Chronic Kidney disease, Hyperkalemia
Conditions
Interventions
- initiation phase: initial dose of SZC will be administered. No changes will be made to the ACEi or ARB therapy at this stage
- run-in phase: open-label SZC and either lisinopril or valsartan
- mai
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and protocol - Must be 18 years of age or more at the time of signing the informed consent. For participants < 20 years of age and enrolled in Japan, a written informed consent should be obtained from the participant and his or her legally acceptable representative - Must have eGFR 25 or more and 59 mL/min/1.73m2 or less as calculated by central laboratory (CKD-EPI formula) at screening (Visit 1) - Must have UACR 200 or more and 5000 mg/g or less as calculated by central laboratory at screening (Visit 1). If the first sample does not fulfil eligibility criteria, a second sample can be obtained during the screening period; if so, the UACR measurement from the second sample must be within the eligibility range. - Any of the following criteria, a or b, at screening (Visit 1): 1. Cohort A: Hyperkalaemia (S-K 5.0 or more to 6.5 mmol/L or less ) as measured by the central laboratory, and on adequate* or limited** RAASi therapy due to hyperkalaemia. 2. Cohort B: Normokalaemia (S-K 3.5 or more to 5.0 mmol/L or less ) as measured by the central laboratory and on limited** RAASi therapy due to high risk of hyperkalaemia. High risk of hyperkalaemia is defined as: (i) Participants with a previous medical history or record of hyperkalaemia within the prior 24 months, who are on limited** RAASi therapy despite indication in CKD. (ii) Participants in whom RAASi therapy is indicated in CKD, who are on limited** RAASi therapy and have S-K 4.7 or more to 5.0 mmol/L or less. (iii) Participants in whom RAASi therapy has been discontinued or reduced to suboptimal* doses because of hyperkalaemia. *Adequate RAASi dose levels are defined in protocol; doses lower than these are considered as suboptimal. **Limited RAASi therapy is defined as no or suboptimal RAASi therapy according to dosing guidance provided in protocol. - If on thiazide or loop diuretics, the dose must have been stable for 2 weeks prior to screening (Visit 1). - If on RAASi therapy, the dose must have been stable for one month prior to screening (Visit 1) and remain stable during screening. - If on an SGLT2i inhibitor (ie, dapagliflozin and canagliflozin), finerenone, or any other medications in these 2 classes that are approved f
Exclusion criteria
Exclusion criteria: - New York Heart Association class III to IV congestive heart failure at the time of screening (Visit 1) or previous history of severe or symptomatic heart failure. - Myocardial infarction, unstable angina, stroke, or transient ischaemic attack within 3 months prior to screening (Visit 1). - Systolic blood pressure 160 mmHg or more or diastolic blood pressure 95 mmHg or less (confirmed by repeated measurement), within 2 weeks prior to screening (Visit 1). Participants may be rescreened once blood pressure is controlled. - QTcF 550 msec or more at screening (Visit 1). - History of QT prolongation associated with other medications that required discontinuation of that medication. - Congenital long QT syndrome. - Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation and heart rate controlled by medication are permitted. - Type 1 diabetes mellitus. - Lupus nephritis or anti neutrophil cytoplasmic antibody-associated vasculitis. - Change in renal function requiring hospitalisation or dialysis within 3 months prior to screening (Visit 1). - History of renal transplant (or anticipated need for renal transplant during the study). - Severe hepatic impairment, biliary cirrhosis, or cholestasis. - History of hereditary or idiopathic angioedema. - Any prior hypersensitivity to ACEi or ARB that in the investigator's judgment precludes use of lisinopril and valsartan/irbesartan. Prior hypersensitivity reactions to consider include, but are not limited to, development of angioedema, icterus, hepatitis, or neutropaenia or thrombocytopaenia requiring treatment modification. - Known hypersensitivity or previous anaphylaxis to SZC or to components thereof. - Any condition outside the CV and renal disease area such as, but not limited to, malignancy, with a life expectancy of less than 2 years based on investigator's clinical judgment. - Active malignancy requiring treatment at the time of screening (Visit 1), except for suc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Total eGFR slope and Chronic eGFR slope [ Time Frame: Total slope: from randomisation visit to the end of the maintenance phase at Week 104; Chronic slope: from Week 12 visit to the end of the maintenance phase at Week 104 ] | — |
Countries
Argentina, Brazil, Bulgaria, Canada, China, India, Italy, Japan, Malaysia, Mexico, Philippines, Poland, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United States of America, Vietnam
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed