Trial Outcomes & Findings for Safety & Efficacy of Zirconium Silicate in Chronic Kidney Disease or Moderate Kidney Dysfunction With Mild Hyperkalemia (NCT NCT01493024)
NCT ID: NCT01493024
Last Updated: 2018-06-29
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
90 participants
Primary outcome timeframe
24 and 48 hours post first study drug dose
Results posted on
2018-06-29
Participant Flow
Participants took part in the study at 9 centers in the United States from 28 November 2011 to 22 May 2012.
Combined Placebo Group
Participant milestones
| Measure |
Placebo
Placebo randomized to mimic escalating doses of experimental drug administered three times daily .
|
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
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
30
|
12
|
24
|
24
|
|
Overall Study
COMPLETED
|
30
|
12
|
24
|
24
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Intent-To-Treat Population
Baseline characteristics by cohort
| Measure |
Placebo
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times daily .
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
Total
n=90 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
69.7 Years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
70.3 Years
STANDARD_DEVIATION 6.9 • n=7 Participants
|
72.0 Years
STANDARD_DEVIATION 6.3 • n=5 Participants
|
72.3 Years
STANDARD_DEVIATION 11.7 • n=4 Participants
|
71.1 Years
STANDARD_DEVIATION 9.59 • n=21 Participants
|
|
Sex/Gender, Customized
Female
|
7 Participants
n=5 Participants • Intent-To-Treat Population
|
6 Participants
n=7 Participants • Intent-To-Treat Population
|
10 Participants
n=5 Participants • Intent-To-Treat Population
|
15 Participants
n=4 Participants • Intent-To-Treat Population
|
38 Participants
n=21 Participants • Intent-To-Treat Population
|
|
Sex/Gender, Customized
Male
|
23 Participants
n=5 Participants • Intent-To-Treat Population
|
6 Participants
n=7 Participants • Intent-To-Treat Population
|
14 Participants
n=5 Participants • Intent-To-Treat Population
|
9 Participants
n=4 Participants • Intent-To-Treat Population
|
52 Participants
n=21 Participants • Intent-To-Treat Population
|
|
Race/Ethnicity, Customized
White
|
29 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
88 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Serum potassium
|
5.19 mmol/L
STANDARD_DEVIATION 0.301 • n=5 Participants
|
5.25 mmol/L
STANDARD_DEVIATION 0.144 • n=7 Participants
|
5.11 mmol/L
STANDARD_DEVIATION 0.328 • n=5 Participants
|
5.13 mmol/L
STANDARD_DEVIATION 0.378 • n=4 Participants
|
5.16 mmol/L
STANDARD_DEVIATION 0.314 • n=21 Participants
|
|
Weight at baseline
|
95.15 kilograms
STANDARD_DEVIATION 22.122 • n=5 Participants
|
84.76 kilograms
STANDARD_DEVIATION 18.022 • n=7 Participants
|
88.96 kilograms
STANDARD_DEVIATION 22.002 • n=5 Participants
|
86.59 kilograms
STANDARD_DEVIATION 26.311 • n=4 Participants
|
89.83 kilograms
STANDARD_DEVIATION 22.794 • n=21 Participants
|
|
GFR at Study Day 0
|
45.6 mL/min/1.73 m^2
STANDARD_DEVIATION 9.05 • n=5 Participants
|
46.2 mL/min/1.73 m^2
STANDARD_DEVIATION 4.99 • n=7 Participants
|
46.8 mL/min/1.73 m^2
STANDARD_DEVIATION 7.14 • n=5 Participants
|
43.5 mL/min/1.73 m^2
STANDARD_DEVIATION 9.01 • n=4 Participants
|
45.4 mL/min/1.73 m^2
STANDARD_DEVIATION 8.09 • n=21 Participants
|
PRIMARY outcome
Timeframe: 24 and 48 hours post first study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
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)
Standard Error NA
A consequence of the modeling estimate when control is the reference standard
|
-0.00035 log(mmol/L/hour)
Standard Error 0.001166
|
-0.00169 log(mmol/L/hour)
Standard Error 0.000932
|
-0.000143 log(mmol/L/hour)
Standard Error 0.000932
|
|
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)
Standard Error NA
A consequence of the modeling estimate when control is the reference standard
|
-0.00045 log(mmol/L/hour)
Standard Error 0.000555
|
-0.00089 log(mmol/L/hour)
Standard Error 0.000444
|
-0.00256 log(mmol/L/hour)
Standard Error 0.000444
|
SECONDARY outcome
Timeframe: First 48 hours of studyPopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Serum potassium (S-K) at individual time points through Study day 3/0hour.
