Open-label Safety and Efficacy of Sodium Zirconium Cyclosilicate for up to 12 Months

Study identifier:ZS-005

ClinicalTrials.gov identifier:NCT02163499

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Multicenter, Multi-Dose, Open-Label Maintenance of Long-Term Safety and Efficacy of Sodium Zirconium Cyclosilicate (ZS) in Hyperkalemia

Medical condition

Hyperkalemia

Phase

Phase 3

Healthy volunteers

Study drug

Sodium Zirconium Cyclosilicate

Sex

All

Actual Enrollment

751

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 30 Jun 2014

Primary Completion Date: 30 Nov 2016

Study Completion Date: 30 Nov 2016

Study design

Allocation: N/A
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care

Verification:

Verified 01 May 2018 by ZS Pharma, Inc.

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

- Provision of written informed consent.
- Over 18 years of age.
- Two consecutive i STAT potassium values, measured 60 (+/- 15) minutes
apart, both >/= 5.1 mmol/L and measured within 1 day before the first
dose of ZS on Acute Phase Study Day 1.
- Ability to have repeated blood draws or effective venous catheterization.
- Women of childbearing potential must be using 2 forms of medically
acceptable contraception (at least 1 barrier method) and have a negative
pregnancy test at Acute Phase Study Day 1. Women who are surgically
sterile or those who are postmenopausal for at least 2 years are not
considered to be of childbearing potential.
- Controlled diabetic subjects.

Exclusion Criteria

- Pseudohyperkalemia signs and symptoms, such as hemolyzed blood
specimen due to excessive fist clenching to make veins prominent,
difficult or traumatic venipuncture, or history of severe leukocytosis or
thrombocytosis.
- Subjects treated with lactulose, rifaximin, or other non-absorbed
antibiotics for hyperammonemia within 7 days prior to first dose of ZS on
Acute Phase Study Day 1.
- Subjects treated with sodium polystyrene sulfonate (SPS; eg,
Kayexalate®) or calcium polystyrene sulfonate (eg, Resonium®) within 3
days prior to first dose of ZS on Acute Phase Study Day 1.
- Subjects with a life expectancy of less than 12 months.
- Subjects who are severely physically or mentally incapacitated and who,
in the opinion of investigator, are unable to perform the subjects' tasks
associated with the protocol.
- Women who are pregnant, lactating, or planning to become pregnant.
- Subjects with diabetic ketoacidosis.
- Presence of any condition which, in the opinion of the investigator, places
the subject at undue risk or potentially jeopardizes the quality of the data
to be generated.
- Known hypersensitivity or previous anaphylaxis to ZS or to components
thereof.
- Treatment with a drug or device within the last 30 days that has not
received regulatory approval at the time of study entry.
- Subjects with cardiac arrhythmias that require immediate treatment.
- Subjects on dialysis.
- Subjects randomized into the previous ZS-002, ZS-003, ZS-004, or ZS-004E studies.
- Documented GFR <15 mL/min within 90 days prior to study entry.

Location

Deland, Florida, United States, 32720

Location

New Smyrna Beach, Florida, United States, 32168

Location

Orangeburg, South Carolina, United States, 29118

Location

Tempe, Arizona, United States, 85284

Location

Sumter, South Carolina, United States, 29150

Location

Paramount, California, United States, 90723

Location

Miami, Florida, United States, 33015

Location

Los Angeles, California, United States, 90022

Arms	Assigned Interventions
Experimental: Sodium Zirconium Cyclosilicate	Drug: Sodium Zirconium Cyclosilicate Acute Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) for 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) based on i-STAT potassium measurements up to 12 months. Other Name: ZS

Arms

Assigned Interventions

Experimental: Sodium Zirconium Cyclosilicate

Drug: Sodium Zirconium Cyclosilicate
Acute Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) for 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) based on i-STAT potassium measurements up to 12 months.

Other Name: ZS

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 56 sites in the Unites States, Australia, South Africa, Germany, the United Kingdom and the Netherlands from 23 June 2014 to 04 November 2016

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Subject Disposition	All Screened Subjects

Participant Flow for 2 periods

Period 1: Acute Phase: ZS 10 g TID

	Subject Disposition
STARTED	751
COMPLETED	746
NOT COMPLETED	5
Participant's Compliance	1
Hypo- or Hyperkalemia	1
Protocol Violation	1
Physician Decision	1
Withdrawal by Subject	1

Period 2: Extended Dosing Phase: ZS

	Subject Disposition
STARTED	746
COMPLETED	466
NOT COMPLETED	280
Adverse Event	51
Expected Progression of CKD	40
Hypokalemia	9
Sponsor's Decision	5
Met ECG Withdrawal Criteria	7
Withdrawal by Subject	81
Physician Decision	8
Lost to Follow-up	31
Protocol Violation	2
Death	8
Subject Compliance	17
Hyperkalemia	5
Various reasons	16

