Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Effect of Food: An Open-Label, Randomized, Parallel Group Phase 4 Study of the Efficacy and Safety of Patiromer for Oral Suspension With or Without Food for the Treatment of Hyperkalemia (TOURMALINE)
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of patiromer administered once daily (QD) when given with food compared to without food (experimental treatment group) for the treatment of hyperkalemia (high potassium in the blood).


Options:
A: Inclusion Criteria:

* Provision of written informed consent.
* Over 18 years of age.
* GFR between 40-60 ml/min as estimated by the CKD-EPI equation. After screening two additional GFR values of between 40-60ml/min must be repeated within 24 hours before inclusion is allowed.
* S-K between 5.0 - 6.0 mmol/l (inclusive) during Study Day 0.
* Ability to have repeated blood draws or effective venous catheterization.
* Women of child bearing potential must be practicing a highly effective method of birth control.

Exclusion Criteria:

* Pseudohyperkalemia such as excessive fist clinching hemolyzed blood specimen, severe leukocytosis or thrombocytosis.
* Subjects treated with lactulose, xifaxan or other non-absorbed antibiotics for hyperammonemia within the last 7 days.
* Subjects treated with resins (such as sevelamer acetate, calcium acetate or calcium carbonate, lanthanum carbonate, Sodium polystyrene sulfonate (SPS; e.g. Kayexalate®) 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.
* Cancer within the last 5 years (other than successfully treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or early stage prostate cancer).
* 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 Zirconium Silicate or to components thereof.
* Subjects who have cardiac arrhythmias that require immediate treatment.
* Subjects with ECG changes associated with hyperkalemia.
* Subjects with acute kidney injury.
B: 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
C: 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.
D: 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

Answer: B