Overview
A Study to Evaluate the Effect of Sodium Zirconium Cyclosilicate on Chronic Kidney Disease (CKD) Progression in Participants With CKD and Hyperkalaemia or at Risk of Hyperkalaemia
Status:
Recruiting
Recruiting
Trial end date:
2025-01-15
2025-01-15
Target enrollment:
0
0
Participant gender:
All
All
Summary
The purpose of this study is to evaluate the effect of Sodium Zirconium Cyclosilicate (SZC), as adjunct to ACEi/ARB therapy (lisinopril or valsartan), on slowing CKD progression (assessed as the reduction in participant's glomerular filtration rate [eGFR] decline over time) in participants with hyperkalaemia or at high risk of hyperkalaemia.Phase:
Phase 3Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
AstraZenecaTreatments:
Irbesartan
Lisinopril
Valsartan
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 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 and ≤ 59 mL/min/1.73m2 as calculated by central laboratory
(CKD-EPI formula) at screening (Visit 1)
- Must have UACR ≥ 200 and ≤ 5000 mg/g as calculated by central laboratory at screening
(Visit 1)
- Any of the following criteria, a or b, at screening (Visit 1):
1. Cohort A: Hyperkalaemia (S-K > 5.0 to ≤ 6.5 mmol/L) as measured by the central
laboratory, and on adequate* or limited** RAASi therapy due to hyperkalaemia.
2. Cohort B: Normokalaemia (S-K ≥ 3.5 to ≤ 5.0 mmol/L) 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 to ≤ 5.0 mmol/L.
(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 treatment, the dose must have been stable for 3 months prior to
screening (Visit 1).
- Participants must be one-year postmenopausal, surgically sterile, or using one highly
effective form of birth control (defined as one that can achieve a failure rate of
less than 1% per year when used consistently and correctly). They should have been
stable on their chosen method of birth control for a minimum of one month prior to
screening (Visit 1) and willing to remain on the birth control until one month after
the last dose of study intervention.
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 diastolic blood pressure ≥ 95 mmHg (confirmed by
repeated measurement), within 2 weeks prior to screening (Visit 1). Participants may
be rescreened once blood pressure is controlled.
- QTcF > 550 msec 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
successfully treated basal cell or treated squamous cell carcinoma.
- S-K > 6.5 or < 3.5 mmol/L by local laboratory within 1 day prior to the scheduled
first dose of SZC in the initiation phase.
- Evidence of COVID-19 infection within 2 weeks prior to screening (Visit 1).
- Treated with dual blockade of RAAS (combined use of an ACEi and ARB) within 3 months
prior to screening (Visit 1).
- Treated with an angiotensin receptor neprilysin inhibitor (ARNI; sacubitril/valsartan
[Entresto®]) within 3 months prior to screening (Visit 1).
- Treated with an MRA within 3 months prior to screening (Visit 1).
- Treated with aliskiren-containing products with 3 months prior to screening (Visit 1).
- Treated with SPS (eg, Kayexalate, Resonium), CPS (Resonium Calcium), patiromer
(Veltassa®), or SZC (Lokelma®) within 7 days prior to screening (Visit 1).
- Participation in another clinical study with an investigational product administered
within one month prior to screening (Visit 1).
- Not willing or not able to change to lisinopril or valsartan/irbesartan, the
protocol-mandated RAASi study intervention.
- Previous dosing with SZC in the present study.
- Currently pregnant (confirmed with positive pregnancy test at screening [Visit 1]) or
breastfeeding.
- Judgment by the investigator that the participant is unlikely to comply with study
procedures, restrictions, and requirements.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).