Please select the eligibility criteria that correspond to the clinical trial below.
Title: Multicenter, Two-phase, Multi-dose, Prospective, Randomized, Double-blind, Placebo-Controlled Study of Safety and Efficacy of Microporous, Fractionated, Protonated Zirconium Silicate in Mild to Moderate Hyperkalemia
Brief Summary: Acute Phase: It is hypothesized that ZS (zirconium silicate) is more effective than placebo control (alternative hypothesis) in lowering S-K levels in subjects with S-K between 5.0 - 6.5 mmol/l versus no difference between ZS and placebo control (null hypothesis).

Subacute Phase (randomized withdrawal): It is hypothesized that ZS once daily is more effective than placebo control (alternative hypotheses) in maintaining normokalemic levels (3.5 - 4.9 mmol/l) among subjects completing the Acute Phase versus no difference between each ZS dose and respective placebo controls (null hypotheses).


Options:
A: Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female or male aged ≥ 18 years at screening Visit 1. For patients aged \<20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
3. Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of endstage renal disease (ESRD) for at least 3 months before randomization.
4. Patients must have hemodialysis access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study.
5. Pre-dialysis serum K \>5.4 mmol/L after long inter-dialytic interval and \>5.0 mmol/L after one short inter-dialytic interval during screening (as assessed by central lab).
6. Prescribed dialysate K concentration ≤ 3 mmol/L during screening
7. Sustained Qb ≥200 ml/min and spKt/V ≥1.2 (or URR ≥ 63) on stable hemodialysis/hemodiafltration prescription during screening with prescription (time, dialyzer, blood flow \[Qb\], dialysate flow rate \[Qd\] and bicarbonate concentration) expected to remain unchanged during study
8. Heparin dose (if used) must be stable during screening and expected to be stable during the study
9. Subjects must be receiving dietary counseling appropriate for ESRD patients treated with hemodialysis/hemodiafiltration as per local guidelines, which includes dietary potassium restriction.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca, including ZS Pharma staff and/or staff at the study site)
2. Hemoglobin \<9 g/dL on screening (as assessed on Visit 1)
3. Lack of compliance with hemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required)
4. Patients treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7 days before screening or anticipated in requiring any of these agents during the study
5. Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 12 weeks prior to randomization
6. Laboratory diagnosis of hypokalemia (K \< 3.5 mmol/L), hypocalcemia (Ca \< 8.2 mg/dL; for Japan hypocalcemia is defined as albumin-corrected Ca \< 8.0 mg/dL), hypomagnesemia (Mg \< 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization
7. Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).
8. Severe leukocytosis (\>20× 10\^9/L) or thrombocytosis (≥450 × 10\^9/L) during screening
9. Polycythemia (Hb \>14 g/dL) during screening
10. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization
11. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug
12. Patients unable to take oral ZS drug mix
13. Scheduled date for living donor kidney transplant
14. Patients with a life expectancy of less than 6 months
15. Female patients who are pregnant or breastfeeding
16. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
17. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
18. Participation in another clinical study with an investigational product during the last 1 month before screening
19. Any medical condition, including active, clinically significant infection, that in the opinion of the investigator or Sponsor may pose a safety risk to a patient in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation
20. Presence of cardiac arrhythmias or conduction defects that require immediate treatment
21. History of alcohol or drug abuse within 2 years prior to randomization
22. Previous randomization in the present study
B: Inclusion Criteria:

* Age ≥ 18 years
* Taking at least three medications for blood pressure (one a diuretic)
* Uncontrolled high blood pressure
* Abnormal kidney function (with-eGFR, a measure of kidney function, of 25 - ≤ 45 mL/min/1.73m2
* Normal Blood serum Potassium in a specific range (4.3 - 5.1 mEq/L)

Exclusion Criteria:

* History of untreated known causes of high blood pressure, excluding kidney disease (not CKD)
* Inability to measure BP
* Not taking high blood pressure medications as prescribed medications
* Recent change in renal function (in the past 3 months) which has required hospitalization or dialysis
* Renal transplant
* History of cancer within past 12 months
* Recent cardiovascular event with last 3 months
* Clinically significant abnormalities of heart rhythm (ventricular arrhythmia or atrial fibrillation with uncontrolled heart rate)
* Inability to take study medication
* Alcoholism
C: Inclusion Criteria:

* Provision of written informed consent.
* Over 18 years of age.
* Mean i-STAT potassium values between 5.0 - 6.5 mmol/l inclusive, at screening (Study Day 0).
* Ability to have repeated blood draws or effective venous catheterization.
* Women of childbearing potential must be practicing a highly effective method of birth control.

Exclusion Criteria:

* Pseudohyperkalemia signs and symptoms, such as excessive fist clinching hemolyzed blood specimen, severe leukocytosis or thrombocytosis.
* Subjects treated with lactulose, xifaxan or other nonabsorbed antibiotics for hyperammonemia within the last 7 days.
* Subjects treated with resins (such as Sevelamer acetate or Sodium polystyrene sulfonate \[SPS; e.g. Kayexalate®\]), calcium acetate, calcium carbonate, or lanthanum carbonate, within the last 7 days.
* Subjects with a life expectancy of less than 3 months.
* Subjects who are HIV positive.
* 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 Ketoacidosis/Acidemia.
* 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.
* Previous treatment with ZS
* 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.
* Insulin-dependent diabetes mellitus
* 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