Chronic Kidney Disease, Hyperkalemia, Kidney Dysfunction
Conditions
Brief summary
It is hypothesized that zirconium silicate is safe and well tolerated and more effective than placebo (alternative hypothesis) in lowering serum potassium levels in subjects with serum potassium between 5 - 6.0 mmol/l versus no difference between zirconium silicate and placebo (null hypothesis). It is hypothesized that zirconium silicate even up to the top dose of 10g three times a day is well tolerated.
Detailed description
A total of 90 subjects with moderate CKD (defined as GFR between 40- 60ml/min) and mild hyperkalemia (S-K between 5-6 mmol/l) will be enrolled in the study where, in a double-blind dose-escalating fashion (three separate cohorts), they will be randomized to receive one of the doses of ZS (0.3g, 3g and 10g) or placebo, administered 3 times (tid) daily with meals. The first cohort will have 18 subjects while both of the second and third cohorts will have 36 subjects for a total of 90 subjects. Safety and tolerability will be assessed by an Independent Data Safety Monitoring Board (DSMB) after completion of each cohort, before escalation to the next dose level will be allowed. The next dose escalation will happen no sooner than one week after the last dose of study drug at the previous dosing level has been administered. Safety stopping rules will be specified for this study. Within the first dose level (300 mg dose), 12 subjects will be randomized to receive ZS, whereas 6 subjects will be randomized to receive placebo for a total of 18 subjects in this first cohort. In the next two cohorts (3 g and 10 g doses), 24 subjects per cohort will be randomized to receive ZS, whereas 12 subjects per cohort will be randomized to receive placebo for a total of 36 subjects in each of the second and third cohorts.
Interventions
DRUGZirconium silicate (ZS)
Randomized escalating doses (0.3g, 3g and 10g) of ZS (fractionated, protonated microporous Zirconium Silicate, an oral sorbent) administered 3 times daily (tid) with meals.
DRUGPlacebo
Randomized to mimic escalating doses of experimental drug administered 3 times daily (tid) with meals.
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. * GFR between 40-60 ml/min as estimated by the CKD-EPI equation. After screening two additional GFR values of between 40-60ml/min must be repeated within 24 hours before inclusion is allowed. * S-K between 5.0 - 6.0 mmol/l (inclusive) during Study Day 0. * Ability to have repeated blood draws or effective venous catheterization. * Women of child bearing potential must be practicing a highly effective method of birth control.
Exclusion criteria
* Pseudohyperkalemia such as excessive fist clinching hemolyzed blood specimen, severe leukocytosis or thrombocytosis. * Subjects treated with lactulose, xifaxan or other non-absorbed antibiotics for hyperammonemia within the last 7 days. * Subjects treated with resins (such as sevelamer acetate, calcium acetate or calcium carbonate, lanthanum carbonate, Sodium polystyrene sulfonate (SPS; e.g. Kayexalate®) within the last 7 days. * Subjects with a life expectancy of less than 3 months. * Subjects who are HIV positive. * 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 Ketoacidosis/Acidemia. * Cancer within the last 5 years (other than successfully treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or early stage prostate cancer). * 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 Zirconium Silicate or to components thereof. * Subjects who have cardiac arrhythmias that require immediate treatment. * Subjects with ECG changes associated with hyperkalemia. * Subjects with acute kidney injury.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment | 24 and 48 hours post first study drug dose | The rate of fall in S-K levels during the initial 48 hours of study drug treatment between the placebo treated subjects and the ZS treated subjects measured on a log scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Specific S-K Levels to Normalization | 48 and 72 hours post first study drug dose | Percent of subjects achieving S-K normalization (\<=as defined by S-K levels of 3.5 to 4.9 mmol/L) from baseline at Study Days 2 and 3 at 0 hr. |
| Time Specific Decreases in S-K Levels of > = 0.5 mmol/L | 24 and 48 hours post first study drug dose | Percentage of participants achieving a 0.5mmol/L drop from baseline at Study Days 2 and 3 at 0 hr. |
| Percentage of Participants With Normal S-K Levels at End of Study Day 2 | 48 hours post first study drug dose | Percentage (%) of subjects who achieve S-K normalization at end of Study Day 2 |
| Urine Sodium Excretion | 24 and 48 hours post first study drug dose | Urine sodium excretion compared between the combined placebo-treated controls and the ZS-treated subjects (measured throughout two 24-hour periods on Study Days 1 and 2). |
