JRCT ID: jRCT2031210441
Registered date:22/11/2021
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
Basic Information
Recruitment status | Not Recruiting |
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Health condition(s) or Problem(s) studied | Chronic Kidney disease, Hyperkalemia |
Date of first enrollment | 04/01/2022 |
Target sample size | 1360 |
Countries of recruitment | Argentina,Japan,Bulgaria,Japan,China,Japan,Italy,Japan,Mexico,Japan,Russian Federation,Japan,Spain,Japan,Taiwan,Japan,Turkey,Japan,Ukraine,Japan,United States of America,Japan,Vietnam,Japan,Canada,Japan,India,Japan,Malaysia,Japan,Philippines,Japan,Poland,Japan,Thailand,Japan,Brazil,Japan |
Study type | Interventional |
Intervention(s) | - 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 - maintenance phase: randomized to SZC or placebo |
Outcome(s)
Primary Outcome | 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 ] |
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Secondary Outcome |
Key inclusion & exclusion criteria
Age minimum | >= 18age old |
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Age maximum | <= 130age old |
Gender | Both |
Include 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 for CKD, 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. |
Exclude 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 successfully treated basal cell or treated squamous cell carcinoma. - S-K 6.5 or more or 3.5 mmol/L less than 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 not approved for CKD 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. Note: For participants taking a fixed combination of an ACEi or ARB with another agent (eg, calcium blockers or diuretics) as SoC, the investigator must make a judgment that it will be safe and efficacious for such participants to change to the study ACEi or ARB and to the other drug as separate agents. - 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). |
Related Information
Primary Sponsor | Hibi Kazushige |
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Secondary Sponsor | |
Source(s) of Monetary Support | |
Secondary ID(s) | NCT05056727 |
Contact
Public contact | |
Name | Kazushige Hibi |
Address | 3-1, Ofuka-cho, Kita-ku, Osaka-shi Osaka Japan 530-0011 |
Telephone | +81-6-4802-3533 |
RD-clinical-information-Japan@astrazeneca.com | |
Affiliation | Astrazeneka K.K |
Scientific contact | |
Name | Kazushige Hibi |
Address | 3-1, Ofuka-cho, Kita-ku, Osaka-shi Osaka Japan 530-0011 |
Telephone | +81-6-4802-3533 |
RD-clinical-information-Japan@astrazeneca.com | |
Affiliation | Astrazeneka K.K |