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Trial record 20 of 119 for:    ZIRCONIUM

Open-label Safety & Efficacy of ZS (Sodium Zirconium Cyclosilicate)10g qd to Extend Study ZS-004 in Hyperkalemia.

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ClinicalTrials.gov Identifier: NCT02107092
Recruitment Status : Completed
First Posted : April 8, 2014
Results First Posted : August 15, 2018
Last Update Posted : August 15, 2018
Sponsor:
Information provided by (Responsible Party):
ZS Pharma, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Condition Hyperkalemia
Intervention Drug: Sodium Zirconium Cyclosilicate
Enrollment 123
Recruitment Details Participants took part in the study at 30 outpatient sites in the United States, Australia and South Africa from 10 May 2014 to 14 July 2015.
Pre-assignment Details Participants that completed Study ZS-004 (NCT02088073) Extended Dosing (ED) Phase Study Day 29 Visit or discontinued Study ZS-004 during the ED Phase due to hypo- or hyperkalemia, had a mean i-STAT potassium value between 3.5 and 6.2 mmol/L, and were able to start dosing in Study ZS-004E within 2 days after the last dose of study drug in ZS-004.
Arm/Group Title Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD
Hide Arm/Group Description ZS 10g QD starting dose. ZS dose was increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g every other day (QOD) if i-STAT potassium values increased to > 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Period Title: Overall Study
Started 123
Completed 79
Not Completed 44
Reason Not Completed
Miscellaneous             3
Subject compliance             3
Hypo-or hyperkalemia             2
Met ECG withdrawal criteria             3
Physician Decision             3
Lost to Follow-up             2
Withdrawal by Subject             9
Adverse Event             7
Expected progression of CKD             12
Arm/Group Title Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD
Hide Arm/Group Description ZS 10g QD starting dose. ZS dose was increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g every other day (QOD) if i-STAT potassium values increased to > 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Overall Number of Baseline Participants 121
Hide Baseline Analysis Population Description
2 subjects did not have any S-K measurements during the ED phase due to early termination and are excluded from baseline characteristics
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 121 participants
63.7  (12.29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
Female
51
  42.1%
Male
70
  57.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
Asian
2
   1.7%
Black or African American
11
   9.1%
White
107
  88.4%
Other
1
   0.8%
Study ZS-004 Acute Phase S-K baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
< 5.5 mmol/L
54
  44.6%
5.5-< 6.0 mmol/L
53
  43.8%
≥ 6.0 mmol/L
14
  11.6%
[1]
Measure Description: Acute Phase S-K baseline of participants in Study ZS-004
Acute Phase eGFR at baseline   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 121 participants
<60 mL/min
90
  74.4%
≥ 60 mL/min
31
  25.6%
[1]
Measure Description: Acute Phase baseline from Study ZS-004
Cormordid conditions and concomitant medications which may contirubute to hyperkalemia   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 121 participants
RAAS inhibitor medication 83
Diabetes mellitus 80
Chronic kidney disease 76
Heart failure 50
[1]
Measure Description: Categories are not mutually exclusive
1.Primary Outcome
Title Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L
Hide Description The proportions of subjects with average serum potassium (S-K) values ≤ 5.1 mmol/L during Extended Dosing Study Days 8 to 337, inclusive
Time Frame 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
Entered Extended Dosing Phase, received study drug and had post baseline S-K values during the Extended Dosing Phase. The analysis population includes 121 subjects, where there is one subject who only had end-of-study post-baseline measurement and therefore was not presented in the participants analyzed.