| Urine Potassium Excretion | 24 and 48 hours post study drug dose | Urine potassium excretion compared between the combined placebo-treated controls and the ZS-treated subjects (measured throughout two 24-hour periods on Study Days 1 and 2). |
| Urea Nitrogen Excretion | 24 and 48 hours post study drug dose | Urea nitrogen excretion compared between the combined placebo-treated controls and the ZS-treated subjects (measured throughout two 24-hour periods on Study Days 1 and 2). |
| Blood Urea Nitrogen | 24 and 48 hours post study drug dose | Blood urea nitrogen compared between the combined placebo-treated controls and the ZS-treated subjects (measured 24 & 48 hours post dose on Study Days 2 and 3). |
| Serum Potassium (S-K) at Individual Time Points. | First 48 hours of study | Serum potassium (S-K) at individual time points through Study day 3/0hour. |
| Serum Calcium (S-Ca) Levels | 24 and 48 hours post study drug dose | Serum calcium compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 & 48 hours post dose on Study Days 2 and 3). |
| Serum Sodium (S-Na) Levels | 24 and 48 hours post study drug dose | Serum sodium compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 & 48 hours post dose on Study Days 2 and 3). |
| Serum Bicarbonate (HCO3) Levels | 24 and 48 hours post study drug dose | Serum bicarbonate compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 & 48 hours post dose on Study Days 2 and 3). |
| 24-hour Urinary Excretion of Potassium | 24 and 48 hours post study drug dose | 24-hour urinary excretion of potassium on Study Days 1 and Day 2 |
| 24-hour Urinary Excretion of Sodium | 48 hours | 24-hour urinary excretion of sodium on Study Days 1 and Day 2 |
| 24-hour Urinary Excretion of Urea Nitrogen | 48 hours | 24-hour urinary excretion of urea nitrogen on Study Days 1 and Day 2 |
| 24-hour Urinary Excretion of Creatinine | 48 hours | 24-hour urinary excretion of creatinine on Study Days 1 and Day 2 |
| Serum Magnesium (S-Mg) Levels | 24 and 48 hours post study drug dose | Serum magnesium compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 & 48 hours post dose on Study Days 2 and 3). |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 9 centers in the United States from 28 November 2011 to 22 May 2012.
Pre-assignment details
Combined Placebo Group
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo randomized to mimic escalating doses of experimental drug administered three times daily . | 30 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water | 12 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water | 24 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water | 24 |
| Total | 90 |
Baseline characteristics
| Characteristic | Placebo | Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Total |
|---|---|---|---|---|---|
| Age, Continuous | 69.7 Years STANDARD_DEVIATION 11 | 70.3 Years STANDARD_DEVIATION 6.9 | 72.0 Years STANDARD_DEVIATION 6.3 | 72.3 Years STANDARD_DEVIATION 11.7 | 71.1 Years STANDARD_DEVIATION 9.59 |
| GFR at Study Day 0 | 45.6 mL/min/1.73 m^2 STANDARD_DEVIATION 9.05 | 46.2 mL/min/1.73 m^2 STANDARD_DEVIATION 4.99 | 46.8 mL/min/1.73 m^2 STANDARD_DEVIATION 7.14 | 43.5 mL/min/1.73 m^2 STANDARD_DEVIATION 9.01 | 45.4 mL/min/1.73 m^2 STANDARD_DEVIATION 8.09 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 29 Participants | 12 Participants | 24 Participants | 23 Participants | 88 Participants |
| Serum potassium | 5.19 mmol/L STANDARD_DEVIATION 0.301 | 5.25 mmol/L STANDARD_DEVIATION 0.144 | 5.11 mmol/L STANDARD_DEVIATION 0.328 | 5.13 mmol/L STANDARD_DEVIATION 0.378 | 5.16 mmol/L STANDARD_DEVIATION 0.314 |
| Sex/Gender, Customized Female | 7 Participants | 6 Participants | 10 Participants | 15 Participants | 38 Participants |
| Sex/Gender, Customized Male | 23 Participants | 6 Participants | 14 Participants | 9 Participants | 52 Participants |
| Weight at baseline | 95.15 kilograms STANDARD_DEVIATION 22.122 | 84.76 kilograms STANDARD_DEVIATION 18.022 | 88.96 kilograms STANDARD_DEVIATION 22.002 | 86.59 kilograms STANDARD_DEVIATION 26.311 | 89.83 kilograms STANDARD_DEVIATION 22.794 |
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 / 30 | 0 / 12 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 3 / 30 | 1 / 12 | 3 / 24 | 8 / 24 |
| serious Total, serious adverse events | 0 / 30 | 0 / 12 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment
The rate of fall in S-K levels during the initial 48 hours of study drug treatment between the placebo treated subjects and the ZS treated subjects measured on a log scale
Time frame: 24 and 48 hours post first study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment | Day2/0 Hr ( 24 hours) | 0 log(mmol/L/hour) | — |
