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Trial record 18 of 119 for:    ZIRCONIUM

Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02088073
Recruitment Status : Completed
First Posted : March 14, 2014
Results First Posted : December 7, 2018
Last Update Posted : December 7, 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
Condition Hyperkalemia
Interventions Drug: Sodium zirconium cyclosilicate
Drug: Placebo
Enrollment 258
Recruitment Details Participants took part in the study at 44 sites in the United States, Australia, and South Africa from 31 March 2014 to 08 August 2014
Pre-assignment Details Subjects with hyperkalemia (i-STAT potassium value ≥ 5.1 mmol/L) were enrolled in the Acute Phase (AP) and were to be treated with ZS 10 g TID for the 48 hours.Subjects who achieved normokalemia during the AP were randomized to 1 of 3 doses of ZS (5 g, 10 g,or 15 g) or placebo for a further 28 days (Maintenance Phase [MP]).
Arm/Group Title ZS 10 g Three Times Daily (Acute Phase) Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description Sodium zirconium cyclosilicate (ZS) 10 g, three times daily (TID), orally as a suspension for 48 hours. Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive. Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive. Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive. Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Period Title: Acute Phase
Started 258 0 0 0 0
Completed 251 0 0 0 0
Not Completed 7 0 0 0 0
Reason Not Completed
Withdrawal by Subject             5             0             0             0             0
Hyperkalemia             2             0             0             0             0
Period Title: Maintanance Phase
Started 0 85 45 51 56
Completed 0 [1] 75 40 44 49
Not Completed 0 10 5 7 7
Reason Not Completed
Withdrawal by Subject             0             2             0             0             0
Adverse Event             0             0             3             0             1
Physician Decision             0             0             0             0             1
Sponsor's decision             0             2             0             2             1
Hypo- or hyperkalemia             0             3             0             3             1
Miscellaneous             0             2             1             2             1
Met ECG withdrawal criteria             0             0             1             0             2
Subject compliance             0             1             0             0             0
[1]
251 subjects completed the AP; 240 were eligible to enter the MP. 237 entered the MP.
Arm/Group Title ZS 10 g Three Times Daily (Acute Phase) Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase) Total
Hide Arm/Group Description Sodium zirconium cyclosilicate (ZS) 10 g, three times daily (TID), orally as a suspension for 48 hours. Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive. Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive. Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive. Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive. Total of all reporting groups
Overall Number of Baseline Participants 258 85 45 51 56 495
Hide Baseline Analysis Population Description
Some participants contributed to more than one baseline group. 258 participants entered the acute phase; 251 completed the acute phase. Of these 251 participants, 240 were eligible for the maintenance phase. Three participants did not enter the maintenance phase; 237 participants were randomized for the maintenance phase.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 258 participants 85 participants 45 participants 51 participants 56 participants 495 participants
Acute Phase 64.0  (12.72) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) 64.0  (12.72)
Maintenance Phase NA [2]   (NA) 64.3  (12.13) 61.5  (16.89) 63.8  (9.97) 64.9  (12.85) 63.80  (13.01)
[1]
This field does not apply to the Acute Phase of the study.
[2]
This field does not apply to the Maintenance Phase of the study.