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Acute Phase: ZS

Baseline Measures

	Acute Phase: ZS
Number of Participants [units: Participants]	751
Age Continuous [units: Years] Mean ± Standard Deviation	63.6 ± 13.03
Race/Ethnicity, Customized [units: Participants]
Asian	25
Native Hawaiian or Other Pacific Islander	3
Black or African American	89
White	624
Other	10
Use of RAAS inhibitor medication [units: Participants]	527
Co-morbidities at baseline [units: Participants]
Diabetes mellitus	471
Chronic kidney disease	513
Heart Failure	285
Baseline eGFR [units: Participants]
<15	46
15-<30	243
30-<60	263
≥60	190
Missing	9
Acute Phase baseline Serum Potassium [units: Participants]
<5.5 mmol/L	287
5.5<6.0 mmol/L	338
≥6.0 mmol/L	126
Sex: Female, Male ^[1] [units: Participants]
Female	303
Male	448

Outcome Measures

1. Primary Outcome Measure: Percent of Participants with Restoration of Normal Serum Potassium (S-K) Values (3.5 to 5.0 mmol/L, Inclusive) at the End of the Acute Phase [ Time Frame: 72 Hours ]

Measure Type	Primary
Measure Name	Percent of Participants with Restoration of Normal Serum Potassium (S-K) Values (3.5 to 5.0 mmol/L, Inclusive) at the End of the Acute Phase
Measure Description	Percentage of subjects with S-K values between 3.5 and 5.0 mmol/L, inclusive at the end of the Acute Phase - ITT Population
Time Frame	72 Hours
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Intent To Treat populations for the Acute Phase (AP-ITT) included subjects who received at least one dose of ZS with at least one S-K assessment after administration of Acute Phase ZS. Efficacy: Separate analyses were performed for the Acute and Extended Dosing Phases.

Reporting Groups

	Description
Percentage	Percentage of subjects with S-K values between 3.5 and 5.0 mmol/L, inclusive at the end of the Acute Phase - ITT Population

Measured Values

	Percentage
Number of Participants Analyzed [units:participants]	748
Percent of Participants with Restoration of Normal Serum Potassium (S-K) Values (3.5 to 5.0 mmol/L, Inclusive) at the End of the Acute Phase [units: Percentage of participants] Number (95% Confidence Interval)	77.9 (74.8 to 80.9)

No statistical analysis provided for Percent of Participants with Restoration of Normal Serum Potassium (S-K) Values (3.5 to 5.0 mmol/L, Inclusive) at the End of the Acute Phase

2. Primary Outcome Measure: Percentage of Participants with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase Days 85 to 365 [ Time Frame: Study Days 85 to 365 ]

Measure Type	Primary
Measure Name	Percentage of Participants with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase Days 85 to 365
Measure Description	Percentage of subjects with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase - ITT Population
Time Frame	Study Days 85 to 365
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Extended Phase Intent To Treat populations (EP-ITT) included subjects who received at least one dose of ZS in the EP and have at least one S-K assessment after administration of Extended Phase ZS. Efficacy: Separate analyses were performed for the Acute and Extended Dosing Phases.

Reporting Groups

	Description
Percentage	Percentage of subjects with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase - ITT Population

Measured Values

	Percentage
Number of Participants Analyzed [units:participants]	646
Percentage of Participants with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase Days 85 to 365 [units: Percentage of participants] Number (95% Confidence Interval)	88.4 (85.7 to 90.8)

No statistical analysis provided for Percentage of Participants with mean S-K values ≤ 5.1 mmol/L during Extended Dosing Phase Days 85 to 365

3. Secondary Outcome Measure: Proportion of subjects with mean S-K between 3.5 and 5.5 mmol/L, inclusive months 3 to 12 [ Time Frame: Study Days 85 to 365 ]

Measure Type	Secondary
Measure Name	Proportion of subjects with mean S-K between 3.5 and 5.5 mmol/L, inclusive months 3 to 12
Measure Description	Proportion of Subjects with mean S-K between 3.5 and 5.5 mmol/L during Extended Dosing Phase - ITT Population
Time Frame	Study Days 85 to 365
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended phase ITT population

Reporting Groups

	Description
Proportion	Proportion of subjects with mean S-K between 3.5 and 5.5 mmol/L, inclusive months 3 to 12

Measured Values

	Proportion
Number of Participants Analyzed [units:participants]	646
Proportion of subjects with mean S-K between 3.5 and 5.5 mmol/L, inclusive months 3 to 12 [units: Proportion of participants] Number (95% Confidence Interval)	0.985 (0.972 to 0.993)

