Continuing Sodium Zirconium Cyclosilicate (SZC) after discharge study - CONTINUITY

This is an open-label, randomised study in participants with chronic kidney disease (CKD) treated for hyperkalaemia (HK) whilst in hospital. The study will compare SZC to standard of care (SoC) with the goal of determining: • If continued use of SZC maintains normokalaemia (NK) better than SoC after participant discharge from the hospital. • If continued use of SZC after discharge will reduce HK related healthcare resource utilisation compared to SoC.

This is a Phase 4, randomised, controlled, open-label, parallel-group, multicentre study in participants with CKD treated for HK whilst in hospital. • Participants from 30 to 50 sites in 4 to 7 countries will be screened for enrolment. In total, 632 participants will be screened to yield 506 participants entering the inpatient phase, resulting in 430 participants discharged and randomised (215 per arm) and 344 evaluable participants. • The study plans to enrol approximately equal numbers of participants with mild HK (K+ between > 5.0 and ≤ 5.5 mmol/L) and with moderate/severe HK (K+ between > 5.5 and ≤ 6.5 mmol/L), with a minimum of 30% of the enrolled participants in either group. • During the in-hospital phase, participants will be treated with SZC as per local label, starting at baseline and based on local K+ measurement obtained within 24 hours of treatment initiation:). - Participants treated with a K-binder other than SZC, at ED visit/hospital admission will be switched to correction treatment with SZC if they are still HK. Such a therapy modification must be based on the investigator’s medical judgement of the participant’s best interest. - Participants who received any K-binder, including SZC at ED visit/hospital admission and are NK at baseline can directly start the maintenance dose of SZC. - Participants who initiated SZC during ED visit/hospital admission and are still HK will continue on SZC correction dose (up to 72 hours). - All other participants will start correction treatment with SZC as per local label. • At discharge, NK participants who have been treated with SZC for between 2 and 21 days whilst in hospital and are established on SZC maintenance dose will be randomised in a 1:1 ratio to one of the following arms: - Arm A: Participants discharged with SZC, as per local label, to manage HK until the end of the outpatient phase - Arm B: Participants discharged with SoC, as per local practice, to manage HK until the end of study. Note: Participants intended to be discharged with a K+ binder (as per the site routine medical practice) will not be randomised and will be discontinued from the study. Still, participants randomised into Arm B may have a K-binder prescribed at, or after Day 7 post-discharge, to treat confirmed HK or in case there is an increase in K+ level since discharge that, in the investigator’s opinion, requires therapy. • The total duration of the study for each participant will be up to approximately 189 days, with a maximum of 208 days. • Study visit schedule is as follows: In-hospital phase: - The screening visit will occur while the participant is at the hospital (up to 21 days before discharge; medical monitor’s approval may be sought for allowing longer duration hospital stays for specific participants) in order to check eligibility criteria - Inpatient phase: o The baseline visit (can occur the same day as the screening visit) where correction treatment with SZC will be initiated o The discharge visit, 1 to 20 days after baseline; medical monitor’s approval may be sought for allowing longer duration hospital stays for specific participants). Randomisation will occur at day of discharge. - Outpatient phase: - Visits will occur at 7, 30, 60, 90, 120, 150, and 180 (EOT, End of Trial) days after randomisation. Only visits at 7, 90 and 180 days after randomisation will be on-site visits, the remaining being telephone visits. If dose titration occurs at any time during the outpatient phase, unscheduled dispensation visits will be performed. Follow-up phase: - A follow-up on-site visit (end of study visit) will occur approximately 7 days after EOT. • Data will be collected at on-site visits, via telephone visits and medical chart reviews. • An adjudication committee will be involved in the study.