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 85 participants 45 participants 51 participants 56 participants 495 participants
Female, Acute Phase 109 0 0 0 0 109
Male, Acute Phase 149 0 0 0 0 149
Female, Maintenance Phase 0 41 18 24 16 99
Male, Maintenance Phase 0 44 27 27 40 138
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 85 participants 45 participants 51 participants 56 participants 495 participants
White, Acute Phase 215 0 0 0 0 215
Black or African American, Acute Phase 37 0 0 0 0 37
Asian, Acute Phase 5 0 0 0 0 5
Native Hawaiian or other Pacific Islander, AP 1 0 0 0 0 1
Other, Acute Phase 2 0 0 0 0 2
Multiple Races indicated, Acute Phase 1 0 0 0 0 1
White, Maintenance Phase 0 73 36 44 46 199
Black or African American, Maintenance Phase 0 10 8 5 9 32
Asian, Maintenance Phase 0 3 0 1 1 5
Native Hawaiian or other Pacific Islander, MP 0 1 0 0 0 1
Other, Maintenance Phase 0 0 1 1 0 2
Multiple Races indicated, Maintenance Phase 0 1 0 0 0 1
Baseline Serum potassium ( S-K ) levels during both the Acute and Maintenance phases  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 85 participants 45 participants 51 participants 56 participants 495 participants
<5.5 mmol/L, Acute Phase 119 0 0 0 0 119
5.5-<6.0 mmol/L, Acute Phase 100 0 0 0 0 100
≥ 6.0 mmol/L, Acute Phase 39 0 0 0 0 39
<5.5 mmol/L, Maintenance Phase 0 43 23 19 24 109
5.5-<6.0 mmol/L, Maintenance Phase 0 30 17 23 26 96
≥ 6.0 mmol/L, Maintenance Phase 0 12 5 9 6 32
eGFR at baseline during both the Acute and Maintenance phases  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 85 participants 45 participants 51 participants 56 participants 495 participants
<60 mL/min, Acute Phase 179 0 0 0 0 179
≥ 60 mL/min, Acute Phase 72 0 0 0 0 72
Not reported, Acute Phase 7 0 0 0 0 7
<60 mL/min, Maintenance Phase 0 52 31 38 41 162
≥ 60 mL/min, Maintenance Phase 0 28 12 13 15 68
Not reported, Maintenance Phase 0 5 2 0 0 7
Etiology of elevated S-K levels during both the Acute and Maintenance phases   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 258 participants 85 participants 45 participants 51 participants 56 participants 495 participants
RAAS inhibitor medication, Acute Phase 180 0 0 0 0 180
Diabetes mellitus, Acute Phase 170 0 0 0 0 170
Chronic kidney disease, Acute Phase 169 0 0 0 0 169
Heart failure, Acute Phase 94 0 0 0 0 94
RAAS inhibitor medication, Maintenance Phase 0 61 33 36 33 163
Diabetes mellitus, Maintenance Phase 0 54 26 38 39 157
Chronic kidney disease, Maintenance Phase 0 50 29 36 37 152
Heart failure, Maintenance Phase 0 26 18 18 25 87
[1]
Measure Description: Categories not mutually exclusive
1.Primary Outcome
Title Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population).
Hide Description The least squares means (LSMeans) are dervied from a mixed effects model of serial log transformed S-K values between Days 8 and 29 with patients as a random effect and the following fixed effects terms: MP treatment group; AP baseline eGFR; AP and MP baseline S-K levels, age categories (<55, 55-64, >= 65 years); and binary indicators for RAAS inhibitors use, CKD, CHF, and DM. The LSmeans estimate obtained from the above model is back-transformed and presented as the lsmeans of all available S-K values during the Maintenance phase study Days 8 to 29.
Time Frame 22 Days; Maintenance Phase Days 8 - 29, inclusive.
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized patients who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/L
5.0603
(4.9646 to 5.1578)
4.7544
(4.6350 to 4.8769)
4.5081
(4.4005 to 4.6184)
4.3742
(4.2754 to 4.4753)
2.Secondary Outcome
Title The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT).
Hide Description The number of normokalemic days during the Maintenance Phase Study Days 8 to 29 is calculated assuming that the interval between assessments is normokalemic only if both the beginning and end assessments for that time interval display normal S-K values (i.e. 3.5 - 5.0 mmol/L)
Time Frame 22 days; Maintenance Phase Day 8 - 29, inclusive.
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized patients who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Mean (Standard Deviation)
Unit of Measure: Days
7.4  (8.0) 13.4  (7.57) 13.9  (7.91) 16.8  (6.99)
3.Secondary Outcome
Title Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit .
Hide Description [Not Specified]
Time Frame Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Mean (Standard Deviation)
Unit of Measure: mmol/L
AP Baseline S-K level 5.55  (0.471) 5.53  (0.357) 5.58  (0.423) 5.55  (0.331)
MP Study Day 2 Mean Change -0.86  (0.508) -1.03  (0.408) -1.25  (0.471) -1.12  (0.477)
MP Study Day 8 Mean Change -0.49  (0.549) -0.72  (0.552) -1.09  (0.629) -1.20  (0.592)
MP Study Day 12 Mean Change -0.41  (0.508) -0.75  (0.516) -1.11  (0.663) -1.20  (0.665)
MP Study Day 15 Mean Change -0.48  (0.612) -0.77  (0.492) -1.11  (0.652) -1.19  (0.627)
MP Study Day 19 Mean Change -0.45  (0.549) -0.79  (0.520) -1.04  (0.581) -1.07  (0.575)
MP Study Day 22 Mean Change -0.45  (0.578) -0.71  (0.543) -0.93  (0.653) -1.05  (0.586)
MP Study Day 26 Mean Change -0.43  (0.552) -0.65  (0.448) -0.87  (0.697) -1.03  (0.597)
MP Study Day 29 Mean Change -0.47  (0.499) -0.69  (0.500) -1.08  (0.704) -1.12  (0.571)
MP Study Day 29/Exit Mean Change -0.44  (0.515) -0.77  (0.559) -1.10  (0.813) -1.19  (0.659)
4.Secondary Outcome
Title Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive .
Hide Description [Not Specified]
Time Frame Acute Phase baseline to Maintenance Phase Study Day 2 to Day 29/Exit, inclusive.
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Mean (Standard Deviation)
Unit of Measure: Percent Change
MP Study Day 2 Percent Change -15.11  (8.154) -18.53  (6.941) -22.19  (7.897) -20.04  (7.959)
MP Study Day 8 Percent Change -8.45  (9.492) -12.84  (9.700) -19.16  (10.708) -21.29  (10.135)
MP Study Day 12 Percent Change -7.22  (8.967) -13.36  (8.949) -19.45  (11.072) -21.22  (11.368)
MP Study Day 15 Percent Change -8.28  (10.739) -13.73  (8.485) -19.33  (10.884) -21.19  (10.675)
MP Study Day 19 Percent Change -7.87  (9.554) -14.08  (8.822) -18.29  (9.707) -19.10  (9.957)
MP Study Day 22 Percent Change -7.74  (9.992) -12.65  (9.591) -16.25  (11.292) -18.65  (10.034)
MP Study Day 26 Percent Change -7.54  (9.386) -11.83  (8.025) -15.18  (11.988) -18.28  (10.271)
MP Study Day 29 Percent Change -8.23  (8.586) -12.49  (8.770) -18.83  (11.951) -19.80  (9.503)
MP Study Day 29/Exit Percent Change -7.68  (8.940) -13.85  (9.568) -19.28  (14.099) -21.06  (11.086)
5.Secondary Outcome
Title Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.
Hide Description [Not Specified]
Time Frame Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Mean (Standard Deviation)
Unit of Measure: mmol/L
MP Baseline S-K level 4.55  (0.427) 4.51  (0.357) 4.38  (0.407) 4.45  (0.372)
MP Study Day 2 Mean change 0.13  (0.411) -0.01  (0.372) -0.04  (0.384) -0.02  (0.400)
MP Study Day 8 Mean change 0.50  (0.538) 0.30  (0.467) 0.12  (0.523) -0.10  (0.535)
MP Study Day 12 Mean change 0.60  (0.580) 0.26  (0.541) 0.10  (0.594) -0.11  (0.572)
MP Study Day 15 Mean change 0.54  (0.694) 0.25  (0.535) 0.11  (0.552) -0.10  (0.546)
MP Study Day 19 Mean change 0.55  (0.672) 0.22  (0.580) 0.17  (0.483) 0.01  (0.605)
MP Study Day 22 Mean change 0.55  (0.627) 0.30  (0.563) 0.27  (0.650) 0.03  (0.579)
MP Study Day 26 Mean change 0.55  (0.623) 0.34  (0.565) 0.33  (0.673) 0.05  (0.594)
MP Study Day 29 Mean change 0.52  (0.545) 0.28  (0.664) 0.14  (0.668) -0.04  (0.554)
MP Study Day 29/Exit Mean change 0.56  (0.582) 0.25  (0.645) 0.11  (0.768) -0.09  (0.598)
6.Secondary Outcome
Title Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.