| Placebo (Combined All Three Cohorts) | Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment | Day 3/0 Hr (48 hours) | 0 log(mmol/L/hour) | — |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment | Day 3/0 Hr (48 hours) | -0.00045 log(mmol/L/hour) | Standard Error 0.000555 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment | Day2/0 Hr ( 24 hours) | -0.00035 log(mmol/L/hour) | Standard Error 0.001166 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment | Day2/0 Hr ( 24 hours) | -0.00169 log(mmol/L/hour) | Standard Error 0.000932 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment | Day 3/0 Hr (48 hours) | -0.00089 log(mmol/L/hour) | Standard Error 0.000444 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment | Day2/0 Hr ( 24 hours) | -0.000143 log(mmol/L/hour) | Standard Error 0.000932 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment | Day 3/0 Hr (48 hours) | -0.00256 log(mmol/L/hour) | Standard Error 0.000444 |
Secondary
24-hour Urinary Excretion of Creatinine
24-hour urinary excretion of creatinine on Study Days 1 and Day 2
Time frame: 48 hours
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Creatinine | Day 2 | 1270.71 mg/24 hour | Standard Deviation 544.596 |
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Creatinine | Baseline | 1175.39 mg/24 hour | Standard Deviation 482.708 |
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Creatinine | Day 1 | 1157.12 mg/24 hour | Standard Deviation 506.515 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Creatinine | Day 1 | 1027.50 mg/24 hour | Standard Deviation 301.315 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Creatinine | Baseline | 1149.00 mg/24 hour | Standard Deviation 483.74 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Creatinine | Day 2 | 1092.23 mg/24 hour | Standard Deviation 411.469 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Creatinine | Day 2 | 1050.29 mg/24 hour | Standard Deviation 344.882 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Creatinine | Baseline | 1126.26 mg/24 hour | Standard Deviation 446.745 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Creatinine | Day 1 | 996.45 mg/24 hour | Standard Deviation 442.333 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Creatinine | Day 1 | 1008.25 mg/24 hour | Standard Deviation 428.524 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Creatinine | Baseline | 1015.67 mg/24 hour | Standard Deviation 471.275 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Creatinine | Day 2 | 1028.79 mg/24 hour | Standard Deviation 430.408 |
Secondary
24-hour Urinary Excretion of Potassium
24-hour urinary excretion of potassium on Study Days 1 and Day 2
Time frame: 24 and 48 hours post study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Potassium | Baseline | 56.5 mmol/24 hour | Standard Deviation 33.96 |
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Potassium | Study Day 2 | 65.4 mmol/24 hour | Standard Deviation 29.23 |
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Potassium | Study Day 1 | 64.7 mmol/24 hour | Standard Deviation 28.02 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Potassium | Baseline | 62.4 mmol/24 hour | Standard Deviation 31.51 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Potassium | Study Day 2 | 86.6 mmol/24 hour | Standard Deviation 52.64 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Potassium | Study Day 1 | 89.4 mmol/24 hour | Standard Deviation 46.62 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Potassium | Study Day 1 | 60.5 mmol/24 hour | Standard Deviation 25.42 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Potassium | Baseline | 58.9 mmol/24 hour | Standard Deviation 20.44 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Potassium | Study Day 2 | 58.1 mmol/24 hour | Standard Deviation 24.77 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Potassium | Baseline | 46.9 mmol/24 hour | Standard Deviation 23.67 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Potassium | Study Day 2 | 31.1 mmol/24 hour | Standard Deviation 16.55 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Potassium | Study Day 1 | 41.0 mmol/24 hour | Standard Deviation 20.49 |
Secondary
24-hour Urinary Excretion of Sodium
24-hour urinary excretion of sodium on Study Days 1 and Day 2
Time frame: 48 hours
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Sodium | Baseline | 145 mmol/24 hour | Standard Deviation 93.05 |
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Sodium | Study Day 2 | 181.8 mmol/24 hour | Standard Deviation 101.42 |
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Sodium | Study Day 1 | 169.4 mmol/24 hour | Standard Deviation 88.9 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Sodium | Baseline | 132.8 mmol/24 hour | Standard Deviation 51.09 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Sodium | Study Day 2 | 181.5 mmol/24 hour | Standard Deviation 101.63 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Sodium | Study Day 1 | 173.7 mmol/24 hour | Standard Deviation 64.02 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Sodium | Study Day 1 | 136.6 mmol/24 hour | Standard Deviation 79.5 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Sodium | Baseline | 124.0 mmol/24 hour | Standard Deviation 46.24 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Sodium | Study Day 2 | 132.5 mmol/24 hour | Standard Deviation 63.06 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Sodium | Baseline | 114.8 mmol/24 hour | Standard Deviation 49 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Sodium | Study Day 2 | 140.2 mmol/24 hour | Standard Deviation 66.86 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Sodium | Study Day 1 | 141.0 mmol/24 hour | Standard Deviation 68.05 |
