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Subjects who completed the Double-blind Randomized Maintenance Phase (DBRMP) Study Day 29 visit in ZS-004 (NCT 02088073) and have an i-STAT potassium value that is 3.5 to 6.2 mmol/l inclusive or who discontinued during ZS-004 due to hypo- or hyperkalemia in the DBRMP and have a mean i-STAT potassium value from two consecutive measurements at 0 and 60 minutes on Acute Phase Day 1/Maintenance Phase Day 1 that is 3.5 to 6.2 mmol/l inclusive may have the option to participate in ZS-004E (NCT 021070920). Subjects who discontinued from study ZS-004 due to any other reasons (e.g. adverse events, poor compliance, investigator decision) will not be entered into study ZS-004E. All subjects who continue into the extension study must begin dosing within two (2) days after the last dose of investigational product in ZS-004.
All subjects with i-STAT potassium values between 3.5-5.5 mmol/l, inclusive at the ZS-004 (NCT 02088073) DBRMP Study Day 29 visit, who continue directly into the open-label extension study ZS-004E (NCT 021070920), will enter the Maintenance Phase (MP) and start on open-label ZS at a dose of 10g qd. All subjects with i-STAT potassium values > 5.5 mmol/l at the ZS-004 DBRMP Study Day 29 visit will undergo an acute treatment phase (AP) where they will receive ZS 10g three times a day (tid) for 24 (3 doses) or 48 hours (6 doses). If the subject's i-STAT potassium is between 3.5-5.0 mmol/l, inclusive after 24 (AP Study Day 2) or 48 hours (AP Study Day 3), the subject will enter the MP at a starting dose of 10g qd.
For subjects who discontinued during ZS-004 DBRMP due to hypo- or hyperkalemia baseline potassium values will be determined within 1 day of administration of the first dose in the ZS-004E extension study by taking two (2) consecutive i-STAT potassium measurements at 0 and 60 minutes (± 10 minutes). If the mean i-STAT value is between 3.5 - 5.5 mmol/l, inclusive, the subject will enter directly into the MP and receive 10g ZS qd; if the mean i-STAT potassium value is > 5.5 mmol/l, the subject will enter the AP. If i-STAT potassium values are still >5.0 mmol/l on the morning of AP Study Day 3, subjects will not enter the MP but will be referred to their normal health care provider for standard of care.
If the i-STAT potassium value increases above 5.5 mmol/l during the MP with treatment at 10g qd, the dose can be increased to15g qd. Conversely, if S-K decreases to between 3.0-3.4 mmol/l, inclusive, the dose of ZS can be decreased in 5g qd, decrements. If a subject is on a 5g qd dose and still develops blood potassium i-STAT values between 3.0 - 3.4mmol, inclusive the dose can be reduced to 5g every other day.
Subjects will receive up to 11 months of treatment with open-label ZS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sodium Zirconium Cyclosilicate | Experimental | Open label oral administration of sodium zirconium cyclosilicate 10g once daily for 11 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium Zirconium Cyclosilicate | Drug | Oral 10g once daily with breakfast for 11 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L | The proportions of subjects with average serum potassium (S-K) values ≤ 5.1 mmol/L during Extended Dosing Study Days 8 to 337, inclusive | 11 months |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L | The proportions of subjects with average S-K values ≤ 5.5 mmol/L during Extended Dosing Study Days 8 to 337, inclusive | 11 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Henrik Rasmussen, MD, PhD | ZS Pharma, Inc. | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anniston | Alabama | 36207 | United States | |||
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Huntsville |
| Alabama |
| 35801 |
| United States |
| Scottsboro | Alabama | 35768 | United States |
| Phoenix | Arizona | 85027 | United States |
| Tempe | Arizona | 85284 | United States |
| Hawaiian Gardens | California | 90716 | United States |
| Los Angeles | California | 90022 | United States |
| Paramount | California | 90723 | United States |
| Riverside | California | 92505 | United States |
| Atlantis | Florida | 33462 | United States |
| Bradenton | Florida | 34208 | United States |
| Brandon | Florida | 33511 | United States |
| Brooksville | Florida | 34601 | United States |
| DeLand | Florida | 32720 | United States |
| Edgewater | Florida | 32132 | United States |
| Miami | Florida | 33015 | United States |
| Miami | Florida | 33125 | United States |
| Miami Lakes | Florida | 33014 | United States |
| Miami Lakes | Florida | 33018 | United States |
| New Smyrna Beach | Florida | 32168 | United States |
| Ocala | Florida | 34471 | United States |
| Summerfield | Florida | 34491 | United States |
| Tampa | Florida | 33607 | United States |
| Tampa | Florida | 33614 | United States |
| Winter Park | Florida | 32789 | United States |
| Columbus | Georgia | 31901 | United States |
| Decatur | Georgia | 30030 | United States |
| Evergreen Park | Illinois | 60805 | United States |
| Joliet | Illinois | 60435 | United States |
| Shreveport | Louisiana | 71101 | United States |
| Auburn | Maine | 04210 | United States |