Hide Description [Not Specified]
Time Frame Maintenance phase baseline to Maintenance Phase Study Day 29/Exit, inclusive.
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Mean (Standard Deviation)
Unit of Measure: Percent Change
MP Study Day 2 Percent change 3.39  (9.044) 0.06  (8.036) -0.51  (8.862) -0.20  (8.984)
MP Study Day 8 Percent change 11.64  (12.291) 6.93  (10.486) 3.05  (12.346) -1.74  (12.043)
MP Study Day 12 Percent change 13.70  (13.072) 6.38  (12.287) 2.85  (13.595) -2.00  (12.836)
MP Study Day 15 Percent change 12.51  (15.693) 5.95  (12.169) 2.93  (12.662) -1.89  (12.118)
MP Study Day 19 Percent change 12.96  (15.791) 5.33  (12.934) 4.28  (11.231) .095  (13.697)
MP Study Day 22 Percent change 12.84  (14.342) 6.98  (12.774) 6.79  (15.174) 1.39  (12.782)
MP Study Day 26 Percent change 13.03  (14.566) 7.98  (12.932) 8.08  (15.516) 1.88  (16.641)
MP Study Day 29 Percent change 12.09  (13.116) 6.12  (14.424) 3.02  (17.785) -1.43  (13.664)
MP Study Day 29/Exit Percent change 12.97  (13.116) 6.12  (14.424) 3.02  (17.785) -1.43  (13.664)
7.Secondary Outcome
Title Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L)
Hide Description [Not Specified]
Time Frame Maintenance Phase baseline to maintenance Phase Study Day 29/Exit.
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Median (95% Confidence Interval)
Unit of Measure: Days
7
(6 to 7)
14
(7 to 28)
NA [1] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
The Median time was not reached in the ZS 10 g group because fewer than 50% of patients in the group had a hyperkalemic event before the end of the Maintenance Phase.
[2]
The Median time was not reached in the ZS 15 g group because fewer than 50% of patients in the group had a hyperkalemic event before the end of the Maintenance Phase.
8.Secondary Outcome
Title Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8
Hide Description [Not Specified]
Time Frame 22 days; Maintenance Phase Day 8 - 29
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Mean (95% Confidence Interval)
Unit of Measure: mmol/L
0.06392
(0.05804 to 0.06980)
0.06367
(0.05574 to 0.07159)
0.07708
(0.06941 to 0.08474)
0.06849
(0.06126 to 0.07571)
9.Secondary Outcome
Title Proportion of Subjects Who Remained Normokalemic During Maintenance Phase
Hide Description [Not Specified]
Time Frame Maintenance Phase Study Days 1, 2, 5, 8, 12, 15, 19, 22, 26, 29, and 35, inclusive.
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Measure Type: Number
Unit of Measure: Proportion of subjects
Baseline 0.866 0.933 0.920 0.926
MP Study Day 2 0.84 0.933 0.918 0.944
MP Study Day 8 0.481 0.711 0.820 0.852
MP Study Day 12 0.400 0.750 0.787 0.849
MP Study Day 15 0.438 0.705 0.851 0.827
MP Study Day 19 0.449 0.744 0.787 0.882
MP Study Day 22 0.442 0.674 0.667 0.882
MP Study Day 26 0.486 0.738 0.711 0.843
MP Study Day 29 0.507 0.667 0.816 0.907
MP Study Day 29/Exit 0.476 0.711 0.760 0.852
10.Secondary Outcome
Title Median Time to Relapse in S-K Values
Hide Description Median time to relapse in S-K values (return to original Acute Phase S-K baseline value)
Time Frame Maintenance phase Study Day 1 to Study Day 29/Exit.
Hide Outcome Measure Data
Hide Analysis Population Description
Maintenance Phase Intent- to-Treat (MP-ITT) population: all randomized subjects who received at least 1 Maintenance Phase dose and had at least 1 observed S-K assessment on or after Study Day 8.
Arm/Group Title Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description:
Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive.
Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
Overall Number of Participants Analyzed 82 45 50 54
Median (95% Confidence Interval)
Unit of Measure: Days
19
(12 to 28)
29 [1] 
(29 to NA)
NA [2] 
(NA to NA)
NA [3] 
(NA to NA)
[1]
The confidence interval for the median is based on when the lower and upper limits of the confidence interval for survival function reach 50%. However, the upper limit for survival function in the ZS 5 g QD did not reach 50% in the Maintenance Phase.
[2]
Fewer than 50% of patients in the ZS 10 g QD had relapsed at the end of the Maintenance Phase. Therefore, median was not reached.
[3]
Fewer than 50% of patients in the ZS 15 g QD had relapsed at the end of the Maintenance Phase. Therefore, median was not reached.
11.Secondary Outcome
Title Exponential Rate of Change in S-K Values During the Acute Phase at 24 Hours and 48 Hours of Study Drug Treatment.
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Time Frame Acute Phase 24 hours and Acute Phase 48 hours.
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Acute Phase ITT Population included all subjects who received at least 1 Acute Phase dose and had any post-baseline S-K levels after receiving the investigational product during the first 48 hours.
Arm/Group Title Acute Phase: ZS 10 g TID
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ZS (sodium zirconium cyclosilicate) 10 g, three times a day, orally as suspension in water for 48 hours.
Overall Number of Participants Analyzed 258
Mean (Standard Error)
Unit of Measure: log(mmol/L/hour)
24 hours after start of ZS dosing -0.00373  (0.000231)
48 hours of start of ZS dosing -0.00324  (0.000130)
12.Secondary Outcome
Title Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.
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Time Frame All measured time intervals post dose during the Acute Phase.
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Acute Phase ITT Population included all subjects who received at least 1 Acute Phase dose and had any post-baseline S-K levels after receiving the investigational product during the first 48 hours.
Arm/Group Title Acute Phase: ZS 10 g TID
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ZS (sodium zirconium cyclosilicate) 10 g, three times a day, orally as suspension in water for 48 hours.
Overall Number of Participants Analyzed 258
Mean (Standard Deviation)
Unit of Measure: mmol/L
Acute phase baseline 5.55  (0.449)
1 hour after start of ZS dosing Mean change -0.23  (0.435)
2 hours after start of ZS dosing Mean change -0.41  (0.440)
4 hours after start of ZS dosing Mean change -0.51  (0.405)
24 hours after start of ZS dosing Mean change -0.68  (0.448)
1 hour after 1st dose Study Day 2 Mean change -0.75  (0.444)
48 hours after start of ZS dosing Mean change -1.05  (0.510)
13.Secondary Outcome
Title Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.
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Time Frame All measured time intervals post dose during the Acute Phase.
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Acute Phase ITT Population included all subjects who received at least 1 Acute Phase dose and had any post-baseline S-K levels after receiving the investigational product during the first 48 hours.
Arm/Group Title Acute Phase: ZS 10 g TID
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ZS (sodium zirconium cyclosilicate) 10 g, three times a day, orally as suspension in water for 48 hours.
Overall Number of Participants Analyzed 258
Mean (Standard Deviation)
Unit of Measure: Percent Change
1 hour after start of ZS dosing Percent change -3.91  (7.741)
2 hours after start of ZS dosing Percent change -7.13  (7.706)
4 hours after start of ZS dosing Percent change -9.00  (7.123)
24 hours after start of ZS dosing Percent change -12.03  (7.808)
1 hour after 1st dose Study Day 2 Percent change -13.41  (7.720)
48 hours after start of ZS dosing Percent change -18.56  (8.506)
14.Secondary Outcome
Title Proportion of Subjects Who Achieve Normokalemia During the Acute Phase at 24 and 48 Hours After Start of Dosing
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Time Frame Through 48 hours acute phase
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Acute Phase ITT Population included all subjects who received at least 1 Acute Phase dose and had any post-baseline S-K levels after receiving the investigational product during the first 48 hours.
Arm/Group Title Acute Phase: ZS 10 g TID
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ZS (sodium zirconium cyclosilicate) 10 g, three times a day, orally as suspension in water for 48 hours.