Secondary
24-hour Urinary Excretion of Urea Nitrogen
24-hour urinary excretion of urea nitrogen on Study Days 1 and Day 2
Time frame: 48 hours
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Urea Nitrogen | Baseline | 7.66 g/24 hour | Standard Deviation 3.622 |
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Urea Nitrogen | Day 2 | 10.37 g/24 hour | Standard Deviation 6.585 |
| Placebo (Combined All Three Cohorts) | 24-hour Urinary Excretion of Urea Nitrogen | Day 1 | 8.30 g/24 hour | Standard Deviation 3.832 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Urea Nitrogen | Baseline | 7.59 g/24 hour | Standard Deviation 2.768 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Urea Nitrogen | Day 2 | 8.68 g/24 hour | Standard Deviation 2.475 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | 24-hour Urinary Excretion of Urea Nitrogen | Day 1 | 8.51 g/24 hour | Standard Deviation 5.549 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Urea Nitrogen | Day 1 | 7.99 g/24 hour | Standard Deviation 3.929 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Urea Nitrogen | Baseline | 7.03 g/24 hour | Standard Deviation 2.679 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | 24-hour Urinary Excretion of Urea Nitrogen | Day 2 | 8.57 g/24 hour | Standard Deviation 3.453 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Urea Nitrogen | Baseline | 6.74 g/24 hour | Standard Deviation 2.618 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Urea Nitrogen | Day 2 | 7.49 g/24 hour | Standard Deviation 3.077 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | 24-hour Urinary Excretion of Urea Nitrogen | Day 1 | 7.80 g/24 hour | Standard Deviation 3.46 |
Secondary
Blood Urea Nitrogen
Blood urea nitrogen compared between the combined placebo-treated controls and the ZS-treated subjects (measured 24 & 48 hours post dose on Study Days 2 and 3).
Time frame: 24 and 48 hours post study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Blood Urea Nitrogen | Baseline | 24.50 mg/dL | Standard Deviation 7.481 |
| Placebo (Combined All Three Cohorts) | Blood Urea Nitrogen | Day 3/0Hr | 24.50 mg/dL | Standard Deviation 7.284 |
| Placebo (Combined All Three Cohorts) | Blood Urea Nitrogen | Day 2/)0Hr | 24.05 mg/dL | Standard Deviation 7.626 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Blood Urea Nitrogen | Baseline | 23.52 mg/dL | Standard Deviation 8.217 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Blood Urea Nitrogen | Day 3/0Hr | 23.33 mg/dL | Standard Deviation 7.895 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Blood Urea Nitrogen | Day 2/)0Hr | 23.63 mg/dL | Standard Deviation 7.241 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Blood Urea Nitrogen | Day 2/)0Hr | 23.98 mg/dL | Standard Deviation 7.619 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Blood Urea Nitrogen | Baseline | 25.16 mg/dL | Standard Deviation 8.065 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Blood Urea Nitrogen | Day 3/0Hr | 24.04 mg/dL | Standard Deviation 7.661 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Blood Urea Nitrogen | Baseline | 30.37 mg/dL | Standard Deviation 8.092 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Blood Urea Nitrogen | Day 3/0Hr | 25.60 mg/dL | Standard Deviation 7.942 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Blood Urea Nitrogen | Day 2/)0Hr | 27.53 mg/dL | Standard Deviation 7.602 |
Secondary
Percentage of Participants With Normal S-K Levels at End of Study Day 2
Percentage (%) of subjects who achieve S-K normalization at end of Study Day 2
Time frame: 48 hours post first study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Combined All Three Cohorts) | Percentage of Participants With Normal S-K Levels at End of Study Day 2 | 90 percentage of participants |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Percentage of Participants With Normal S-K Levels at End of Study Day 2 | 75 percentage of participants |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Percentage of Participants With Normal S-K Levels at End of Study Day 2 | 95.8 percentage of participants |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Percentage of Participants With Normal S-K Levels at End of Study Day 2 | 100 percentage of participants |
Secondary
Serum Bicarbonate (HCO3) Levels
Serum bicarbonate compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 & 48 hours post dose on Study Days 2 and 3).
