Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2/3 Multicenter, Dose-response Study to Assess Efficacy and Safety of ZS (Sodium Zirconium Cyclosilicate), in Japanese Patients With Hyperkalemia
Brief Summary: To assess efficacy of 5 g three times daily (TID) and 10 g TID ZS versus placebo in Japanese patients with hyperkalemia (serum potassium \[S-K\] ≥ 5.1 mmol/L and ≤ 6.5 mmol/L).


Options:
A: Inclusion Criteria:

1. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
2. Subject must be ≥ 18 years of age inclusive, at the time of signing the informed consent form.
3. Subjects must have haemodialysis access consisting of an arteriovenous fistula, AV graft, or tunnelled (permanent) catheter which is expected to remain in place for the entire duration of the study.
4. Receiving haemodialysis (or hemodiafiltration) 3 times a week for treatment of end-stage renal disease (ESRD) for at least 3 months before randomization.
5. Pre-dialysis S-K \> 5.4 mmol/L after long inter-dialytic interval and \> 5.0 mmol/L after at least 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 haemodialysis / haemodiafltration prescription during screening with prescription (time, dialyzer, blood flow \[Qb\], dialysate flow rate \[Qd\] and bicarbonate concentration) expected to remain unchanged during study.
8. Subjects must be receiving dietary counselling appropriate for ESRD subjects treated with haemodialysis / haemodiafiltration as per local guidelines, which includes dietary potassium restriction.

Exclusion Criteria:

1. 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.
2. Pseudohyperkalaemia secondary to haemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).
3. Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization.
4. Presence of cardiac arrhythmias or conduction defects that require immediate treatment.
5. Any medical condition, including active, clinically significant infection or liver disease, that in the opinion of the investigator or Sponsor may pose a safety risk to a subject in this study, which may confound safety or efficacy assessment and jeopardize the quality of the data, or may interfere with study participation.
6. History of QT prolongation associated with other medications that required discontinuation of that medication; congenital long QT syndrome or QTc(f) \> 550 msec; uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication or with transient atrial fibrillation associated with dialysis or peridialytic period are permitted.
7. Subjects treated with sodium polystyrene sulfonate (e.g. 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.
8. Participation in another clinical study with an investigational product administered in the last 1 month before screening.
9. Haemoglobin \< 9 g/dL on screening (as assessed on Visit 1).
10. Laboratory diagnosis of hypokalaemia (K \< 3.5 mmol/L), hypocalcemia (Ca \< 8.2 mg/d or albumin-corrected Ca \< 8.0 mg/dL if the latter is used in local practice), hypomagnesemia (Mg \< 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization.
11. Severe leukocytosis (\> 20 × 109/L) or thrombocytosis (≥ 450 × 109/L) during screening.
12. Polycythaemia (Hb \> 14 g/dL) during screening.
13. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
14. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
15. Previous randomisation in the present study.
16. For women only - currently pregnant (confirmed with positive pregnancy test or uterine ultrasound if pregnancy test is questionable) or breast-feeding.
17. Females of childbearing potential, unless using contraception as detailed in the protocol or sexual abstinence.
18. Lack of compliance with haemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required).
19. Subjects unable to take investigational product drug mix.
20. Scheduled date for living donor kidney transplant.
21. Subjects with a life expectancy of less than 6 months.
22. Known hypersensitivity or previous anaphylaxis to SZC or to components thereof.
23. History of alcohol or drug abuse within 2 years prior to randomization.
B: 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.
C: 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
D: Inclusion Criteria:

* Provision of informed consent prior to any study specific procedures.
* Patients aged ≥18. For patients aged \<20 years, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
* Two consecutive i-STAT potassium values, measured 60 (± 10) minutes apart, both values should be ≥ 5.1 mmol/L and ≤ 6.5 mmol/L and measured within 1 day before the first dose of study drug on Study Day 1.
* Ability to have repeated blood draws or effective venous catheterization.
* Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.

Exclusion Criteria:

* Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
* Cause or symptoms of pseudohyperkalemia, such as

  1. hemolyzed blood specimen due to excessive fist clenching to make veins prominent
  2. hemolyzed blood specimen due to difficult or traumatic venepuncture
  3. history of severe leukocytosis or thrombocytosis
* Patients treated with lactulose, rifaximin, or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of study drug on Study Day 1
* Patients treated with resins (such as sevelamer hydrochloride, sodium polystyrene sulfonate \[SPS; e.g. Kayexalate®\] or calcium polystyrene sulfonate \[CPS\]), calcium acetate, calcium carbonate, or lanthanum carbonate, within 7 days prior to the first dose of study drug
* Patients with a life expectancy of less than 3 months
* Patients who are severely physically or mentally incapacitated and who, in the opinion of investigator, are unable to perform the patients' tasks associated with the protocol
* Female patients who are pregnant, lactating, or planning to become pregnant
* Patients who have an active or history of diabetic ketoacidosis
* Presence of any condition which, in the opinion of the investigator, places the patient 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
* Patients with cardiac arrhythmias that require immediate treatment
* Patients on dialysis

Answer: D