NCT lookup

Inclusion Criteria:

* ≥ 18 years of age at the time of signing the informed consent.
* Diagnosis of CKD with eGFR ≥ 20 and \< 90 mL/min/1.73m2 AND UACR \> 700 mg/g (\> 79 mg/mmol) or UPCR \> 1000 mg/g (\> 113 mg/mmol).
* Body mass index (BMI) within the range ≤40 kg/m2.
* Female participants must be either - not of child-bearing potential or - women of childbearing potential (WOCBP) using at least one highly effective birth control method for at least 3 months prior to first dose of study intervention.
* All WOCBP must have a negative serum pregnancy test result at screening.
* Receiving RAASi therapy (ACEi or ARB), and for the patient maximum tolerated labelled daily dose, that has been stable for at least 4 weeks.

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.

• Aramil, Russia
• Izhevsk, Russia
• Krasnoyarsk, Russia
• Moscow, Russia
• Moscow, Russia
• Moscow, Russia
• Moscow, Russia
• Omsk, Russia
• Orenburg, Russia
• Perm, Russia
• Saint Petersburg, Russia
• Saratov, Russia
• Saratov, Russia
• Ulyanovsk, Russia
• Yaroslavl, Russia