Time frame: 24 and 48 hours post study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Serum Bicarbonate (HCO3) Levels | Day 3/0 hr | 29.0 mmol/L | Standard Deviation 3.66 |
| Placebo (Combined All Three Cohorts) | Serum Bicarbonate (HCO3) Levels | Day 2/0 hr | 28.6 mmol/L | Standard Deviation 2.46 |
| Placebo (Combined All Three Cohorts) | Serum Bicarbonate (HCO3) Levels | Baseline | 28.1 mmol/L | Standard Deviation 2.99 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Bicarbonate (HCO3) Levels | Day 3/0 hr | 28.3 mmol/L | Standard Deviation 2.96 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Bicarbonate (HCO3) Levels | Day 2/0 hr | 29.2 mmol/L | Standard Deviation 3.51 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Bicarbonate (HCO3) Levels | Baseline | 28.6 mmol/L | Standard Deviation 3.11 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Bicarbonate (HCO3) Levels | Baseline | 28.1 mmol/L | Standard Deviation 3.26 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Bicarbonate (HCO3) Levels | Day 2/0 hr | 28.3 mmol/L | Standard Deviation 3.15 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Bicarbonate (HCO3) Levels | Day 3/0 hr | 28.7 mmol/L | Standard Deviation 3.25 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Bicarbonate (HCO3) Levels | Day 3/0 hr | 30.1 mmol/L | Standard Deviation 2.31 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Bicarbonate (HCO3) Levels | Day 2/0 hr | 30.1 mmol/L | Standard Deviation 1.79 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Bicarbonate (HCO3) Levels | Baseline | 27.4 mmol/L | Standard Deviation 3.58 |
Secondary
Serum Calcium (S-Ca) Levels
Serum calcium compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 & 48 hours post dose on Study Days 2 and 3).
Time frame: 24 and 48 hours post study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Serum Calcium (S-Ca) Levels | Baseline | 9.46 mg/dL | Standard Deviation 0.595 |
| Placebo (Combined All Three Cohorts) | Serum Calcium (S-Ca) Levels | Day 3/0 hr | 9.51 mg/dL | Standard Deviation 0.544 |
| Placebo (Combined All Three Cohorts) | Serum Calcium (S-Ca) Levels | Day 2/0 Hr | 9.39 mg/dL | Standard Deviation 0.439 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Calcium (S-Ca) Levels | Baseline | 9.37 mg/dL | Standard Deviation 0.341 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Calcium (S-Ca) Levels | Day 3/0 hr | 9.33 mg/dL | Standard Deviation 0.36 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Calcium (S-Ca) Levels | Day 2/0 Hr | 9.36 mg/dL | Standard Deviation 0.507 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Calcium (S-Ca) Levels | Day 2/0 Hr | 9.33 mg/dL | Standard Deviation 0.388 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Calcium (S-Ca) Levels | Baseline | 9.48 mg/dL | Standard Deviation 0.337 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Calcium (S-Ca) Levels | Day 3/0 hr | 9.30 mg/dL | Standard Deviation 0.397 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Calcium (S-Ca) Levels | Baseline | 9.50 mg/dL | Standard Deviation 0.469 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Calcium (S-Ca) Levels | Day 3/0 hr | 9.05 mg/dL | Standard Deviation 0.425 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Calcium (S-Ca) Levels | Day 2/0 Hr | 9.22 mg/dL | Standard Deviation 0.466 |
Secondary
Serum Magnesium (S-Mg) Levels
Serum magnesium compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 & 48 hours post dose on Study Days 2 and 3).
Time frame: 24 and 48 hours post study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Serum Magnesium (S-Mg) Levels | Baseline | 1.93 mg/dL | Standard Deviation 0.258 |
| Placebo (Combined All Three Cohorts) | Serum Magnesium (S-Mg) Levels | Day 3/0Hr | 1.90 mg/dL | Standard Deviation 0.204 |
| Placebo (Combined All Three Cohorts) | Serum Magnesium (S-Mg) Levels | Day 2/0Hr | 1.92 mg/dL | Standard Deviation 0.197 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Magnesium (S-Mg) Levels | Baseline | 1.95 mg/dL | Standard Deviation 0.327 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Magnesium (S-Mg) Levels | Day 3/0Hr | 1.89 mg/dL | Standard Deviation 0.257 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Magnesium (S-Mg) Levels | Day 2/0Hr | 1.93 mg/dL | Standard Deviation 0.271 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Magnesium (S-Mg) Levels | Day 2/0Hr | 1.94 mg/dL | Standard Deviation 0.182 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Magnesium (S-Mg) Levels | Baseline | 1.93 mg/dL | Standard Deviation 0.143 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Magnesium (S-Mg) Levels | Day 3/0Hr | 1.94 mg/dL | Standard Deviation 0.179 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Magnesium (S-Mg) Levels | Baseline | 1.85 mg/dL | Standard Deviation 0.235 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Magnesium (S-Mg) Levels | Day 3/0Hr | 1.83 mg/dL | Standard Deviation 0.218 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Magnesium (S-Mg) Levels | Day 2/0Hr | 1.81 mg/dL | Standard Deviation 0.225 |
Secondary
Serum Potassium (S-K) at Individual Time Points.
Serum potassium (S-K) at individual time points through Study day 3/0hour.