Arm/Group Title Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD
Hide Arm/Group Description:
ZS 10g QD starting dose. ZS dose was increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g every other day (QOD) if i-STAT potassium values increased to > 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Overall Number of Participants Analyzed 120
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of Participants
ED Study Day 8 Number Analyzed 120 participants
0.875
(0.802 to 0.928)
ED Study Day 15 Number Analyzed 118 participants
0.822
(0.741 to 0.886)
ED Study Day 22 Number Analyzed 118 participants
0.797
(0.713 to 0.865)
ED Study Day 29 Number Analyzed 116 participants
0.862
(0.786 to 0.919)
ED Study Day 36 Number Analyzed 112 participants
0.848
(0.768 to 0.909)
ED Study Day 43 Number Analyzed 111 participants
0.793
(0.705 to 0.864)
ED Study Day 50 Number Analyzed 108 participants
0.796
(0.708 to 0.868)
ED Study Day 57 Number Analyzed 107 participants
0.766
(0.675 to 0.843)
ED Study Day 85 Number Analyzed 88 participants
0.807
(0.709 to 0.833)
ED Study Day 113 Number Analyzed 84 participants
0.798
(0.696 to 0.877)
ED Study Day 141 Number Analyzed 81 participants
0.815
(0.713 to 0.892)
ED Study Day 169 Number Analyzed 70 participants
0.771
(0.656 to 0.863)
ED Study Day 197 Number Analyzed 68 participants
0.809
(0.695 to 0.894)
ED Day Study 225 Number Analyzed 65 participants
0.846
(0.735 to 0.924)
ED Study Day 253 Number Analyzed 63 participants
0.778
(0.655 to 0.873)
ED Study Day 281 Number Analyzed 60 participants
0.833
(0.715 to 0.917)
ED Study Day 309 Number Analyzed 58 participants
0.828
(0.706 to 0.914)
ED Study Day 337 Number Analyzed 51 participants
0.843
(0.714 to 0.930)
ED Study Day 337/Exit Number Analyzed 120 participants
0.783
(0.699 to 0.853)
ED Study Days 8-337 Average Number Analyzed 120 participants
0.883
(0.812 to 0.935)
2.Secondary Outcome
Title Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L
Hide Description The proportions of subjects with average S-K values ≤ 5.5 mmol/L during Extended Dosing Study Days 8 to 337, inclusive
Time Frame 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
Entered Extended Dosing Phase, received study drug and had post baseline S-K values during the Extended Dosing Phase. The analysis population includes 121 subjects, where there is one subject who only had end-of-study post-baseline measurement and therefore was not presented in the participants analyzed.
Arm/Group Title Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD
Hide Arm/Group Description:
ZS 10g QD starting dose. ZS dose was increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g every other day (QOD) if i-STAT potassium values increased to > 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
Overall Number of Participants Analyzed 120
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Proportion of Participants
ED Study Day 8 Number Analyzed 120 participants
0.950
(0.894 to 0.981)
ED Study Day 15 Number Analyzed 118 participants
0.932
(0.871 to 0.970)
ED Study Day 22 Number Analyzed 118 participants
0.975
(0.927 to 0.995)
ED Study Day 29 Number Analyzed 116 participants
0.957
(0.902 to 0.986)
ED Study Day 36 Number Analyzed 112 participants
0.955
(0.899 to 0.985)
ED Study Day 43 Number Analyzed 111 participants
0.946
(0.886 to 0.980)
ED Study Day 50 Number Analyzed 108 participants
0.935
(0.871 to 0.974)
ED Study Day 57 Number Analyzed 107 participants
0.944
(0.882 to 0.979)
ED Study Day 85 Number Analyzed 88 participants
0.943
(0.872 to 0.981)
ED Study Day 113 Number Analyzed 84 participants
0.940
(0.867 to 0.980)
ED Study Day 141 Number Analyzed 81 participants
0.938
(0.862 to 0.980)
ED Study Day 169 Number Analyzed 70 participants
0.929
(0.841 to 0.976)
ED Study Day 197 Number Analyzed 68 participants
0.941
(0.856 to 0.984)
ED Day Study 225 Number Analyzed 65 participants
0.985
(0.917 to 1.000)
ED Study Day 253 Number Analyzed 63 participants
0.937
(0.845 to 0.982)
ED Study Day 281 Number Analyzed 60 participants
0.950
(0.861 to 0.990)
ED Study Day 309 Number Analyzed 58 participants
0.914
(0.810 to 0.971)
ED Study Day 337 Number Analyzed 51 participants
0.980
(0.896 to 1.000)
ED Study Day 337/Exit Number Analyzed 120 participants
0.942
(0.884 to 0.976)
ED Study Days 8-337 Average Number Analyzed 120 participants
1.000
(0.970 to 1.000)
Time Frame Eleven months
Adverse Event Reporting Description The Extended Dosing Phase Safety Population was defined as all subjects who received at least 1 Extended Dosing Phase dose administration with any post-baseline Extended Dosing Phase safety data.
 
Arm/Group Title ZS (Sodium Zirconium Cyclosilicate) QD Extended Phase Dosing
Hide Arm/Group Description ZS 10g QD starting dose increased or decreased in increments/ decrements of 5g QD to maximum of 15g QD or minimum of 5g QOD if i-STAT potassium values increased to > 5.5 mmol/L or decreased to between 3.0 and 3.4 mmol/L, respectively.