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Serum Potassium (S-K) at Individual Time Points.
Baseline
|
5.14 mmol/L
Standard Deviation 0.358
|
5.22 mmol/L
Standard Deviation 0.264
|
5.02 mmol/L
Standard Deviation 0.322
|
5.05 mmol/L
Standard Deviation 0.359
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 1/4Hr Post 1st Dose
|
4.97 mmol/L
Standard Deviation 0.564
|
5.06 mmol/L
Standard Deviation 0.417
|
4.93 mmol/L
Standard Deviation 0.518
|
4.80 mmol/L
Standard Deviation 0.466
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 1/4Hr Post 2nd Dose
|
4.91 mmol/L
Standard Deviation 0.465
|
5.14 mmol/L
Standard Deviation 0.609
|
4.80 mmol/L
Standard Deviation 0.543
|
4.68 mmol/L
Standard Deviation 0.420
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 1/4Hr Post 3rd Dose
|
4.82 mmol/L
Standard Deviation 0.558
|
4.91 mmol/L
Standard Deviation 0.368
|
4.68 mmol/L
Standard Deviation 0.577
|
4.50 mmol/L
Standard Deviation 0.397
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 2/0Hr
|
4.97 mmol/L
Standard Deviation 0.521
|
4.90 mmol/L
Standard Deviation 0.447
|
4.66 mmol/L
Standard Deviation 0.434
|
4.73 mmol/L
Standard Deviation 0.463
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 2/4Hr Post 1st Dose
|
5.03 mmol/L
Standard Deviation 0.441
|
4.97 mmol/L
Standard Deviation 0.363
|
4.81 mmol/L
Standard Deviation 0.601
|
4.53 mmol/L
Standard Deviation 0.411
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 2/4Hr Post 2nd Dose
|
5.02 mmol/L
Standard Deviation 0.426
|
5.04 mmol/L
Standard Deviation 0.417
|
4.72 mmol/L
Standard Deviation 0.604
|
4.43 mmol/L
Standard Deviation 0.460
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 2/4Hr Post 3rd Dose
|
4.87 mmol/L
Standard Deviation 0.486
|
4.83 mmol/L
Standard Deviation 0.526
|
4.60 mmol/L
Standard Deviation 0.566
|
4.13 mmol/L
Standard Deviation 0.388
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 3/0Hr
|
4.94 mmol/L
Standard Deviation 0.549
|
4.92 mmol/L
Standard Deviation 0.506
|
4.68 mmol/L
Standard Deviation 0.491
|
4.37 mmol/L
Standard Deviation 0.448
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 1/30 Min Post 1st Dose
|
5.17 mmol/L
Standard Deviation 0.419
|
5.25 mmol/L
Standard Deviation 0.476
|
5.09 mmol/L
Standard Deviation 0.624
|
5.03 mmol/L
Standard Deviation 0.456
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 1/1 Hour Post 1st Dose
|
5.26 mmol/L
Standard Deviation 0.524
|
5.23 mmol/L
Standard Deviation 0.535
|
5.03 mmol/L
Standard Deviation 0.565
|
4.94 mmol/L
Standard Deviation 0.438
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 1/2 Hour Post 1st Dose
|
5.12 mmol/L
Standard Deviation 0.532
|
5.35 mmol/L
Standard Deviation 0.505
|
5.05 mmol/L
Standard Deviation 0.667
|
4.93 mmol/L
Standard Deviation 0.429
|
|
Serum Potassium (S-K) at Individual Time Points.
Day 2/20Hr Post 1st Dose
|
4.8 mmol/L
Standard Deviation 0.438
|
4.83 mmol/L
Standard Deviation 0.555
|
4.60 mmol/L
Standard Deviation 0.580
|
4.19 mmol/L
Standard Deviation 0.378
|
SECONDARY outcome
Timeframe: 48 and 72 hours post first study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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.
