active dose group in the DBRMP will consist of 49 subjects and the placebo control group will consist of 85 subjects for a total of 232 subjects to detect a 0.6 effect size difference between each ZS dose (from highest to lowest) and placebo control; the 4:4:4:7 allocation optimizes the multiple comparisons to the placebo control for the DBRMP.
Interventions
Sodium zirconium cyclosilicate
DRUGPlacebo
Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days (maintenance phase)
Sponsors
ZS Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent. * Over 18 years of age. * Two consecutive i-STAT potassium values, measured 60-minutes apart, both ≥5.1 mmol/l and measured within 1 day of the first ZS dose on AP Study Day 1. * Ability to have repeated blood draws or effective venous catheterization. * Women of childbearing potential must be using two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at AP Study Day 1. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential.
Exclusion criteria
* Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen, history of severe leukocytosis or thrombocytosis. * Subjects treated with lactulose, Xifaxan or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug. * Subjects treated with resins (such as sevelamer acetate or sodium polystyrene sulfonate \[SPS; e.g. Kayexalate®\]), calcium acetate, calcium carbonate, or lanthanum carbonate, within 7 days prior to the first dose of study drug. * Subjects with a life expectancy of less than 3 months. * Subjects 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. * Women who are pregnant, lactating, or planning to become pregnant. * Subjects with diabetic ketoacidosis. * Presence of any condition which, in the opinion of the investigator, places the subject 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. * Randomization into the previous ZS-002 or ZS-003 studies. * Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry. * Subjects with cardiac arrhythmias that require immediate treatment. * Subjects on dialysis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population). | 22 Days; Maintenance Phase Days 8 - 29, inclusive. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT). | 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) |
| Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit . | Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive. | — |
| Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive . | Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive. | — |
| Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. | Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive. | — |
| Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. | Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive. | — |
| Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L) | Maintenance Phase baseline to maintenance Phase Study Day 29/Exit. | — |
| Median Time to Normalization (3.50-5.0 mmol/L) in S-K Levels in the 48 Hours of Initial Treatment | Through 48 hours acute phase | — |
| Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | Maintenance Phase Study Days 1, 2, 5, 8, 12, 15, 19, 22, 26, 29, and 35, inclusive. | — |
| Median Time to Relapse in S-K Values | 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) |
| Exponential Rate of Change in S-K Values During the Acute Phase at 24 Hours and 48 Hours of Study Drug Treatment. | Acute Phase 24 hours and Acute Phase 48 hours. | — |
| Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. | All measured time intervals post dose during the Acute Phase. | — |
| Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase. | All measured time intervals post dose during the Acute Phase. | — |
| Proportion of Subjects Who Achieve Normokalemia During the Acute Phase at 24 and 48 Hours After Start of Dosing | Through 48 hours acute phase | — |
| Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8 | 22 days; Maintenance Phase Day 8 - 29 | — |
Countries
Australia, South Africa, United States
Participant flow
Recruitment details
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
Pre-assignment details
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 \[MP\]).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 258 |
| Placebo Comparator (Maintenance Phase) Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive. | 85 |
