A Phase III, Randomised, Multicentre, Double-blind Study to Evaluate the Efficacy, Safety, and Tolerability of Zibotentan/Dapagliflozin Compared to Dapagliflozin Alone in Participants With Chronic Kidney Disease and High Proteinuria

AstraZeneca296 sites in 2 countries1,835 target enrollmentNovember 7, 2023

ConditionsChronic Kidney Disease With High Proteinuria

InterventionsZibotentan/Dapagliflozin Dapagliflozin

DrugsZibotentan/Dapagliflozin Dapagliflozin

Overview

Phase: Phase 3
Intervention: Zibotentan/Dapagliflozin
Conditions: Chronic Kidney Disease With High Proteinuria
Sponsor: AstraZeneca
Enrollment: 1835
Locations: 296
Primary Endpoint: Change in eGFR from baseline
Status: Active, not recruiting
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase III, randomised, multicentre, double-blinded study to evaluate efficacy, safety and tolerability of treatment with zibotentan/dapagliflozin and dapagliflozin alone in participants with chronic kidney disease (CKD) and high proteinuria

Registry

clinicaltrials.gov

Start Date

November 7, 2023

End Date

January 22, 2027

Last Updated

2 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•Participants with NYHA class III or class IV Congestive HF at the time of enrolment.
•Participants hospitalised for HF during the last 6 month prior to screening.
•Evidence of rales or jugular venous distention on physical examination.
•Participants with type 1 diabetes mellitus.
•History of any life-threatening ventricular dysrhythmia (continuous or paroxysmal).
•Blood pressure above 160 mmHg systolic.
•Blood pressure below 90 mmHg systolic.
•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.
•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).

Arms & Interventions

Zibotentan/Dapagliflozin dose A or Zibotentan/Dapagliflozin dose B

Drug dose (dose A or B) are determined based on eGFR values. Participants will receive daily oral dose of zibotentan/dapagliflozin in fixed dose combination.

Intervention: Zibotentan/Dapagliflozin

Dapagliflozin alone

Participants will receive daily oral dose of dapagliflozin.

Intervention: Dapagliflozin

Outcomes

Primary Outcomes

Change in eGFR from baseline

Time Frame: At month 24

To determine whether zibotentan and dapagliflozin in fixed dose combination is superior to dapagliflozin alone to slow decline in kidney function

Secondary Outcomes

Change in Urine Albumin to Creatinine Ratio (UACR) from baseline to each participant's mean level(at Month 9)
Time to the first occurrence of any of the components of the renal composite endpoint of 40% sustained decline in eGFR or ESKD or renal death(Through study completion, approximately 38 months)
Change in Urine Protein to Creatinine Ratio (UPCR) from baseline to each participant's mean level(at Month 9)