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Time Specific S-K Levels to Normalization
Day2/0Hr
|
90 percentage of participants
|
75 percentage of participants
|
95.8 percentage of participants
|
100 percentage of participants
|
|
Time Specific S-K Levels to Normalization
Day 3/0Hr
|
90 percentage of participants
|
100 percentage of participants
|
95.8 percentage of participants
|
100 percentage of participants
|
SECONDARY outcome
Timeframe: 24 and 48 hours post first study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Percentage of participants achieving a 0.5mmol/L drop from baseline at Study Days 2 and 3 at 0 hr.
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Time Specific Decreases in S-K Levels of > = 0.5 mmol/L
Day 2/0Hr
|
16.7 percentage of participants
|
33.3 percentage of participants
|
37.5 percentage of participants
|
33.3 percentage of participants
|
|
Time Specific Decreases in S-K Levels of > = 0.5 mmol/L
Day 3/0Hr
|
26.7 percentage of participants
|
41.7 percentage of participants
|
41.7 percentage of participants
|
62.5 percentage of participants
|
SECONDARY outcome
Timeframe: 48 hours post first study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Percentage (%) of subjects who achieve S-K normalization at end of Study Day 2
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Percentage of Participants With Normal S-K Levels at End of Study Day 2
|
90 percentage of participants
|
75 percentage of participants
|
95.8 percentage of participants
|
100 percentage of participants
|
SECONDARY outcome
Timeframe: 24 and 48 hours post first study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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).
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Urine Sodium Excretion
Day 2/24-48Hr
|
80.1 mmol/L
Standard Deviation 28.21
|
67.5 mmol/L
Standard Deviation 26.63
|
71.6 mmol/L
Standard Deviation 31.61
|
75.8 mmol/L
Standard Deviation 35.74
|
|
Urine Sodium Excretion
Baseline
|
91.5 mmol/L
Standard Deviation 30.31
|
73.5 mmol/L
Standard Deviation 29.79
|
81.7 mmol/L
Standard Deviation 33.16
|
74.5 mmol/L
Standard Deviation 34.20
|
|
Urine Sodium Excretion
Day 1/0-24Hr
|
74.4 mmol/L
Standard Deviation 24.8
|
66.7 mmol/L
Standard Deviation 18.49
|
66.8 mmol/L
Standard Deviation 26.26
|
67.1 mmol/L
Standard Deviation 29.19
|
SECONDARY outcome
Timeframe: 24 and 48 hours post study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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).
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Urine Potassium Excretion
Baseline
|
36.6 mmol/L
Standard Deviation 12.47
|
32.2 mmol/L
Standard Deviation 2.12
|
38.3 mmol/L
Standard Deviation 11.82
|
30.3 mmol/L
Standard Deviation 15.81
|
|
Urine Potassium Excretion
Day1/0-24Hr
|
28.7 mmol/L
Standard Deviation 6.41
|
32.0 mmol/L
Standard Deviation 3.16
|
30.6 mmol/L
Standard Deviation 5.96
|
19.7 mmol/L
Standard Deviation 9.69
|
|
Urine Potassium Excretion
Day2/24-48Hr
|
29.2 mmol/L
Standard Deviation 6.42
|
31.0 mmol/L
Standard Deviation 0.00
|
30.5 mmol/L
Standard Deviation 6.51
|
16.9 mmol/L
Standard Deviation 8.80
|
SECONDARY outcome
Timeframe: 24 and 48 hours post study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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).
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Urea Nitrogen Excretion
Baseline
|
525.0 mg/dL
Standard Deviation 219.79
|
430.2 mg/dL
Standard Deviation 162.92
|
481.0 mg/dL
Standard Deviation 198.92
|
424.7 mg/dL
Standard Deviation 171.88
|
|
Urea Nitrogen Excretion
Day1/ 0-24 HR
|
389.2 mg/dL
Standard Deviation 179.91
|
401.8 mg/dL
Standard Deviation 265.74
|
414.1 mg/dL
Standard Deviation 177.54
|
368.5 mg/dL
Standard Deviation 147.37
|
|
Urea Nitrogen Excretion
Day2/ 24-48 HR
|
460.9 mg/dL
Standard Deviation 175.09
|
337.6 mg/dL
Standard Deviation 115.06
|
477.0 mg/dL
Standard Deviation 157.04
|
416.6 mg/dL
Standard Deviation 219.56
|
SECONDARY outcome
Timeframe: 24 and 48 hours post study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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).
