Study to Investigate Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin in Participants with Chronic Kidney Disease and High Proteinuria (ZENITH High Proteinuria)

Exclusion Criteria

• 1.Participants with NYHA class III or class IV Congestive HF at the time of enrolment.
• 2. Participants hospitalised for HF during the last 6 month prior to screening.
• 3. Evidence of rales or jugular venous distention on physical examination.
• 4. Participants with type 1 diabetes mellitus.
• 5. History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal).
• 6. Blood pressure above 160 mmHg systolic.
• 7. Blood pressure below 90 mmHg systolic.
• 8. Participants hospitalised for heart disease or cardiac procedures or for COVID-19 during the last 3 months prior to screening.
• 9. History of solid organ transplantation or bone marrow transplant.
• 10. History or ongoing allergy/hypersensitivity, as judged by the Investigator, to SGLT2i therapy (eg, dapagliflozin, canagliflozin, empagliflozin or other SGLT2 inhibitors) or Endothelin Receptor Antagonists (eg, ambrisentan, atrasentan, bosentan, or other).
• 11. Any condition with a life expectancy of less than 2 years based on investigator´s clinical judgment.
• 12. Malignancy within the past 5 years. Exceptions to this criterion include non-melanoma skin cancer and curatively treated cervical carcinoma in situ.
• 13. Significant liver disease as judged by the investigator or severe
• hepatic impairment with AST or ALT > 3 × ULN; or total bilirubin > 2 × ULN at time of screening. An isolated increase in bilirubin in participants with known Gilbert's syndrome is not a reason for exclusion.
• 14. Known blood-borne diseases.
• 15. Clinically significant, unstable, or uncontrolled medical condition as assessed by the Investigator.
• 16. Participants on renal replacement therapy or previous kidney transplant.
• 17. Known history of drug or alcohol abuse within 12 months of screening.
• 18. Participants on treatment with strong or moderate CYP3A4 inducer.
• 19.Participants on systemic immunosuppression therapy other than stable maintenance therapy defined as prednisone 10 mg/day (or equivalent) or less, aziothioprine 100 mg/day or less; MMF 1000 mg/day or less for at least 3 months prior to Visit 1. Inhaled, nasal or dermatological steroids are also allowed.
• 20.Participants treated or expecting to be treated with tolvaptan, any other ERAs, or budesonide (where used to treat IBD or IgAN).
• 21. Participation in another clinical study with a study intervention administered in the last 3 months.