Overall Number of Participants Analyzed 258
Measure Type: Number
Unit of Measure: Proportion of subjects
24 hours after start of dosing 0.661
48 hours after of start dosing 0.88
15.Secondary Outcome
Title Median Time to Normalization (3.50-5.0 mmol/L) in S-K Levels in the 48 Hours of Initial Treatment
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Time Frame Through 48 hours acute phase
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Hide Analysis Population Description
Acute Phase ITT Population included all subjects who received at least 1 Acute Phase dose and had any post-baseline S-K levels after receiving the investigational product during the first 48 hours.
Arm/Group Title Acute Phase: ZS 10 g TID
Hide Arm/Group Description:
ZS (sodium zirconium cyclosilicate) 10 g, three times a day, orally as a suspension for 48 hours.
Overall Number of Participants Analyzed 258
Median (95% Confidence Interval)
Unit of Measure: Hours
2.17
(2 to 3.97)
Time Frame All adverse events were collected beginning with the first administration of study drug and through end of study treatment follow up visit. End of treatment study follow up visit was 7 days +/- 1 day after last dose of investigational product.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ZS 10 g TID (Acute Phase) Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Hide Arm/Group Description ZS (sodium zirconium cyclosilicate) 10 g, three times a day, orally as suspension in water for 48 hours. Placebo to mimic doses of experimental drug once daily between Days 8 to 29, inclusive. Sodium zirconium cyclosilicate (ZS) 5 g, once daily, orally as a suspension between Days 8 to 29, inclusive. Sodium zirconium cyclosilicate (ZS) 10 g, once daily, orally as a suspension between Days 8 to 29, inclusive. Sodium zirconium cyclosilicate (ZS) 15 g, once daily, orally as a suspension between Day 8 to 29, inclusive.
All-Cause Mortality
ZS 10 g TID (Acute Phase) Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ZS 10 g TID (Acute Phase) Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/258 (0.00%)   0/85 (0.00%)   5/45 (11.11%)   2/51 (3.92%)   3/56 (5.36%) 
Cardiac disorders           
Cardiac failure congestive  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  0/56 (0.00%) 
Myocardial infarction  1  0/258 (0.00%)  0/85 (0.00%)  0/45 (0.00%)  1/51 (1.96%)  0/56 (0.00%) 
Gastrointestinal disorders           
Small intestinal obstruction  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  0/56 (0.00%) 
General disorders           
Generalized edema  1  0/258 (0.00%)  0/85 (0.00%)  0/45 (0.00%)  0/51 (0.00%)  1/56 (1.79%) 
Hepatobiliary disorders           
Hepatotoxicity  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  0/56 (0.00%) 
Infections and infestations           
Cellulitis  1  0/258 (0.00%)  0/85 (0.00%)  0/45 (0.00%)  1/51 (1.96%)  0/56 (0.00%) 
Pneumonia  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  1/56 (1.79%) 
Psychiatric disorders           
Confusional state  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  0/56 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Dyspnoea  1  0/258 (0.00%)  0/85 (0.00%)  0/45 (0.00%)  0/51 (0.00%)  1/56 (1.79%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
ZS 10 g TID (Acute Phase) Placebo Comparator (Maintenance Phase) ZS 5 g Once Daily (Maintenance Phase) ZS 10 g Once Daily (Maintenance Phase) ZS 15 g Once Daily (Maintenance Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/258 (3.49%)   25/85 (29.41%)   20/45 (44.44%)   15/51 (29.41%)   25/56 (44.64%) 
Blood and lymphatic system disorders           
Anemia  1  0/258 (0.00%)  0/85 (0.00%)  0/45 (0.00%)  0/51 (0.00%)  3/56 (5.36%) 