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Blood Urea Nitrogen
Baseline
|
24.50 mg/dL
Standard Deviation 7.481
|
23.52 mg/dL
Standard Deviation 8.217
|
25.16 mg/dL
Standard Deviation 8.065
|
30.37 mg/dL
Standard Deviation 8.092
|
|
Blood Urea Nitrogen
Day 2/)0Hr
|
24.05 mg/dL
Standard Deviation 7.626
|
23.63 mg/dL
Standard Deviation 7.241
|
23.98 mg/dL
Standard Deviation 7.619
|
27.53 mg/dL
Standard Deviation 7.602
|
|
Blood Urea Nitrogen
Day 3/0Hr
|
24.50 mg/dL
Standard Deviation 7.284
|
23.33 mg/dL
Standard Deviation 7.895
|
24.04 mg/dL
Standard Deviation 7.661
|
25.60 mg/dL
Standard Deviation 7.942
|
SECONDARY outcome
Timeframe: 24 and 48 hours post study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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).
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Serum Magnesium (S-Mg) Levels
Baseline
|
1.93 mg/dL
Standard Deviation 0.258
|
1.95 mg/dL
Standard Deviation 0.327
|
1.93 mg/dL
Standard Deviation 0.143
|
1.85 mg/dL
Standard Deviation 0.235
|
|
Serum Magnesium (S-Mg) Levels
Day 2/0Hr
|
1.92 mg/dL
Standard Deviation 0.197
|
1.93 mg/dL
Standard Deviation 0.271
|
1.94 mg/dL
Standard Deviation 0.182
|
1.81 mg/dL
Standard Deviation 0.225
|
|
Serum Magnesium (S-Mg) Levels
Day 3/0Hr
|
1.90 mg/dL
Standard Deviation 0.204
|
1.89 mg/dL
Standard Deviation 0.257
|
1.94 mg/dL
Standard Deviation 0.179
|
1.83 mg/dL
Standard Deviation 0.218
|
SECONDARY outcome
Timeframe: 24 and 48 hours post study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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).
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Serum Calcium (S-Ca) Levels
Baseline
|
9.46 mg/dL
Standard Deviation 0.595
|
9.37 mg/dL
Standard Deviation 0.341
|
9.48 mg/dL
Standard Deviation 0.337
|
9.50 mg/dL
Standard Deviation 0.469
|
|
Serum Calcium (S-Ca) Levels
Day 2/0 Hr
|
9.39 mg/dL
Standard Deviation 0.439
|
9.36 mg/dL
Standard Deviation 0.507
|
9.33 mg/dL
Standard Deviation 0.388
|
9.22 mg/dL
Standard Deviation 0.466
|
|
Serum Calcium (S-Ca) Levels
Day 3/0 hr
|
9.51 mg/dL
Standard Deviation 0.544
|
9.33 mg/dL
Standard Deviation 0.360
|
9.30 mg/dL
Standard Deviation 0.397
|
9.05 mg/dL
Standard Deviation 0.425
|
SECONDARY outcome
Timeframe: 24 and 48 hours post study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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).
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Serum Sodium (S-Na) Levels
Baseline
|
139.4 mmol/L
Standard Deviation 2.84
|
139.1 mmol/L
Standard Deviation 3.65
|
140.0 mmol/L
Standard Deviation 3.09
|
137.7 mmol/L
Standard Deviation 3.45
|
|
Serum Sodium (S-Na) Levels
Day 2/0 hr
|
140.1 mmol/L
Standard Deviation 3.24
|
138.8 mmol/L
Standard Deviation 2.04
|
140.1 mmol/L
Standard Deviation 3.83
|
138.6 mmol/L
Standard Deviation 3.37
|
|
Serum Sodium (S-Na) Levels
Day 3/0 hr
|
140.0 mmol/L
Standard Deviation 3.36
|
138.5 mmol/L
Standard Deviation 2.28
|
140.0 mmol/L
Standard Deviation 3.91
|
139.6 mmol/L
Standard Deviation 3.50
|
SECONDARY outcome
Timeframe: 24 and 48 hours post study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
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).
