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Safety & Efficacy of Zirconium Silicate in Chronic Kidney Disease or Moderate Kidney Dysfunction With Mild Hyperkalemia

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ClinicalTrials.gov Identifier: NCT01493024
Recruitment Status : Completed
First Posted : December 15, 2011
Results First Posted : June 29, 2018
Last Update Posted : June 29, 2018
Sponsor:
Information provided by (Responsible Party):
ZS Pharma, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Supportive Care
Conditions Hyperkalemia
Chronic Kidney Disease
Kidney Dysfunction
Interventions Drug: Zirconium silicate (ZS)
Drug: Placebo
Enrollment 90
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
Arm/Group Title 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
Hide Arm/Group Description Placebo randomized to mimic escalating doses of experimental drug administered 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, orally as a suspension in water Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Period Title: Overall Study
Started 30 12 24 24
Completed 30 12 24 24
Not Completed 0 0 0 0
Arm/Group Title 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
Hide Arm/Group Description Placebo randomized to mimic escalating doses of experimental drug administered 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, orally as a suspension in water Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water Total of all reporting groups
Overall Number of Baseline Participants 30 12 24 24 90
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 12 participants 24 participants 24 participants 90 participants
69.7  (11.0) 70.3  (6.9) 72.0  (6.3) 72.3  (11.7) 71.1  (9.59)
Sex/Gender, Customized   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 12 participants 24 participants 24 participants 90 participants
Female
7
  23.3%
6
  50.0%
10
  41.7%
15
  62.5%
38
  42.2%
Male
23
  76.7%
6
  50.0%
14
  58.3%
9
  37.5%
52
  57.8%
[1]
Measure Description: Patients' gender (Female / Male)
[2]
Measure Analysis Population Description: Intent-To-Treat Population
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 12 participants 24 participants 24 participants 90 participants
White
29
  96.7%
12
 100.0%
24
 100.0%
23
  95.8%
88
  97.8%
Black or African American
1
   3.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.1%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.2%
1
   1.1%
Serum potassium   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 30 participants 12 participants 24 participants 24 participants 90 participants
5.19  (0.301) 5.25  (0.144) 5.11  (0.328) 5.13  (0.378) 5.16  (0.314)
[1]
Measure Description: Mean of the screening time points (0 hour, 30 minutes, and 1 hour) determined by the central laboratory
Weight at baseline  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 30 participants 12 participants 24 participants 24 participants 90 participants
95.15  (22.122) 84.76  (18.022) 88.96  (22.002) 86.59  (26.311) 89.83  (22.794)
GFR at Study Day 0  
Mean (Standard Deviation)
Unit of measure:  mL/min/1.73 m^2
Number Analyzed 30 participants 12 participants 24 participants 24 participants 90 participants
45.6  (9.05) 46.2  (4.99) 46.8  (7.14) 43.5  (9.01) 45.4  (8.09)
1.Primary Outcome
Title Difference in the Exponential Rate of Change in Serum Potassium (S-K) Levels Versus Placebo During the Initial 48 Hours of Study Drug Treatment
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Error)
Unit of Measure: log(mmol/L/hour)
Day2/0 Hr ( 24 hours) 0 [1]   (NA) -0.00035  (0.001166) -0.00169  (0.000932) -0.000143  (0.000932)
Day 3/0 Hr (48 hours) 0 [1]   (NA) -0.00045  (0.000555) -0.00089  (0.000444) -0.00256  (0.000444)
[1]
A consequence of the modeling estimate when control is the reference standard
2.Secondary Outcome
Title Serum Potassium (S-K) at Individual Time Points.
Hide Description Serum potassium (S-K) at individual time points through Study day 3/0hour.
