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)

Korábbi kezelés

• Participants hospitalised for HF during the last 6 month prior to screening.
• Participants hospitalised for heart disease or cardiac procedures or for COVID-19 during the last 3 months prior to screening.
• Participants on renal replacement therapy or previous kidney transplant.
• Participants on treatment with strong or moderate CYP3A4 inducer.
• 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.
• Participants treated or expecting to be treated with tolvaptan, any other ERAs, or budesonide (where used to treat IBD or IgAN).
• Previous randomisation in the present study.

Más betegség

• Participants with type 1 diabetes mellitus.
• History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal).
• History of solid organ transplantation or bone marrow transplant.
• 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).
• Any condition with a life expectancy of less than 2 years 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.
• Known blood-borne diseases.
• Clinically significant, unstable, or uncontrolled medical condition as assessed by the Investigator.
• Known history of drug or alcohol abuse within 12 months of screening.
• Inability of the participant, in the opinion of the investigator, to understand and/or comply with IMP, procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the participant unable to complete the study.

Laborértékek

• 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.

Egyéb

• Participants with NYHA class III or class IV Congestive HF at the time of enrolment.
• Evidence of rales or jugular venous distention on physical examination.
• Blood pressure above 160 mmHg systolic.
• Blood pressure below 90 mmHg systolic.
• Participation in another clinical study with a study intervention administered in the last 3 months.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• 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 procedures.

• Participant must be ≥ 18 years of age and of legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.
• Diagnosis of CKD, defined as eGFR ≥ 20 and < 90 mL/min/1.73 m2 and UACR > 700 mg/g (> 79 mg/mmol) or UPCR > 1000 mg/g (> 113 mg/mmoL).
• All female participants must have a negative serum pregnancy test result at screening.
• Female participants must be either
  • not of child-bearing potential or
  • women of child bearing potential (WOCBP) using at least one highly effective birth control method for at least 3 months prior to first dose of study intervention
• Capable of giving signed informed consent
• Provision of signed informed consent prior to any study specific procedure.
• Provision of electronic informed consent prior to completion of the optional Study Participant Feedback Questionnaire (SPFQ).
• Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics imitative research that supports the Genomic Initiative.
• Receiving RAASi therapy (ACEi or ARB), and for the patient maximum tolerated labelled daily dose, that has been stable for at least 4 weeks.