No statistical analysis provided for Proportion of subjects with mean S-K between 3.5 and 5.5 mmol/L, inclusive months 3 to 12

4. Secondary Outcome Measure: Mean S-K levels months 3 to 12, months 6 to 9, and months 9 to 12. [ Time Frame: Study days 85 to 365 ]

Measure Type	Secondary
Measure Name	Mean S-K levels months 3 to 12, months 6 to 9, and months 9 to 12.
Measure Description	Mean S-K levels months 3 to 12(EP Days 85, 113, 141, 176, 211, 239, 267, 295, 330, 365 and EOS),months 6 to 9, and months 9 to 12.
Time Frame	Study days 85 to 365
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Extended phase ITT population

Reporting Groups

	Description
Mean S-K levels months 3 to 12,6 to 9, and 9 to 12

Measured Values

	Mean S-K levels months 3 to 12,6 to 9, and 9 to 12
Number of Participants Analyzed [units:participants]	734
Mean S-K levels months 3 to 12, months 6 to 9, and months 9 to 12. [units: mmol/L] Mean (Standard Deviation)
Acute Phase Baseline	5.59 (0.425)
Extended Dosing Days 85 to 365/End of Study	4.66 (0.379)
Extended Dosing Days 211 to 267	4.68 (0.404)
Extended Dosing Days 295 to 365	4.62 (0.401)

No statistical analysis provided for Mean S-K levels months 3 to 12, months 6 to 9, and months 9 to 12.

Serious Adverse Events

Time Frame	One year
Additional Description	No text entered.

Reporting Groups

	Description
Acute Phase: ZS	No text entered.
Extended Dosing Phase: ZS	No text entered.

Serious Adverse Events

Acute Phase: ZS

Extended Dosing Phase: ZS

Total, serious adverse events

# participants affected / at risk

1/751 (0.13%)

161/746 (21.58%)

Musculoskeletal and connective tissue disorders

Neuropathic arthropathy¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Injury, poisoning and procedural complications

Lower limb fracture¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/751 (0.00%)

14/746 (1.88%)

# events

Cardiac disorders

Cardiac failure congestive¹,^†

# participants affected / at risk

0/751 (0.00%)

11/746 (1.47%)

# events

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure¹,^†

# participants affected / at risk

0/751 (0.00%)

5/746 (0.67%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

0/751 (0.00%)

4/746 (0.54%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

0/751 (0.00%)

7/746 (0.94%)

# events

Infections and infestations

Lobar pneumonia¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

0/751 (0.00%)

6/746 (0.80%)

# events

Metabolism and nutrition disorders

Fluid overload¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

0/751 (0.00%)

4/746 (0.54%)

# events

Gastrointestinal disorders

Ascites¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

General disorders

Pyrexia¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Angina unstable¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Investigations

Tropinin increased¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Hepatobiliary disorders

Cholecystitis¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

General disorders

Asthenia¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Cardiac disorders

Ventricular tachycardia¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Injury, poisoning and procedural complications

Ankle fracture¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Myocardial infarction¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Infections and infestations

Osteomyelitis¹,^†

# participants affected / at risk

0/751 (0.00%)

8/746 (1.07%)

# events

Skin and subcutaneous tissue disorders

Skin ulcer¹,^†

# participants affected / at risk

0/751 (0.00%)

4/746 (0.54%)

# events

Gastrointestinal disorders

Gastric ulcer¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

General disorders

Chest pain¹,^†

# participants affected / at risk

0/751 (0.00%)

11/746 (1.47%)

# events

Infections and infestations

Pneumonia cryptococcal¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Renal and urinary disorders

Renal failure chronic¹,^†

# participants affected / at risk

0/751 (0.00%)

4/746 (0.54%)

# events

Vascular disorders

Malignant hypertension¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Diverticulitis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary oedema¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Vascular disorders

Peripheral arterial occulsive disease¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

1/751 (0.13%)

4/746 (0.54%)

# events

Injury, poisoning and procedural complications

Comminuted fracture¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Metabolism and nutrition disorders

Hyperkalaemia¹,^†

# participants affected / at risk

0/751 (0.00%)

4/746 (0.54%)

# events

Infections and infestations

Abscess limb¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Musculoskeletal and connective tissue disorders

Lumbar spinal stenosis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Gastrointestinal disorders

Gastrointestinal necrosis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Social circumstances

Dependence on enabling machine or device¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Renal and urinary disorders

Renal failure acute¹,^†

# participants affected / at risk

0/751 (0.00%)

8/746 (1.07%)

# events

Renal and urinary disorders

Cystitis haemorrhagic¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Infections and infestations

Bacteraemia¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Vascular disorders

