A Study to Investigate the Effects of Zibotentan/Dapagliflozin Combination Compared to Dapagliflozin Alone in Adult Participants with Chronic Kidney Disease and High Proteinuria - ZODIAC

Exclusion Criteria

• - Clinically significant, unstable, or uncontrolled medical condition which in the Investigator’s opinion makes it undesirable for the participant to participate in the study.
• - Known hypersensitivity to dapagliflozin or zibotentan or any of the excipients of the investigational product. History or ongoing allergy/hypersensitivity, as judged by the investigator, to SGLT2i therapy or ERAs.
• - NYHA class III or class IV HF.
• - Participants hospitalised for HF and/or who have not been stable on HF therapy during the last 6 months prior to screening.
• - HF due to cardiomyopathies that would primarily require other specific treatment.
• - High output HF (eg, due to hyperthyroidism or Paget’s disease).
• - HF due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement.
• - Evidence of rales or jugular venous distention on physical examination.
• - Type 1 diabetes mellitus.
• - History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal).
• - Participants hospitalised for heart disease or cardiac procedures or for COVID-19 during the last 3 months prior to screening.
• - History of solid organ transplantation or bone marrow transplant.
• - Any condition with a life expectancy of less than 1 year based on investigator´s clinical judgment.
• - Malignancy within the past 5 years. Exceptions to this criterion include non-melanoma skin cancer and curatively treated cervical carcinoma in situ.
• - Significant liver disease as judged by the investigator.
• - Renal replacement therapy or previous kidney transplant.
• - Known history of significant drug or alcohol abuse within 12 months of screening.
• - On treatment with strong or moderate CYP3A4 inducer.
• - On systemic immunosuppression therapy other than prespecified stable maintenance therapy.
• - Participants treated or expecting to be treated with tolvaptan (including as part of participation in a clinical trial), any other ERAs, or budesonide (where used to treat IBD or IgAN).
• - Systolic blood pressure above 160 mmHg and/or below 90 mmHg.
• - Significant impairment of liver function defined as AST or ALT >3 x upper limit of normal (ULN) or Total serum bilirubin >2 x ULN (an isolated increase in bilirubin in participants with known Gilbert’s syndrome is not a reason for exclusion).
• - NT-proBNP ≥ 600 pg/mL (or NT-proBNP ≥ 1200 pg/mL, if associated with atrial fibrillation) measured by local laboratory at screening.
• - Any of the following results of echocardiography at screening:
• • left ventricular ejection fraction (LVEF) < 50%
• • significant ventricular wall motion abnormality or severe cardiac valve abnormalities
• • isolated pulmonary arterial hypertension (as defined by local clinical practice) or right ventricular failure; in the absence of left-sided HF
• - Women who are pregnant, breast-feeding, or women with intent of getting pregnant.
• - Women who are not willing to use adequate contraception or cannot, in the opinion of the Investigator, understand and/or comply with the study requirements regarding contraception.