Time Frame First 48 hours of study
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mmol/L
Baseline 5.14  (0.358) 5.22  (0.264) 5.02  (0.322) 5.05  (0.359)
Day 1/4Hr Post 1st Dose 4.97  (0.564) 5.06  (0.417) 4.93  (0.518) 4.80  (0.466)
Day 1/4Hr Post 2nd Dose 4.91  (0.465) 5.14  (0.609) 4.80  (0.543) 4.68  (0.420)
Day 1/4Hr Post 3rd Dose 4.82  (0.558) 4.91  (0.368) 4.68  (0.577) 4.50  (0.397)
Day 2/0Hr 4.97  (0.521) 4.90  (0.447) 4.66  (0.434) 4.73  (0.463)
Day 2/4Hr Post 1st Dose 5.03  (0.441) 4.97  (0.363) 4.81  (0.601) 4.53  (0.411)
Day 2/4Hr Post 2nd Dose 5.02  (0.426) 5.04  (0.417) 4.72  (0.604) 4.43  (0.460)
Day 2/4Hr Post 3rd Dose 4.87  (0.486) 4.83  (0.526) 4.60  (0.566) 4.13  (0.388)
Day 3/0Hr 4.94  (0.549) 4.92  (0.506) 4.68  (0.491) 4.37  (0.448)
Day 1/30 Min Post 1st Dose 5.17  (0.419) 5.25  (0.476) 5.09  (0.624) 5.03  (0.456)
Day 1/1 Hour Post 1st Dose 5.26  (0.524) 5.23  (0.535) 5.03  (0.565) 4.94  (0.438)
Day 1/2 Hour Post 1st Dose 5.12  (0.532) 5.35  (0.505) 5.05  (0.667) 4.93  (0.429)
Day 2/20Hr Post 1st Dose 4.8  (0.438) 4.83  (0.555) 4.60  (0.580) 4.19  (0.378)
3.Secondary Outcome
Title Time Specific S-K Levels to Normalization
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Measure Type: Number
Unit of Measure: percentage of participants
Day2/0Hr 90 75 95.8 100
Day 3/0Hr 90 100 95.8 100
4.Secondary Outcome
Title Time Specific Decreases in S-K Levels of > = 0.5 mmol/L
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Measure Type: Number
Unit of Measure: percentage of participants
Day 2/0Hr 16.7 33.3 37.5 33.3
Day 3/0Hr 26.7 41.7 41.7 62.5
5.Secondary Outcome
Title Percentage of Participants With Normal S-K Levels at End of Study Day 2
Hide Description Percentage (%) of subjects who achieve S-K normalization at end of Study Day 2
Time Frame 48 hours post first study drug dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Measure Type: Number
Unit of Measure: percentage of participants
90 75 95.8 100
6.Secondary Outcome
Title Urine Sodium Excretion
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mmol/L
Baseline 91.5  (30.31) 73.5  (29.79) 81.7  (33.16) 74.5  (34.20)
Day 1/0-24Hr 74.4  (24.8) 66.7  (18.49) 66.8  (26.26) 67.1  (29.19)
Day 2/24-48Hr 80.1  (28.21) 67.5  (26.63) 71.6  (31.61) 75.8  (35.74)
7.Secondary Outcome
Title Urine Potassium Excretion
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mmol/L
Baseline 36.6  (12.47) 32.2  (2.12) 38.3  (11.82) 30.3  (15.81)
Day1/0-24Hr 28.7  (6.41) 32.0  (3.16) 30.6  (5.96) 19.7  (9.69)
Day2/24-48Hr 29.2  (6.42) 31.0  (0.00) 30.5  (6.51) 16.9  (8.80)
8.Secondary Outcome
Title Urea Nitrogen Excretion
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 525.0  (219.79) 430.2  (162.92) 481.0  (198.92) 424.7  (171.88)
Day1/ 0-24 HR 389.2  (179.91) 401.8  (265.74) 414.1  (177.54) 368.5  (147.37)
Day2/ 24-48 HR 460.9  (175.09) 337.6  (115.06) 477.0  (157.04) 416.6  (219.56)
9.Secondary Outcome
Title Blood Urea Nitrogen
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 24.50  (7.481) 23.52  (8.217) 25.16  (8.065) 30.37  (8.092)
Day 2/)0Hr 24.05  (7.626) 23.63  (7.241) 23.98  (7.619) 27.53  (7.602)
Day 3/0Hr 24.50  (7.284) 23.33  (7.895) 24.04  (7.661) 25.60  (7.942)
10.Secondary Outcome
Title Serum Magnesium (S-Mg) Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 1.93  (0.258) 1.95  (0.327) 1.93  (0.143) 1.85  (0.235)
Day 2/0Hr 1.92  (0.197) 1.93  (0.271) 1.94  (0.182) 1.81  (0.225)
Day 3/0Hr 1.90  (0.204) 1.89  (0.257) 1.94  (0.179) 1.83  (0.218)
11.Secondary Outcome