Hypertensive crisis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Gastrointestinal disorders

Peptic ulcer¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Nervous system disorders

Dysarthria¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/751 (0.00%)

5/746 (0.67%)

# events

Investigations

Electrocardiogram abnormal¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Gas gangrene¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

General disorders

Impaired healing¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Bundle branch block right¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Renal and urinary disorders

Azotaemia¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Myocarditis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Breast cancer¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Nervous system disorders

Balance disorder¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Injury, poisoning and procedural complications

Anaemia postoperative¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Respiratory, thoracic and mediastinal disorders

Sleep apnoea syndrome¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Cardiac arrest¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Injury, poisoning and procedural complications

Toxicity to various agents¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Aortic valve stenosis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Coronary artery disease¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Skin and subcutaneous tissue disorders

Diabetic foot¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Gastrointestinal disorders

Pancreatitis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

General disorders

Local swelling¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

1/751 (0.13%)

3/746 (0.40%)

# events

Infections and infestations

Appendicitis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

General disorders

Generalised oedema¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Nervous system disorders

Cerebrovascular accident¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Cardiac disorders

Cardiomyopathy¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Surgical and medical procedures

Leg amputation¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

0/751 (0.00%)

3/746 (0.40%)

# events

Nervous system disorders

Multiple sclerosis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intraductal proliferative breast lesion¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Infections and infestations

Pneumonia mycoplasmal¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Atypical pneumonia¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Nervous system disorders

Transient ischaemic attack¹,^†

# participants affected / at risk

0/751 (0.00%)

2/746 (0.27%)

# events

Renal and urinary disorders

Hydronephrosis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

751

Cardiac disorders

Palpitations¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Gangrene¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

General disorders

Necrosis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Osteomyelitis acute¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Nervous system disorders

Presyncope¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Staphylococcal sepsis¹,^†

# participants affected / at risk

1/751 (0.13%)

1/746 (0.13%)

# events

Gastrointestinal disorders

Gastrointestinal haemorrhage¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Injury, poisoning and procedural complications

Drug dose omission¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Musculoskeletal and connective tissue disorders

Chondrocalcinosis pyrophosphate¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Diabetic foot infection¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Gastrointestinal disorders

Gastritis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Injury, poisoning and procedural complications

Pelvic fracture¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Infective exacerbation of chronic obstructive airways disease¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Injury, poisoning and procedural complications

Femoral neck fracture¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Respiratory, thoracic and mediastinal disorders

Pulmonary mass¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Heart injury¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Psychiatric disorders

Delirium¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Coronary artery stenosis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Musculoskeletal and connective tissue disorders

Osteoarthritis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Pericarditis uraemic¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Escherichia urinary tract infection¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Urosepsis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Viral infection¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Metabolism and nutrition disorders

Gout¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Acute coronary syndrome¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Gastrointestinal disorders

Oesophagitis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Lower respiratory tract infection¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Right ventricular failure¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Gastrointestinal infection¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Psychiatric disorders

Panic attack¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to lung¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Cardiac failure acute¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Metabolism and nutrition disorders

Hypovolaemia¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Injury, poisoning and procedural complications

Craniocerebral injury¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Respiratory, thoracic and mediastinal disorders

Hypercapnia¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Injury, poisoning and procedural complications

Limb injury¹,^†

# participants affected / at risk

0/751 (0.00%)

1/746 (0.13%)

# events

Metabolism and nutrition disorders

Hypoglycaemia¹,^†

# participants affected / at risk

0/751 (0.00%)

4/746 (0.54%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

Other Adverse Events

Time Frame	One year
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Acute Phase: ZS	No text entered.
Extended Dosing Phase: ZS	No text entered.

Other Adverse Events

Acute Phase: ZS

Extended Dosing Phase: ZS

Total, other (not including serious) adverse events

# participants affected / at risk

11/751 (1.46%)

386/746 (51.74%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/751 (0.00%)

42/746 (5.63%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

1/751 (0.13%)

78/746 (10.46%)

General disorders

Oedema peripheral¹,^†

# participants affected / at risk

1/751 (0.13%)

72/746 (9.65%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

4/751 (0.53%)

56/746 (7.51%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

2/751 (0.27%)

46/746 (6.17%)

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

3/751 (0.40%)

55/746 (7.37%)

Infections and infestations

Upper respiratory infection¹,^†

# participants affected / at risk

0/751 (0.00%)

37/746 (4.96%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	AstraZeneca Clinical Study Information Center
Organization:	ZS Pharma, Inc
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

Henrik Rasmussen

443-699-5230

hrasmussen@zspharma.com

Investigators

Principal Investigator

Henrik Rasmussen

ZS Pharma, Inc.

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Trial Results Summaries