Please select the eligibility criteria that correspond to the clinical trial below.
Title: Multicenter, Multi-phase, Multi-dose, Prospective, Double-blind, Placebo-controlled, Maintenance Study of Safety and Efficacy of ZS (Microporous, Fractionated, Protonated Zirconium Silicate) in Hyperkalemia.
Brief Summary: It is hypothesized that ZS is more effective than placebo control (alternative hypothesis) in maintaining mean double-blind randomized maintenance phase (DBRMP) Day 8-29 serum potassium levels (3.5 - 5.0 mmol/l, inclusive) among hyperkalemic subjects in whom normokalemia was established during the open-label acute phase versus no difference between each ZS dose (highest to lowest) versus placebo control (null hypothesis).


Options:
A: Inclusion Criteria:

* Males and females ages 18 - 80
* Chronic kidney disease (CKD) - eGFR 15 to \< 60 mL/min/1.73m2 at screening
* Hyperkalemia, defined as a serum potassium value of 5.1 to \< 6.5 mEq/L at screening
* Taking either an Angiotensin-Converting Enzyme (ACE) Inhibitor, an Angiotensin II receptor blocker (ARB), or an aldosterone antagonist (AA) medication
* Informed consent given

Exclusion Criteria:

* Participants with auto-immune related chronic kidney disease such as lupus nephritis or renal scleroderma/scleroderma renal crisis, or mixed connective tissue disease with renal involvement
* Participants with uncontrolled Type 1 diabetes, defined as or a HbA1c \> 10.0 %, or hospitalization to treat hyper- or hypo-glycemia in the past 3 months within the previous 6 months in participants with Type 2 diabetes
* Participants with severe heart failure, defined as NYHA (New York Heart Association) class IV
* Participants with major surgery including thoracic and cardiac, in the past 3 months, or participants with heart or kidney transplant
* Participants with significant cardiovascular or cerebrovascular events in the past 2 months, such as cardiac arrest, myocardial infarction, or stroke
* Participants with BMI ≥ 40 kg/m2
B: Inclusion Criteria:

* Aged 18 years and over
* Outpatients followed at the pre-dialysis or nephrology clinics of Maisonneuve-Rosemont Hospital
* Subjects who have taken SPS in the past 7 days: serum potassium level measured for their regular followup of 4.5 to 5.5 mmol/L, inclusive, and serum potassium level of 5.0 to 5.9 mmol/L, inclusive, after a one week washout period
* Subjects who have not taken SPS in the past 7 days: serum potassium levels measured for their regular followup and on the day of randomisation of 5.0 to 5.9, inclusive

Exclusion Criteria:

* Subjects with a contraindication to SPS : known hypersensitivity to the product, history of obstructive bowel disease, patients at high risk of obstructive bowel disease
* Subjects unable of giving informed consent
* Subjects with severe or symptomatic hyperkalemia requiring a treatment
* Subjects on dialysis (hemodialysis or peritoneal dialysis)
* Women who are pregnant or breastfeeding
* Subjects who have had a change in the dosage of insulin in the past week, if this change represents more than 10% of the daily total dose or more than 5 units
* Subjects who stopped, started or changed the dosage of an angiotensin converting enzyme inhibitor, an angiotensin II receptor blocker or aliskiren in the past 60 days
* Subjects who stopped, started or changed the dosage of another medication affecting serum potassium levels in the past 30 days
* Subjects who have had an episode of decompensated heart failure in the past 30 days
* Subjects currently enrolled on another research protocol
* Subjects who are lactose intolerant
C: Inclusion Criteria:

* Provision of written informed consent.
* Over 18 years of age.
* Two consecutive i-STAT potassium values, measured 60-minutes apart, both ≥5.1 mmol/l and measured within 1 day of the first ZS dose on AP Study Day 1.
* Ability to have repeated blood draws or effective venous catheterization.
* Women of childbearing potential must be using two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at AP Study Day 1. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential.

Exclusion Criteria:

* Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen, history of severe leukocytosis or thrombocytosis.
* Subjects treated with lactulose, Xifaxan or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug.
* Subjects treated with resins (such as sevelamer acetate or sodium polystyrene sulfonate \[SPS; e.g. Kayexalate®\]), calcium acetate, calcium carbonate, or lanthanum carbonate, within 7 days prior to the first dose of study drug.
* Subjects with a life expectancy of less than 3 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.
* Randomization into the previous ZS-002 or ZS-003 studies.
* 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.
D: Key Inclusion Criteria:

* Potassium concentration \> 5.0 mEq/L from two blood draws at Screening
* Stable RAASi medication, if taking
* Medications taken on a chronic basis are given once daily or twice daily
* Informed consent given

Key Exclusion Criteria:

* Expected need for dialysis
* Major organ transplant
* History of conditions associated with pseudohyperkalemia
* History of swallowing disorder, gastroparesis, bariatric surgery, bowel obstruction or severe gastrointestinal disorders or major gastrointestinal surgery
* Cancer or unstable medical condition

Answer: C