Cardiac disorders           
Cardiac failure congestive  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  1/56 (1.79%) 
Gastrointestinal disorders           
Constipation  1  2/258 (0.78%)  6/85 (7.06%)  0/45 (0.00%)  1/51 (1.96%)  1/56 (1.79%) 
Diarrhoea  1  3/258 (1.16%)  1/85 (1.18%)  0/45 (0.00%)  0/51 (0.00%)  2/56 (3.57%) 
Abdominal pain  1  0/258 (0.00%)  1/85 (1.18%)  1/45 (2.22%)  0/51 (0.00%)  0/56 (0.00%) 
Dyspepsia  1  0/258 (0.00%)  0/85 (0.00%)  2/45 (4.44%)  0/51 (0.00%)  0/56 (0.00%) 
Nausea  1  2/258 (0.78%)  1/85 (1.18%)  0/45 (0.00%)  0/51 (0.00%)  1/56 (1.79%) 
Vomiting  1  0/258 (0.00%)  1/85 (1.18%)  1/45 (2.22%)  0/51 (0.00%)  0/56 (0.00%) 
General disorders           
Edema  1 [1]  0/258 (0.00%)  2/85 (2.35%)  1/45 (2.22%)  3/51 (5.88%)  8/56 (14.29%) 
Fatigue  1  0/258 (0.00%)  0/85 (0.00%)  0/45 (0.00%)  5/51 (9.80%)  6/56 (10.71%) 
Generalised Oedema  1  0/258 (0.00%)  0/85 (0.00%)  0/45 (0.00%)  0/51 (0.00%)  2/56 (3.57%) 
Oedema peripheral  1  0/258 (0.00%)  2/85 (2.35%)  0/45 (0.00%)  3/51 (5.88%)  6/56 (10.71%) 
Infections and infestations           
Nasopharyngitis  1  0/258 (0.00%)  1/85 (1.18%)  0/45 (0.00%)  0/51 (0.00%)  3/56 (5.36%) 
Upper respiratory infection  1  1/258 (0.39%)  1/85 (1.18%)  3/45 (6.67%)  1/51 (1.96%)  1/56 (1.79%) 
Influenza  1  0/258 (0.00%)  0/85 (0.00%)  0/45 (0.00%)  1/51 (1.96%)  2/56 (3.57%) 
Pneumonia  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  1/56 (1.79%) 
Urinary tract infection bacterial  1  0/258 (0.00%)  1/85 (1.18%)  0/45 (0.00%)  0/51 (0.00%)  1/56 (1.79%) 
Investigations           
Electrocardiogram QT prolonged  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  1/56 (1.79%) 
Metabolism and nutrition disorders           
Gout  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  1/51 (1.96%)  1/56 (1.79%) 
Hypocalcaemia  1  0/258 (0.00%)  2/85 (2.35%)  0/45 (0.00%)  0/51 (0.00%)  0/56 (0.00%) 
Hypoglycaemia  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  1/56 (1.79%) 
Musculoskeletal and connective tissue disorders           
Pain in extremity  1  0/258 (0.00%)  1/85 (1.18%)  0/45 (0.00%)  1/51 (1.96%)  1/56 (1.79%) 
Nervous system disorders           
Dizziness  1  2/258 (0.78%)  1/85 (1.18%)  0/45 (0.00%)  1/51 (1.96%)  1/56 (1.79%) 
Renal and urinary disorders           
Dysuria  1  0/258 (0.00%)  1/85 (1.18%)  1/45 (2.22%)  0/51 (0.00%)  0/56 (0.00%) 
Haematuria  1  0/258 (0.00%)  1/85 (1.18%)  0/45 (0.00%)  0/51 (0.00%)  1/56 (1.79%) 
Renal failure  1  0/258 (0.00%)  0/85 (0.00%)  2/45 (4.44%)  0/51 (0.00%)  0/56 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Asthma  1  0/258 (0.00%)  1/85 (1.18%)  1/45 (2.22%)  0/51 (0.00%)  0/56 (0.00%) 
Dysponea  1  0/258 (0.00%)  0/85 (0.00%)  1/45 (2.22%)  0/51 (0.00%)  1/56 (1.79%) 
Vascular disorders           
Hypertension  1  0/258 (0.00%)  1/85 (1.18%)  2/45 (4.44%)  1/51 (1.96%)  2/56 (3.57%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
[1]
Including generalized and peripheral edema
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
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Name/Title: AstraZeneca Clinical Study Information Center
Organization: ZS Pharma, Inc.
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
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Responsible Party: ZS Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02088073     History of Changes
Other Study ID Numbers: ZS-004
First Submitted: March 12, 2014
First Posted: March 14, 2014
Results First Submitted: July 18, 2017
Results First Posted: December 7, 2018
Last Update Posted: December 7, 2018