Time frame: First 48 hours of study
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 2nd Dose | 5.02 mmol/L | Standard Deviation 0.426 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 3rd Dose | 4.87 mmol/L | Standard Deviation 0.486 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 2/20Hr Post 1st Dose | 4.8 mmol/L | Standard Deviation 0.438 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 1/30 Min Post 1st Dose | 5.17 mmol/L | Standard Deviation 0.419 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 3/0Hr | 4.94 mmol/L | Standard Deviation 0.549 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 2nd Dose | 4.91 mmol/L | Standard Deviation 0.465 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Baseline | 5.14 mmol/L | Standard Deviation 0.358 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 3rd Dose | 4.82 mmol/L | Standard Deviation 0.558 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 1/2 Hour Post 1st Dose | 5.12 mmol/L | Standard Deviation 0.532 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 2/0Hr | 4.97 mmol/L | Standard Deviation 0.521 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 1st Dose | 4.97 mmol/L | Standard Deviation 0.564 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 1/1 Hour Post 1st Dose | 5.26 mmol/L | Standard Deviation 0.524 |
| Placebo (Combined All Three Cohorts) | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 1st Dose | 5.03 mmol/L | Standard Deviation 0.441 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/1 Hour Post 1st Dose | 5.23 mmol/L | Standard Deviation 0.535 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Baseline | 5.22 mmol/L | Standard Deviation 0.264 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/30 Min Post 1st Dose | 5.25 mmol/L | Standard Deviation 0.476 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 3rd Dose | 4.91 mmol/L | Standard Deviation 0.368 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 3rd Dose | 4.83 mmol/L | Standard Deviation 0.526 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/20Hr Post 1st Dose | 4.83 mmol/L | Standard Deviation 0.555 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 2nd Dose | 5.04 mmol/L | Standard Deviation 0.417 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 1st Dose | 4.97 mmol/L | Standard Deviation 0.363 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 3/0Hr | 4.92 mmol/L | Standard Deviation 0.506 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/0Hr | 4.90 mmol/L | Standard Deviation 0.447 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 2nd Dose | 5.14 mmol/L | Standard Deviation 0.609 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 1st Dose | 5.06 mmol/L | Standard Deviation 0.417 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/2 Hour Post 1st Dose | 5.35 mmol/L | Standard Deviation 0.505 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/30 Min Post 1st Dose | 5.09 mmol/L | Standard Deviation 0.624 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Baseline | 5.02 mmol/L | Standard Deviation 0.322 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 1st Dose | 4.93 mmol/L | Standard Deviation 0.518 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 2nd Dose | 4.80 mmol/L | Standard Deviation 0.543 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 3rd Dose | 4.68 mmol/L | Standard Deviation 0.577 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/0Hr | 4.66 mmol/L | Standard Deviation 0.434 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 1st Dose | 4.81 mmol/L | Standard Deviation 0.601 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 2nd Dose | 4.72 mmol/L | Standard Deviation 0.604 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 3rd Dose | 4.60 mmol/L | Standard Deviation 0.566 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 3/0Hr | 4.68 mmol/L | Standard Deviation 0.491 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/1 Hour Post 1st Dose | 5.03 mmol/L | Standard Deviation 0.565 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/2 Hour Post 1st Dose | 5.05 mmol/L | Standard Deviation 0.667 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/20Hr Post 1st Dose | 4.60 mmol/L | Standard Deviation 0.58 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 1st Dose | 4.53 mmol/L | Standard Deviation 0.411 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/30 Min Post 1st Dose | 5.03 mmol/L | Standard Deviation 0.456 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/0Hr | 4.73 mmol/L | Standard Deviation 0.463 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Baseline | 5.05 mmol/L | Standard Deviation 0.359 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/1 Hour Post 1st Dose | 4.94 mmol/L | Standard Deviation 0.438 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 3rd Dose | 4.50 mmol/L | Standard Deviation 0.397 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 2nd Dose | 4.68 mmol/L | Standard Deviation 0.42 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/20Hr Post 1st Dose | 4.19 mmol/L | Standard Deviation 0.378 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/2 Hour Post 1st Dose | 4.93 mmol/L | Standard Deviation 0.429 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 1/4Hr Post 1st Dose | 4.80 mmol/L | Standard Deviation 0.466 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 3/0Hr | 4.37 mmol/L | Standard Deviation 0.448 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 3rd Dose | 4.13 mmol/L | Standard Deviation 0.388 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Potassium (S-K) at Individual Time Points. | Day 2/4Hr Post 2nd Dose | 4.43 mmol/L | Standard Deviation 0.46 |
Secondary
Serum Sodium (S-Na) Levels
Serum sodium compared between the combined placebo-treated controls and the ZS-treated subjects (measured at 24 & 48 hours post dose on Study Days 2 and 3).