| Chesterfield | Michigan | 48047 | United States |
| Kansas City | Missouri | 64411 | United States |
| Las Vegas | Nevada | 89115 | United States |
| Flushing | New York | 11355 | United States |
| Altoona | Pennsylvania | 16602 | United States |
| Providence | Rhode Island | 02903 | United States |
| Orangeburg | South Carolina | 29118 | United States |
| Sumter | South Carolina | 29150 | United States |
| Chattanooga | Tennessee | 37408 | United States |
| San Antonio | Texas | 78229 | United States |
| Gosford | New South Wales | Australia |
| Woolloongabba | Queensland | Australia |
| Heidelberg | Victoria | Australia |
| Melbourne | Victoria | Australia |
| Parkville | Victoria | Australia |
| Meyerspark | South Africa |
| Port Elizabeth | South Africa |
| Somerset West | South Africa |
| COMPLETED |
|
| NOT COMPLETED |
|
|
2 subjects did not have any S-K measurements during the ED phase due to early termination and are excluded from baseline characteristics
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| ID | Title | Description |
|---|---|---|
| BG000 | Extended Dosing Phase: ZS (Sodium Zirconium Cyclosilicate) QD | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| |||||||||||||||||||||||
| Study ZS-004 Acute Phase S-K baseline | Acute Phase S-K baseline of participants in Study ZS-004 | Count of Participants | Participants |
| ||||||||||||||||||||||
| Acute Phase eGFR at baseline | Acute Phase baseline from Study ZS-004 | Count of Participants | Participants |
| ||||||||||||||||||||||
| Cormordid conditions and concomitant medications which may contirubute to hyperkalemia | Categories are not mutually exclusive | Number | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Proportion of Subjects With Average Serum Potassium Values ≤ 5.1 mmol/L | The proportions of subjects with average serum potassium (S-K) values ≤ 5.1 mmol/L during Extended Dosing Study Days 8 to 337, inclusive | 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. | Posted | Number | 95% Confidence Interval | Proportion of Participants | 11 months |
|
|
| |||||||||||||||||||||||||||
| Secondary | Proportion of Subjects With Average Serum Potassium Values ≤ 5.5 mmol/L | The proportions of subjects with average S-K values ≤ 5.5 mmol/L during Extended Dosing Study Days 8 to 337, inclusive | 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. | Posted | Number | 95% Confidence Interval | Proportion of Participants | 11 months |
|
|
Eleven months
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ZS (Sodium Zirconium Cyclosilicate) QD Extended Phase Dosing | 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. | 24 | 123 | 82 | 123 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Retinal artery occlusion | Eye disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Gastritis haemorrhagic | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Diabetic foot infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Gangrene | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Lobar pneumonia | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Morganella infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Patella fracture | Injury, poisoning and procedural complications | MedDRA 17.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Adenocarcinoma of colon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dry gangrene | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA 17.0 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hyperlipidemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Dizzines | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 17.0 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| AstraZeneca Clinical Study Information Center | ZS Pharma, Inc. | 1-877-240-9479 | information.center@astrazeneca.com |
| ID | Term |
|---|---|
| D006947 | Hyperkalemia |
| ID | Term |
|---|---|
| D014883 | Water-Electrolyte Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C000597310 | sodium zirconium cyclosilicate |
Not provided
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| White |
|
| Other |
|
| ≥ 6.0 mmol/L |
|
| Chronic kidney disease |
|
| Heart failure |
|
|
| ED Study Day 22 |
|
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| ED Study Day 29 |
|
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| ED Study Day 36 |
|
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| ED Study Day 43 |
|
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| ED Study Day 50 |
|
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| ED Study Day 57 |
|
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| ED Study Day 85 |
|
|
| ED Study Day 113 |
|
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| ED Study Day 141 |
|
|
| ED Study Day 169 |
|
|
| ED Study Day 197 |
|
|
| ED Day Study 225 |
|
|
| ED Study Day 253 |
|
|
| ED Study Day 281 |
|
|
| ED Study Day 309 |
|
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| ED Study Day 337 |
|
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| ED Study Day 337/Exit |
|
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| ED Study Days 8-337 Average |
|
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|