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Serum Bicarbonate (HCO3) Levels
Baseline
|
28.1 mmol/L
Standard Deviation 2.99
|
28.6 mmol/L
Standard Deviation 3.11
|
28.1 mmol/L
Standard Deviation 3.26
|
27.4 mmol/L
Standard Deviation 3.58
|
|
Serum Bicarbonate (HCO3) Levels
Day 2/0 hr
|
28.6 mmol/L
Standard Deviation 2.46
|
29.2 mmol/L
Standard Deviation 3.51
|
28.3 mmol/L
Standard Deviation 3.15
|
30.1 mmol/L
Standard Deviation 1.79
|
|
Serum Bicarbonate (HCO3) Levels
Day 3/0 hr
|
29.0 mmol/L
Standard Deviation 3.66
|
28.3 mmol/L
Standard Deviation 2.96
|
28.7 mmol/L
Standard Deviation 3.25
|
30.1 mmol/L
Standard Deviation 2.31
|
SECONDARY outcome
Timeframe: 24 and 48 hours post study drug dosePopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
24-hour urinary excretion of potassium on Study Days 1 and Day 2
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
24-hour Urinary Excretion of Potassium
Baseline
|
56.5 mmol/24 hour
Standard Deviation 33.96
|
62.4 mmol/24 hour
Standard Deviation 31.51
|
58.9 mmol/24 hour
Standard Deviation 20.44
|
46.9 mmol/24 hour
Standard Deviation 23.67
|
|
24-hour Urinary Excretion of Potassium
Study Day 1
|
64.7 mmol/24 hour
Standard Deviation 28.02
|
89.4 mmol/24 hour
Standard Deviation 46.62
|
60.5 mmol/24 hour
Standard Deviation 25.42
|
41.0 mmol/24 hour
Standard Deviation 20.49
|
|
24-hour Urinary Excretion of Potassium
Study Day 2
|
65.4 mmol/24 hour
Standard Deviation 29.23
|
86.6 mmol/24 hour
Standard Deviation 52.64
|
58.1 mmol/24 hour
Standard Deviation 24.77
|
31.1 mmol/24 hour
Standard Deviation 16.55
|
SECONDARY outcome
Timeframe: 48 hoursPopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
24-hour urinary excretion of sodium on Study Days 1 and Day 2
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
24-hour Urinary Excretion of Sodium
Baseline
|
145 mmol/24 hour
Standard Deviation 93.05
|
132.8 mmol/24 hour
Standard Deviation 51.09
|
124.0 mmol/24 hour
Standard Deviation 46.24
|
114.8 mmol/24 hour
Standard Deviation 49.0
|
|
24-hour Urinary Excretion of Sodium
Study Day 1
|
169.4 mmol/24 hour
Standard Deviation 88.90
|
173.7 mmol/24 hour
Standard Deviation 64.02
|
136.6 mmol/24 hour
Standard Deviation 79.5
|
141.0 mmol/24 hour
Standard Deviation 68.05
|
|
24-hour Urinary Excretion of Sodium
Study Day 2
|
181.8 mmol/24 hour
Standard Deviation 101.42
|
181.5 mmol/24 hour
Standard Deviation 101.63
|
132.5 mmol/24 hour
Standard Deviation 63.06
|
140.2 mmol/24 hour
Standard Deviation 66.86
|
SECONDARY outcome
Timeframe: 48 hoursPopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
24-hour urinary excretion of urea nitrogen on Study Days 1 and Day 2
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
24-hour Urinary Excretion of Urea Nitrogen
Baseline
|
7.66 g/24 hour
Standard Deviation 3.622
|
7.59 g/24 hour
Standard Deviation 2.768
|
7.03 g/24 hour
Standard Deviation 2.679
|
6.74 g/24 hour
Standard Deviation 2.618
|
|
24-hour Urinary Excretion of Urea Nitrogen
Day 1
|
8.30 g/24 hour
Standard Deviation 3.832
|
8.51 g/24 hour
Standard Deviation 5.549
|
7.99 g/24 hour
Standard Deviation 3.929
|
7.80 g/24 hour
Standard Deviation 3.460
|
|
24-hour Urinary Excretion of Urea Nitrogen
Day 2
|
10.37 g/24 hour
Standard Deviation 6.585
|
8.68 g/24 hour
Standard Deviation 2.475
|
8.57 g/24 hour
Standard Deviation 3.453
|
7.49 g/24 hour
Standard Deviation 3.077
|
SECONDARY outcome
Timeframe: 48 hoursPopulation: Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
24-hour urinary excretion of creatinine on Study Days 1 and Day 2
Outcome measures
| Measure |
Placebo (Combined All Three Cohorts)
n=30 Participants
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 Participants
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 Participants