Title Serum Calcium (S-Ca) Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 9.46  (0.595) 9.37  (0.341) 9.48  (0.337) 9.50  (0.469)
Day 2/0 Hr 9.39  (0.439) 9.36  (0.507) 9.33  (0.388) 9.22  (0.466)
Day 3/0 hr 9.51  (0.544) 9.33  (0.360) 9.30  (0.397) 9.05  (0.425)
12.Secondary Outcome
Title Serum Sodium (S-Na) Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mmol/L
Baseline 139.4  (2.84) 139.1  (3.65) 140.0  (3.09) 137.7  (3.45)
Day 2/0 hr 140.1  (3.24) 138.8  (2.04) 140.1  (3.83) 138.6  (3.37)
Day 3/0 hr 140.0  (3.36) 138.5  (2.28) 140.0  (3.91) 139.6  (3.50)
13.Secondary Outcome
Title Serum Bicarbonate (HCO3) Levels
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily Zirconium Silicate 3 g Three Times Daily Sodium Zirconium Cyclosilicate 10 g Three Times Daily
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Zirconium Silicate (ZS) 3 g TID, three times daily as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mmol/L
Baseline 28.1  (2.99) 28.6  (3.11) 28.1  (3.26) 27.4  (3.58)
Day 2/0 hr 28.6  (2.46) 29.2  (3.51) 28.3  (3.15) 30.1  (1.79)
Day 3/0 hr 29.0  (3.66) 28.3  (2.96) 28.7  (3.25) 30.1  (2.31)
14.Secondary Outcome
Title 24-hour Urinary Excretion of Potassium
Hide Description 24-hour urinary excretion of potassium on Study Days 1 and Day 2
Time Frame 24 and 48 hours post study drug dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily Zirconium Silicate 3 g Three Times Daily Sodium Zirconium Cyclosilicate 10 g Three Times Daily
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Zirconium Silicate (ZS) 3 g TID, three times daily as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mmol/24 hour
Baseline 56.5  (33.96) 62.4  (31.51) 58.9  (20.44) 46.9  (23.67)
Study Day 1 64.7  (28.02) 89.4  (46.62) 60.5  (25.42) 41.0  (20.49)
Study Day 2 65.4  (29.23) 86.6  (52.64) 58.1  (24.77) 31.1  (16.55)
15.Secondary Outcome
Title 24-hour Urinary Excretion of Sodium
Hide Description 24-hour urinary excretion of sodium on Study Days 1 and Day 2
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily Zirconium Silicate 3 g Three Times Daily Sodium Zirconium Cyclosilicate 10 g Three Times Daily
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Zirconium Silicate (ZS) 3 g TID, three times daily as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mmol/24 hour
Baseline 145  (93.05) 132.8  (51.09) 124.0  (46.24) 114.8  (49.0)
Study Day 1 169.4  (88.90) 173.7  (64.02) 136.6  (79.5) 141.0  (68.05)
Study Day 2 181.8  (101.42) 181.5  (101.63) 132.5  (63.06) 140.2  (66.86)
16.Secondary Outcome
Title 24-hour Urinary Excretion of Urea Nitrogen
Hide Description 24-hour urinary excretion of urea nitrogen on Study Days 1 and Day 2
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) Sodium Zirconium Cyclosilicate (ZS) 0.3 g Three Times Daily Zirconium Silicate 3 g Three Times Daily Sodium Zirconium Cyclosilicate 10 g Three Times Daily
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Zirconium Silicate (ZS) 3 g TID, three times daily as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: g/24 hour
Baseline 7.66  (3.622) 7.59  (2.768) 7.03  (2.679) 6.74  (2.618)
Day 1 8.30  (3.832) 8.51  (5.549) 7.99  (3.929) 7.80  (3.460)
Day 2 10.37  (6.585) 8.68  (2.475) 8.57  (3.453) 7.49  (3.077)
17.Secondary Outcome
Title 24-hour Urinary Excretion of Creatinine
Hide Description 24-hour urinary excretion of creatinine on Study Days 1 and Day 2
Time Frame 48 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all subjects that were randomized, received any investigational product, and had S-K levels determined at 48 hours.
