NCT04724837

Zibotentan and Dapagliflozin for the Treatment of CKD (ZENITH-CKD Trial)

A Phase 2b Multicentre, Randomised, Double-Blind, Active-Controlled, Parallel Group Dose-Ranging Study to Assess the Efficacy, Safety and Tolerability of Zibotentan and Dapagliflozin in Patients With Chronic Kidney Disease With Estimated Glomerular Filtration Rate (eGFR) ≥ 20 mL/Min/1.73 m^2

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 542 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

Summary

The purpose of the study is to assess efficacy, safety and tolerability of treatment with zibotentan and dapagliflozin in combination and dapagliflozin 10 mg as monotherapy in participants with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m\^2, and urinary albumin to creatinine ratio (UACR) ≥ 150 mg/g and ≤ 5000 mg/g.

Detailed description

The study will be conducted in approximately 220 sites in North America, South America, Africa, Asia/Pacific, and European countries. Participants will be randomized to 12 weeks of treatment plus 2 weeks follow-up. After screening, eligible participants will be stratified by diabetes (diabetic kidney disease \[DKD\] versus non-diabetes mellitus \[non-DM\] CKD) and baseline eGFR (below or equal versus above 45 mL/min/1.73m\^2). A total of 495 participants will be randomised into this study, including participants randomised under the earlier study design. Four hundred and fifteen (415) participants will be randomised to have 166 participants in zibotentan Dose A/dapagliflozin 10 mg combination arm and dapagliflozin 10 mg monotherapy arm, and 83 participants in the zibotentan Dose B/dapagliflozin 10 mg combination arm. * Zibotentan Dose A + Dapagliflozin 10 mg once daily. * Zibotentan Dose B + Dapagliflozin 10 mg once daily. * Placebo + Dapagliflozin 10 mg once daily Participants who were previously randomised cannot be re-randomised.

Conditions

• Chronic Kidney Disease

Interventions

Type	Name	Description
DRUG	Zibotentan	Participants will receive zibotentan as per the arms they are randomized.
DRUG	Dapagliflozin	Participants will receive 10 mg dapagliflozin as per the arms they are randomized.
DRUG	Placebo	Participants will receive placebo as per the arms they are randomized to.

Timeline

• Start date: 2021-04-28
• Primary completion: 2023-06-01
• Completion: 2023-06-01
• First posted: 2021-01-26
• Last updated: 2024-07-30
• Results posted: 2024-07-30

Locations

164 sites across 19 countries: United States, Argentina, Australia, Brazil, Bulgaria, Canada, Croatia, Denmark, Georgia, Hungary, Italy, Japan, Malaysia, Netherlands, Poland, Slovakia, South Africa, Spain, Ukraine

Regulatory

• FDA-regulated drug study