| 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. | 45 |
| 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. | 51 |
| 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. | 56 |
| Total | 495 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Acute Phase | Hyperkalemia | 2 | 0 | 0 | 0 | 0 |
| Acute Phase | Withdrawal by Subject | 5 | 0 | 0 | 0 | 0 |
| Maintanance Phase | Adverse Event | 0 | 0 | 3 | 0 | 1 |
| Maintanance Phase | Hypo- or hyperkalemia | 0 | 3 | 0 | 3 | 1 |
| Maintanance Phase | Met ECG withdrawal criteria | 0 | 0 | 1 | 0 | 2 |
| Maintanance Phase | Miscellaneous | 0 | 2 | 1 | 2 | 1 |
| Maintanance Phase | Physician Decision | 0 | 0 | 0 | 0 | 1 |
| Maintanance Phase | Sponsor's decision | 0 | 2 | 0 | 2 | 1 |
| Maintanance Phase | Subject compliance | 0 | 1 | 0 | 0 | 0 |
| Maintanance Phase | Withdrawal by Subject | 0 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo Comparator (Maintenance Phase) | ZS 10 g Three Times Daily (Acute Phase) | Total | ZS 15 g Once Daily (Maintenance Phase) | ZS 10 g Once Daily (Maintenance Phase) | ZS 5 g Once Daily (Maintenance Phase) |
|---|---|---|---|---|---|---|
| Age, Continuous Acute Phase | NA Years | 64.0 Years STANDARD_DEVIATION 12.72 | 64.0 Years STANDARD_DEVIATION 12.72 | NA Years | NA Years | NA Years |
| Age, Continuous Maintenance Phase | 64.3 Years STANDARD_DEVIATION 12.13 | NA Years | 63.80 Years STANDARD_DEVIATION 13.01 | 64.9 Years STANDARD_DEVIATION 12.85 | 63.8 Years STANDARD_DEVIATION 9.97 | 61.5 Years STANDARD_DEVIATION 16.89 |
| Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases 5.5-<6.0 mmol/L, Acute Phase | 0 Participants | 100 Participants | 100 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases 5.5-<6.0 mmol/L, Maintenance Phase | 30 Participants | 0 Participants | 96 Participants | 26 Participants | 23 Participants | 17 Participants |
| Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases <5.5 mmol/L, Acute Phase | 0 Participants | 119 Participants | 119 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases <5.5 mmol/L, Maintenance Phase | 43 Participants | 0 Participants | 109 Participants | 24 Participants | 19 Participants | 23 Participants |
| Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases ≥ 6.0 mmol/L, Acute Phase | 0 Participants | 39 Participants | 39 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases ≥ 6.0 mmol/L, Maintenance Phase | 12 Participants | 0 Participants | 32 Participants | 6 Participants | 9 Participants | 5 Participants |
| eGFR at baseline during both the Acute and Maintenance phases <60 mL/min, Acute Phase | 0 Participants | 179 Participants | 179 Participants | 0 Participants | 0 Participants | 0 Participants |
| eGFR at baseline during both the Acute and Maintenance phases ≥ 60 mL/min, Acute Phase | 0 Participants | 72 Participants | 72 Participants | 0 Participants | 0 Participants | 0 Participants |
| eGFR at baseline during both the Acute and Maintenance phases <60 mL/min, Maintenance Phase | 52 Participants | 0 Participants | 162 Participants | 41 Participants | 38 Participants | 31 Participants |
| eGFR at baseline during both the Acute and Maintenance phases ≥ 60 mL/min, Maintenance Phase | 28 Participants | 0 Participants | 68 Participants | 15 Participants | 13 Participants | 12 Participants |
| eGFR at baseline during both the Acute and Maintenance phases Not reported, Acute Phase | 0 Participants | 7 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants |
| eGFR at baseline during both the Acute and Maintenance phases Not reported, Maintenance Phase | 5 Participants | 0 Participants | 7 Participants | 0 Participants | 0 Participants | 2 Participants |
| Etiology of elevated S-K levels during both the Acute and Maintenance phases Chronic kidney disease, Acute Phase | 0 Participants | 169 Participants | 169 Participants | 0 Participants | 0 Participants | 0 Participants |
| Etiology of elevated S-K levels during both the Acute and Maintenance phases Chronic kidney disease, Maintenance Phase | 50 Participants | 0 Participants | 152 Participants | 37 Participants | 36 Participants | 29 Participants |
| Etiology of elevated S-K levels during both the Acute and Maintenance phases Diabetes mellitus, Acute Phase | 0 Participants | 170 Participants | 170 Participants | 0 Participants | 0 Participants | 0 Participants |
