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

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.

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

What this study is about

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

What this study is about