All-Cause Mortality
ZS (Sodium Zirconium Cyclosilicate) QD Extended Phase Dosing
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ZS (Sodium Zirconium Cyclosilicate) QD Extended Phase Dosing
Affected / at Risk (%)
Total   24/123 (19.51%) 
Blood and lymphatic system disorders   
Anaemia  1  1/123 (0.81%) 
Cardiac disorders   
Acute myocardial infarction  1  1/123 (0.81%) 
Cardiac failure  1  1/123 (0.81%) 
Cardiac failure congestive  1  2/123 (1.63%) 
Myocardial infarction  1  1/123 (0.81%) 
Eye disorders   
Retinal artery occlusion  1  1/123 (0.81%) 
Gastrointestinal disorders   
Abdominal Pain  1  2/123 (1.63%) 
Gastritis haemorrhagic  1  1/123 (0.81%) 
General disorders   
Chest pain  1  1/123 (0.81%) 
Infections and infestations   
Diabetic foot infection  1  1/123 (0.81%) 
Gangrene  1  1/123 (0.81%) 
Lobar pneumonia  1  1/123 (0.81%) 
Localised infection  1  1/123 (0.81%) 
Morganella infection  1  1/123 (0.81%) 
Pneumonia  1  2/123 (1.63%) 
Sepsis  1  1/123 (0.81%) 
Tooth abscess  1  1/123 (0.81%) 
Urinary tract infection  1  2/123 (1.63%) 
Injury, poisoning and procedural complications   
Patella fracture  1  1/123 (0.81%) 
Metabolism and nutrition disorders   
Hyperkalaemia  1  1/123 (0.81%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Adenocarcinoma of colon  1  1/123 (0.81%) 
Nervous system disorders   
Cerebrovascular accident  1  1/123 (0.81%) 
Convulsion  1  1/123 (0.81%) 
Respiratory, thoracic and mediastinal disorders   
Chronic obstructive pulmonary disease  1  2/123 (1.63%) 
Pulmonary oedema  1  1/123 (0.81%) 
Skin and subcutaneous tissue disorders   
Dry gangrene  1  1/123 (0.81%) 
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 (Sodium Zirconium Cyclosilicate) QD Extended Phase Dosing
Affected / at Risk (%)
Total   82/123 (66.67%) 
Blood and lymphatic system disorders   
Anaemia  1  6/123 (4.88%) 
Cardiac disorders   
Cardiac failure  1  3/123 (2.44%) 
Gastrointestinal disorders   
Abdominal pain  1  3/123 (2.44%) 
Constipation  1  7/123 (5.69%) 
Diarrhoea  1  4/123 (3.25%) 
Nausea  1  4/123 (3.25%) 
Vomiting  1  4/123 (3.25%) 
General disorders   
Oedema  1  4/123 (3.25%) 
Oedema peripheral  1  10/123 (8.13%) 
Immune system disorders   
Seasonal allergy  1  3/123 (2.44%) 
Infections and infestations   
Gastroenteritis  1  3/123 (2.44%) 
Influenza  1  3/123 (2.44%) 
Pneumonia  1  3/123 (2.44%) 
Upper respiratory tract infection  1  5/123 (4.07%) 
Urinary tract infection  1  11/123 (8.94%) 
Investigations   
Blood urea increased  1  3/123 (2.44%) 
Metabolism and nutrition disorders   
Gout  1  4/123 (3.25%) 
Hyperlipidemia  1  4/123 (3.25%) 
Hypomagnesaemia  1  3/123 (2.44%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/123 (2.44%) 
Back pain  1  3/123 (2.44%) 
Muscle spasms  1  6/123 (4.88%) 
Nervous system disorders   
Dizzines  1  3/123 (2.44%) 
Headache  1  4/123 (3.25%) 
Respiratory, thoracic and mediastinal disorders   
Chronic obstructive pulmonary disease  1  3/123 (2.44%) 
Cough  1  3/123 (2.44%) 
Vascular disorders   
Hypertension  1  15/123 (12.20%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
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
Layout table for Results Point of Contact information
Name/Title: AstraZeneca Clinical Study Information Center
Organization: ZS Pharma, Inc.
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Layout table for additonal information
Responsible Party: ZS Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02107092     History of Changes
Other Study ID Numbers: ZS-004E
First Submitted: April 3, 2014
First Posted: April 8, 2014
Results First Submitted: July 13, 2017
Results First Posted: August 15, 2018
Last Update Posted: August 15, 2018