| Etiology of elevated S-K levels during both the Acute and Maintenance phases Diabetes mellitus, Maintenance Phase | 54 Participants | 0 Participants | 157 Participants | 39 Participants | 38 Participants | 26 Participants |
| Etiology of elevated S-K levels during both the Acute and Maintenance phases Heart failure, Acute Phase | 0 Participants | 94 Participants | 94 Participants | 0 Participants | 0 Participants | 0 Participants |
| Etiology of elevated S-K levels during both the Acute and Maintenance phases Heart failure, Maintenance Phase | 26 Participants | 0 Participants | 87 Participants | 25 Participants | 18 Participants | 18 Participants |
| Etiology of elevated S-K levels during both the Acute and Maintenance phases RAAS inhibitor medication, Acute Phase | 0 Participants | 180 Participants | 180 Participants | 0 Participants | 0 Participants | 0 Participants |
| Etiology of elevated S-K levels during both the Acute and Maintenance phases RAAS inhibitor medication, Maintenance Phase | 61 Participants | 0 Participants | 163 Participants | 33 Participants | 36 Participants | 33 Participants |
| Race/Ethnicity, Customized Asian, Acute Phase | 0 Participants | 5 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian, Maintenance Phase | 3 Participants | 0 Participants | 5 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American, Acute Phase | 0 Participants | 37 Participants | 37 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American, Maintenance Phase | 10 Participants | 0 Participants | 32 Participants | 9 Participants | 5 Participants | 8 Participants |
| Race/Ethnicity, Customized Multiple Races indicated, Acute Phase | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Multiple Races indicated, Maintenance Phase | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander, AP | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander, MP | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other, Acute Phase | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other, Maintenance Phase | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White, Acute Phase | 0 Participants | 215 Participants | 215 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White, Maintenance Phase | 73 Participants | 0 Participants | 199 Participants | 46 Participants | 44 Participants | 36 Participants |
| Sex/Gender, Customized Female, Acute Phase | 0 Participants | 109 Participants | 109 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex/Gender, Customized Female, Maintenance Phase | 41 Participants | 0 Participants | 99 Participants | 16 Participants | 24 Participants | 18 Participants |
| Sex/Gender, Customized Male, Acute Phase | 0 Participants | 149 Participants | 149 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex/Gender, Customized Male, Maintenance Phase | 44 Participants | 0 Participants | 138 Participants | 40 Participants | 27 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 258 | 25 / 85 | 20 / 45 | 15 / 51 | 25 / 56 |
| serious Total, serious adverse events | 0 / 258 | 0 / 85 | 5 / 45 | 2 / 51 | 3 / 56 |
Outcome results
Primary
Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population).
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo Comparator (Maintenance Phase) | Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population). | 5.0603 mmol/L |
| ZS 5 g Once Daily (Maintenance Phase) | Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population). | 4.7544 mmol/L |
| ZS 10 g Once Daily (Maintenance Phase) | Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population). | 4.5081 mmol/L |
| ZS 15 g Once Daily (Maintenance Phase) | Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population). | 4.3742 mmol/L |
Secondary
Exponential Rate of Change in S-K Values During the Acute Phase at 24 Hours and 48 Hours of Study Drug Treatment.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 0.00013 |
Secondary
Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.
Time frame: All measured time intervals post dose during the Acute Phase.
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 0.44 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 0.51 |
Secondary
Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit .
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -0.72 mmol/L | Standard Deviation 0.552 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -0.69 mmol/L | Standard Deviation 0.5 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -0.75 mmol/L | Standard Deviation 0.516 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -0.77 mmol/L | Standard Deviation 0.492 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -0.79 mmol/L | Standard Deviation 0.52 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -0.71 mmol/L | Standard Deviation 0.543 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -0.77 mmol/L | Standard Deviation 0.559 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -0.65 mmol/L | Standard Deviation 0.448 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 5.53 mmol/L | Standard Deviation 0.357 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -1.03 mmol/L | Standard Deviation 0.408 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -0.87 mmol/L | Standard Deviation 0.697 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -0.93 mmol/L | Standard Deviation 0.653 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -1.10 mmol/L | Standard Deviation 0.813 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 5.58 mmol/L | Standard Deviation 0.423 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -1.11 mmol/L | Standard Deviation 0.663 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -1.04 mmol/L | Standard Deviation 0.581 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -1.08 mmol/L | Standard Deviation 0.704 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -1.25 mmol/L | Standard Deviation 0.471 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -1.11 mmol/L | Standard Deviation 0.652 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -1.09 mmol/L | Standard Deviation 0.629 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.19 mmol/L | Standard Deviation 0.627 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.03 mmol/L | Standard Deviation 0.597 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.07 mmol/L | Standard Deviation 0.575 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.19 mmol/L | Standard Deviation 0.659 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.05 mmol/L | Standard Deviation 0.586 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.12 mmol/L | Standard Deviation 0.477 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.20 mmol/L | Standard Deviation 0.592 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.20 mmol/L | Standard Deviation 0.665 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 0.331 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.12 mmol/L | Standard Deviation 0.571 |
Secondary
Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.
Time frame: Maintenance phase baseline to Maintenance Phase Study 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 0.58 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 0.30 mmol/L | Standard Deviation 0.467 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 0.28 mmol/L | Standard Deviation 0.664 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 0.22 mmol/L | Standard Deviation 0.58 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 0.25 mmol/L | Standard Deviation 0.645 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -0.01 mmol/L | Standard Deviation 0.372 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 0.30 mmol/L | Standard Deviation 0.563 |
| ZS 5 g Once Daily (Maintenance Phase) | Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. | MP Baseline S-K level | 4.51 mmol/L | Standard Deviation 0.357 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 0.25 mmol/L | Standard Deviation 0.535 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 0.26 mmol/L | Standard Deviation 0.541 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 0.34 mmol/L | Standard Deviation 0.565 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 0.10 mmol/L | Standard Deviation 0.594 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 0.14 mmol/L | Standard Deviation 0.668 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 0.11 mmol/L | Standard Deviation 0.768 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 0.12 mmol/L | Standard Deviation 0.523 |
| ZS 10 g Once Daily (Maintenance Phase) | Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. | MP Baseline S-K level | 4.38 mmol/L | Standard Deviation 0.407 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 0.33 mmol/L | Standard Deviation 0.673 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 0.11 mmol/L | Standard Deviation 0.552 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 0.17 mmol/L | Standard Deviation 0.483 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 0.27 mmol/L | Standard Deviation 0.65 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -0.04 mmol/L | Standard Deviation 0.384 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -0.09 mmol/L | Standard Deviation 0.598 |
| ZS 15 g Once Daily (Maintenance Phase) | Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit. | MP Baseline S-K level | 4.45 mmol/L | Standard Deviation 0.372 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -0.02 mmol/L | Standard Deviation 0.4 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -0.10 mmol/L | Standard Deviation 0.535 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -0.11 mmol/L | Standard Deviation 0.572 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -0.10 mmol/L | Standard Deviation 0.546 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | 0.01 mmol/L | Standard Deviation 0.605 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | 0.03 mmol/L | Standard Deviation 0.579 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | 0.05 mmol/L | Standard Deviation 0.594 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -0.04 mmol/L | Standard Deviation 0.554 |
Secondary
Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.
Time frame: All measured time intervals post dose during the Acute Phase.
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 7.72 |
| Placebo Comparator (Maintenance Phase) | 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
Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive .
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 8.94 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -14.08 Percent Change | Standard Deviation 8.822 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -11.83 Percent Change | Standard Deviation 8.025 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -12.65 Percent Change | Standard Deviation 9.591 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -12.84 Percent Change | Standard Deviation 9.7 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -18.53 Percent Change | Standard Deviation 6.941 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -13.36 Percent Change | Standard Deviation 8.949 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -13.85 Percent Change | Standard Deviation 9.568 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -12.49 Percent Change | Standard Deviation 8.77 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | -13.73 Percent Change | Standard Deviation 8.485 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -18.29 Percent Change | Standard Deviation 9.707 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -22.19 Percent Change | Standard Deviation 7.897 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -19.16 Percent Change | Standard Deviation 10.708 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -19.45 Percent Change | Standard Deviation 11.072 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -19.33 Percent Change | Standard Deviation 10.884 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -16.25 Percent Change | Standard Deviation 11.292 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -15.18 Percent Change | Standard Deviation 11.988 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -18.83 Percent Change | Standard Deviation 11.951 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -19.28 Percent Change | Standard Deviation 14.099 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -18.28 Percent Change | Standard Deviation 10.271 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -21.19 Percent Change | Standard Deviation 10.675 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -21.22 Percent Change | Standard Deviation 11.368 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -21.06 Percent Change | Standard Deviation 11.086 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -19.80 Percent Change | Standard Deviation 9.503 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -21.29 Percent Change | Standard Deviation 10.135 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -18.65 Percent Change | Standard Deviation 10.034 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -19.10 Percent Change | Standard Deviation 9.957 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -20.04 Percent Change | Standard Deviation 7.959 |
Secondary
Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.
Time frame: Maintenance phase baseline to Maintenance Phase Study 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 5.33 Percent Change | Standard Deviation 12.934 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 7.98 Percent Change | Standard Deviation 12.932 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 6.98 Percent Change | Standard Deviation 12.774 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 6.93 Percent Change | Standard Deviation 10.486 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 0.06 Percent Change | Standard Deviation 8.036 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 6.38 Percent Change | Standard Deviation 12.287 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 6.12 Percent Change | Standard Deviation 14.424 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 6.12 Percent Change | Standard Deviation 14.424 |
| ZS 5 g Once Daily (Maintenance Phase) | 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 | 5.95 Percent Change | Standard Deviation 12.169 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 4.28 Percent Change | Standard Deviation 11.231 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | -0.51 Percent Change | Standard Deviation 8.862 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 3.05 Percent Change | Standard Deviation 12.346 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 2.85 Percent Change | Standard Deviation 13.595 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 2.93 Percent Change | Standard Deviation 12.662 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 6.79 Percent Change | Standard Deviation 15.174 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 8.08 Percent Change | Standard Deviation 15.516 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 3.02 Percent Change | Standard Deviation 17.785 |
| ZS 10 g Once Daily (Maintenance Phase) | 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 | 3.02 Percent Change | Standard Deviation 17.785 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | 1.88 Percent Change | Standard Deviation 16.641 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.89 Percent Change | Standard Deviation 12.118 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -2.00 Percent Change | Standard Deviation 12.836 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.43 Percent Change | Standard Deviation 13.664 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.43 Percent Change | Standard Deviation 13.664 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -1.74 Percent Change | Standard Deviation 12.043 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | 1.39 Percent Change | Standard Deviation 12.782 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | .095 Percent Change | Standard Deviation 13.697 |
| ZS 15 g Once Daily (Maintenance Phase) | 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 | -0.20 Percent Change | Standard Deviation 8.984 |
Secondary
Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo Comparator (Maintenance Phase) | 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 |
| ZS 5 g Once Daily (Maintenance Phase) | Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8 | 0.06367 mmol/L |
| ZS 10 g Once Daily (Maintenance Phase) | Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8 | 0.07708 mmol/L |
| ZS 15 g Once Daily (Maintenance Phase) | Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8 | 0.06849 mmol/L |
Secondary
Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L)
Time frame: Maintenance Phase baseline to maintenance Phase Study Day 29/Exit.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Comparator (Maintenance Phase) | Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L) | 7 Days |
| ZS 5 g Once Daily (Maintenance Phase) | Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L) | 14 Days |
| ZS 10 g Once Daily (Maintenance Phase) | Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L) | NA Days |
| ZS 15 g Once Daily (Maintenance Phase) | Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L) | NA Days |
Secondary
Median Time to Normalization (3.50-5.0 mmol/L) in S-K Levels in the 48 Hours of Initial Treatment
Time frame: Through 48 hours acute phase
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Comparator (Maintenance Phase) | Median Time to Normalization (3.50-5.0 mmol/L) in S-K Levels in the 48 Hours of Initial Treatment | 2.17 Hours |
Secondary
Median Time to Relapse in S-K Values
Median time to relapse in S-K values (return to original Acute Phase S-K baseline value)
Time frame: Maintenance phase Study Day 1 to Study Day 29/Exit.
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Comparator (Maintenance Phase) | Median Time to Relapse in S-K Values | 19 Days |
| ZS 5 g Once Daily (Maintenance Phase) | Median Time to Relapse in S-K Values | 29 Days |
| ZS 10 g Once Daily (Maintenance Phase) | Median Time to Relapse in S-K Values | NA Days |
| ZS 15 g Once Daily (Maintenance Phase) | Median Time to Relapse in S-K Values | NA Days |
Secondary
Proportion of Subjects Who Achieve Normokalemia During the Acute Phase at 24 and 48 Hours After Start of Dosing
Time frame: Through 48 hours acute phase
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | 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 |
| Placebo Comparator (Maintenance Phase) | 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
Proportion of Subjects Who Remained Normokalemic During Maintenance Phase
Time frame: Maintenance Phase Study Days 1, 2, 5, 8, 12, 15, 19, 22, 26, 29, and 35, 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 29/Exit | 0.476 Proportion of subjects |
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 26 | 0.486 Proportion of subjects |
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 19 | 0.449 Proportion of subjects |
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 2 | 0.84 Proportion of subjects |
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 22 | 0.442 Proportion of subjects |
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | Baseline | 0.866 Proportion of subjects |
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 8 | 0.481 Proportion of subjects |
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 29 | 0.507 Proportion of subjects |
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 12 | 0.400 Proportion of subjects |
| Placebo Comparator (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 15 | 0.438 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 29/Exit | 0.711 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 8 | 0.711 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | Baseline | 0.933 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 19 | 0.744 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 26 | 0.738 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 22 | 0.674 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 15 | 0.705 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 2 | 0.933 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 12 | 0.750 Proportion of subjects |
| ZS 5 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 29 | 0.667 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 15 | 0.851 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | Baseline | 0.920 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 2 | 0.918 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 8 | 0.820 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 12 | 0.787 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 29/Exit | 0.760 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 19 | 0.787 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 22 | 0.667 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 26 | 0.711 Proportion of subjects |
| ZS 10 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 29 | 0.816 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 15 | 0.827 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 12 | 0.849 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | Baseline | 0.926 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 26 | 0.843 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 8 | 0.852 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 2 | 0.944 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 29/Exit | 0.852 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 19 | 0.882 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 29 | 0.907 Proportion of subjects |
| ZS 15 g Once Daily (Maintenance Phase) | Proportion of Subjects Who Remained Normokalemic During Maintenance Phase | MP Study Day 22 | 0.882 Proportion of subjects |
Secondary
The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT).
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)
Time frame: 22 days; Maintenance Phase Day 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Comparator (Maintenance Phase) | The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT). | 7.4 Days | Standard Deviation 8 |
| ZS 5 g Once Daily (Maintenance Phase) | The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT). | 13.4 Days | Standard Deviation 7.57 |
| ZS 10 g Once Daily (Maintenance Phase) | The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT). | 13.9 Days | Standard Deviation 7.91 |
| ZS 15 g Once Daily (Maintenance Phase) | The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT). | 16.8 Days | Standard Deviation 6.99 |