Time frame: 24 and 48 hours post study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Serum Sodium (S-Na) Levels | Baseline | 139.4 mmol/L | Standard Deviation 2.84 |
| Placebo (Combined All Three Cohorts) | Serum Sodium (S-Na) Levels | Day 3/0 hr | 140.0 mmol/L | Standard Deviation 3.36 |
| Placebo (Combined All Three Cohorts) | Serum Sodium (S-Na) Levels | Day 2/0 hr | 140.1 mmol/L | Standard Deviation 3.24 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Sodium (S-Na) Levels | Baseline | 139.1 mmol/L | Standard Deviation 3.65 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Sodium (S-Na) Levels | Day 3/0 hr | 138.5 mmol/L | Standard Deviation 2.28 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Serum Sodium (S-Na) Levels | Day 2/0 hr | 138.8 mmol/L | Standard Deviation 2.04 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Sodium (S-Na) Levels | Day 2/0 hr | 140.1 mmol/L | Standard Deviation 3.83 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Sodium (S-Na) Levels | Baseline | 140.0 mmol/L | Standard Deviation 3.09 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Serum Sodium (S-Na) Levels | Day 3/0 hr | 140.0 mmol/L | Standard Deviation 3.91 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Sodium (S-Na) Levels | Baseline | 137.7 mmol/L | Standard Deviation 3.45 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Sodium (S-Na) Levels | Day 3/0 hr | 139.6 mmol/L | Standard Deviation 3.5 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Serum Sodium (S-Na) Levels | Day 2/0 hr | 138.6 mmol/L | Standard Deviation 3.37 |
Secondary
Time Specific Decreases in S-K Levels of > = 0.5 mmol/L
Percentage of participants achieving a 0.5mmol/L drop from baseline at Study Days 2 and 3 at 0 hr.
Time frame: 24 and 48 hours post first study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Time Specific Decreases in S-K Levels of > = 0.5 mmol/L | Day 2/0Hr | 16.7 percentage of participants |
| Placebo (Combined All Three Cohorts) | Time Specific Decreases in S-K Levels of > = 0.5 mmol/L | Day 3/0Hr | 26.7 percentage of participants |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Time Specific Decreases in S-K Levels of > = 0.5 mmol/L | Day 3/0Hr | 41.7 percentage of participants |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Time Specific Decreases in S-K Levels of > = 0.5 mmol/L | Day 2/0Hr | 33.3 percentage of participants |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Time Specific Decreases in S-K Levels of > = 0.5 mmol/L | Day 2/0Hr | 37.5 percentage of participants |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Time Specific Decreases in S-K Levels of > = 0.5 mmol/L | Day 3/0Hr | 41.7 percentage of participants |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Time Specific Decreases in S-K Levels of > = 0.5 mmol/L | Day 2/0Hr | 33.3 percentage of participants |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Time Specific Decreases in S-K Levels of > = 0.5 mmol/L | Day 3/0Hr | 62.5 percentage of participants |
Secondary
Time Specific S-K Levels to Normalization
Percent of subjects achieving S-K normalization (\<=as defined by S-K levels of 3.5 to 4.9 mmol/L) from baseline at Study Days 2 and 3 at 0 hr.
Time frame: 48 and 72 hours post first study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Time Specific S-K Levels to Normalization | Day2/0Hr | 90 percentage of participants |
| Placebo (Combined All Three Cohorts) | Time Specific S-K Levels to Normalization | Day 3/0Hr | 90 percentage of participants |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Time Specific S-K Levels to Normalization | Day 3/0Hr | 100 percentage of participants |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Time Specific S-K Levels to Normalization | Day2/0Hr | 75 percentage of participants |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Time Specific S-K Levels to Normalization | Day2/0Hr | 95.8 percentage of participants |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Time Specific S-K Levels to Normalization | Day 3/0Hr | 95.8 percentage of participants |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Time Specific S-K Levels to Normalization | Day2/0Hr | 100 percentage of participants |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Time Specific S-K Levels to Normalization | Day 3/0Hr | 100 percentage of participants |
Secondary
Urea Nitrogen Excretion
Urea nitrogen excretion compared between the combined placebo-treated controls and the ZS-treated subjects (measured throughout two 24-hour periods on Study Days 1 and 2).
Time frame: 24 and 48 hours post study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Urea Nitrogen Excretion | Baseline | 525.0 mg/dL | Standard Deviation 219.79 |
| Placebo (Combined All Three Cohorts) | Urea Nitrogen Excretion | Day2/ 24-48 HR | 460.9 mg/dL | Standard Deviation 175.09 |
| Placebo (Combined All Three Cohorts) | Urea Nitrogen Excretion | Day1/ 0-24 HR | 389.2 mg/dL | Standard Deviation 179.91 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Urea Nitrogen Excretion | Baseline | 430.2 mg/dL | Standard Deviation 162.92 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Urea Nitrogen Excretion | Day2/ 24-48 HR | 337.6 mg/dL | Standard Deviation 115.06 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Urea Nitrogen Excretion | Day1/ 0-24 HR | 401.8 mg/dL | Standard Deviation 265.74 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Urea Nitrogen Excretion | Day1/ 0-24 HR | 414.1 mg/dL | Standard Deviation 177.54 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Urea Nitrogen Excretion | Baseline | 481.0 mg/dL | Standard Deviation 198.92 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Urea Nitrogen Excretion | Day2/ 24-48 HR | 477.0 mg/dL | Standard Deviation 157.04 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Urea Nitrogen Excretion | Baseline | 424.7 mg/dL | Standard Deviation 171.88 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Urea Nitrogen Excretion | Day2/ 24-48 HR | 416.6 mg/dL | Standard Deviation 219.56 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Urea Nitrogen Excretion | Day1/ 0-24 HR | 368.5 mg/dL | Standard Deviation 147.37 |
Secondary
Urine Potassium Excretion
Urine potassium excretion compared between the combined placebo-treated controls and the ZS-treated subjects (measured throughout two 24-hour periods on Study Days 1 and 2).
Time frame: 24 and 48 hours post study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Urine Potassium Excretion | Day2/24-48Hr | 29.2 mmol/L | Standard Deviation 6.42 |
| Placebo (Combined All Three Cohorts) | Urine Potassium Excretion | Day1/0-24Hr | 28.7 mmol/L | Standard Deviation 6.41 |
| Placebo (Combined All Three Cohorts) | Urine Potassium Excretion | Baseline | 36.6 mmol/L | Standard Deviation 12.47 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Urine Potassium Excretion | Day2/24-48Hr | 31.0 mmol/L | Standard Deviation 0 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Urine Potassium Excretion | Baseline | 32.2 mmol/L | Standard Deviation 2.12 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Urine Potassium Excretion | Day1/0-24Hr | 32.0 mmol/L | Standard Deviation 3.16 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Urine Potassium Excretion | Day1/0-24Hr | 30.6 mmol/L | Standard Deviation 5.96 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Urine Potassium Excretion | Baseline | 38.3 mmol/L | Standard Deviation 11.82 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Urine Potassium Excretion | Day2/24-48Hr | 30.5 mmol/L | Standard Deviation 6.51 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Urine Potassium Excretion | Day2/24-48Hr | 16.9 mmol/L | Standard Deviation 8.8 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Urine Potassium Excretion | Day1/0-24Hr | 19.7 mmol/L | Standard Deviation 9.69 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Urine Potassium Excretion | Baseline | 30.3 mmol/L | Standard Deviation 15.81 |
Secondary
Urine Sodium Excretion
Urine sodium excretion compared between the combined placebo-treated controls and the ZS-treated subjects (measured throughout two 24-hour periods on Study Days 1 and 2).
Time frame: 24 and 48 hours post first study drug dose
Population: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Combined All Three Cohorts) | Urine Sodium Excretion | Baseline | 91.5 mmol/L | Standard Deviation 30.31 |
| Placebo (Combined All Three Cohorts) | Urine Sodium Excretion | Day 2/24-48Hr | 80.1 mmol/L | Standard Deviation 28.21 |
| Placebo (Combined All Three Cohorts) | Urine Sodium Excretion | Day 1/0-24Hr | 74.4 mmol/L | Standard Deviation 24.8 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Urine Sodium Excretion | Baseline | 73.5 mmol/L | Standard Deviation 29.79 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Urine Sodium Excretion | Day 2/24-48Hr | 67.5 mmol/L | Standard Deviation 26.63 |
| Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily | Urine Sodium Excretion | Day 1/0-24Hr | 66.7 mmol/L | Standard Deviation 18.49 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Urine Sodium Excretion | Day 1/0-24Hr | 66.8 mmol/L | Standard Deviation 26.26 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Urine Sodium Excretion | Baseline | 81.7 mmol/L | Standard Deviation 33.16 |
| Sodium Zirconium Cyclosilicate 3 g Three Times Daily | Urine Sodium Excretion | Day 2/24-48Hr | 71.6 mmol/L | Standard Deviation 31.61 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Urine Sodium Excretion | Baseline | 74.5 mmol/L | Standard Deviation 34.2 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Urine Sodium Excretion | Day 2/24-48Hr | 75.8 mmol/L | Standard Deviation 35.74 |
| Sodium Zirconium Cyclosilicate 10 g Three Times Daily | Urine Sodium Excretion | Day 1/0-24Hr | 67.1 mmol/L | Standard Deviation 29.19 |