Arm/Group Title Placebo (Combined All Three Cohorts) 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
Hide Arm/Group Description:
Placebo randomized to mimic escalating doses of experimental drug administered three times a day (TID).
Sodium zirconium cyclosilicate 0.3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 3 g three times daily, orally as a suspension in water
Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
Overall Number of Participants Analyzed 30 12 24 24
Mean (Standard Deviation)
Unit of Measure: mg/24 hour
Baseline 1175.39  (482.708) 1149.00  (483.740) 1126.26  (446.745) 1015.67  (471.275)
Day 1 1157.12  (506.515) 1027.50  (301.315) 996.45  (442.333) 1008.25  (428.524)
Day 2 1270.71  (544.596) 1092.23  (411.469) 1050.29  (344.882) 1028.79  (430.408)
Time Frame Study Days 1 to 7
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 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
Hide Arm/Group Description Placebo randomized to mimic escalating doses of experimental drug administered 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, orally as a suspension in water Sodium zirconium cyclosilicate 10 g three times daily, orally as a suspension in water
All-Cause Mortality
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)      0/12 (0.00%)      0/24 (0.00%)      0/24 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/30 (0.00%)      0/12 (0.00%)      0/24 (0.00%)      0/24 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/30 (10.00%)      1/12 (8.33%)      3/24 (12.50%)      8/24 (33.33%)    
Blood and lymphatic system disorders         
Anaemia  1  0/30 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1
Gastrointestinal disorders         
Constipation  1  0/30 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0
Diarrhea  1  0/30 (0.00%)  0 1/12 (8.33%)  1 0/24 (0.00%)  0 1/24 (4.17%)  1
Dyspepsia  1  0/30 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1
Nausea  1  1/30 (3.33%)  1 0/12 (0.00%)  0 1/24 (4.17%)  1 2/24 (8.33%)  2
Vomiting  1  1/30 (3.33%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0 3/24 (12.50%)  3
Abdominal tenderness  1  1/30 (3.33%)  2 0/12 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0
Abdominal pain  1  0/30 (0.00%)  0 1/12 (8.33%)  2 0/24 (0.00%)  0 0/24 (0.00%)  0
Infections and infestations         
Urinary tract infection  1 [1]  0/30 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1 2/24 (8.33%)  2
Investigations         
Aspartate aminotransferae increased  1  0/30 (0.00%)  0 0/12 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Pain in extremity  1  0/30 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1
Nervous system disorders         
Headache  1  1/30 (3.33%)  1 0/12 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0
Vascular disorders         
Hypertension  1  0/30 (0.00%)  0 0/12 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1
1
Term from vocabulary, MedDRA 15.1E
Indicates events were collected by systematic assessment
[1]
All participants that had reported adverse event of urinary tract infection had screening urinalysis (Study Day 1) that was positive for bacterial culture
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: AstraZeneca Clinical Study Information Center
Organization: ZS Pharma, Inc
Phone: 1-877-240-9479
Responsible Party: ZS Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01493024     History of Changes
Other Study ID Numbers: ZS-002
First Submitted: December 12, 2011
First Posted: December 15, 2011
Results First Submitted: July 18, 2017
Results First Posted: June 29, 2018
Last Update Posted: June 29, 2018