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
24-hour Urinary Excretion of Creatinine
Baseline
|
1175.39 mg/24 hour
Standard Deviation 482.708
|
1149.00 mg/24 hour
Standard Deviation 483.740
|
1126.26 mg/24 hour
Standard Deviation 446.745
|
1015.67 mg/24 hour
Standard Deviation 471.275
|
|
24-hour Urinary Excretion of Creatinine
Day 1
|
1157.12 mg/24 hour
Standard Deviation 506.515
|
1027.50 mg/24 hour
Standard Deviation 301.315
|
996.45 mg/24 hour
Standard Deviation 442.333
|
1008.25 mg/24 hour
Standard Deviation 428.524
|
|
24-hour Urinary Excretion of Creatinine
Day 2
|
1270.71 mg/24 hour
Standard Deviation 544.596
|
1092.23 mg/24 hour
Standard Deviation 411.469
|
1050.29 mg/24 hour
Standard Deviation 344.882
|
1028.79 mg/24 hour
Standard Deviation 430.408
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=30 participants at risk
Placebo randomized to mimic escalating doses of experimental drug administered three times daily .
|
Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily
n=12 participants at risk
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 3 g Three Times Daily
n=24 participants at risk
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
|
Sodium Zirconium Cyclosilicate 10 g Three Times Daily
n=24 participants at risk
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
|
|---|---|---|---|---|
|
Vascular disorders
Hypertension
|
0.00%
0/30 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
4.2%
1/24 • Number of events 1 • Study Days 1 to 7
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/30 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
4.2%
1/24 • Number of events 1 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/30 • Study Days 1 to 7
|
8.3%
1/12 • Number of events 1 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
4.2%
1/24 • Number of events 1 • Study Days 1 to 7
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/30 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
4.2%
1/24 • Number of events 1 • Study Days 1 to 7
|
|
Gastrointestinal disorders
Nausea
|
3.3%
1/30 • Number of events 1 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
4.2%
1/24 • Number of events 1 • Study Days 1 to 7
|
8.3%
2/24 • Number of events 2 • Study Days 1 to 7
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
1/30 • Number of events 1 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
12.5%
3/24 • Number of events 3 • Study Days 1 to 7
|
|
Investigations
Aspartate aminotransferae increased
|
0.00%
0/30 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
4.2%
1/24 • Number of events 1 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/30 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
4.2%
1/24 • Number of events 1 • Study Days 1 to 7
|
|
Gastrointestinal disorders
Abdominal tenderness
|
3.3%
1/30 • Number of events 2 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/30 • Study Days 1 to 7
|
8.3%
1/12 • Number of events 2 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/30 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
4.2%
1/24 • Number of events 1 • Study Days 1 to 7
|
8.3%
2/24 • Number of events 2 • Study Days 1 to 7
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/30 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
4.2%
1/24 • Number of events 1 • Study Days 1 to 7
|
|
Nervous system disorders
Headache
|
3.3%
1/30 • Number of events 1 • Study Days 1 to 7
|
0.00%
0/12 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
0.00%
0/24 • Study Days 1 to 7
|
Additional Information
AstraZeneca Clinical Study Information Center
ZS Pharma, Inc
Phone: 1-877-240-9479
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee ZS Pharma has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER