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

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

Brief Summary:
The purpose of the study is to assess efficacy, safety and tolerability of treatment with zibotentan and dapagliflozin in combination and alone, compared with placebo in participants with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) between 20 and 60 mL/min/1.73m².

Detailed Description:
The study will be conducted in approximately 200 sites in North America, South America, Africa, Asia/Pacific, and European countries.

The study will be conducted in 2 parts, Part A and Part B. In both study parts, 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 versus above 45 mL/min/1.73m²).

Participants will be randomized to treatments with 4 arms in Part A and 6 arms in Part B, in addition to receiving background local standard of care (SoC) therapy as follows:

Part A:
- Zibotentan Dose A + Dapagliflozin 10 mg once daily.
- Zibotentan Dose A once daily.
- Dapagliflozin 10 mg once daily.
- Placebo once daily.

Part B:
- Zibotentan Dose A + Dapagliflozin 10 mg once daily.
- Zibotentan Dose A once daily.
- Dapagliflozin 10 mg once daily.
- Placebo once daily.
- Zibotentan Dose B + Dapagliflozin 10 mg once daily.
- Zibotentan Dose C+ Dapagliflozin 10 mg once daily.

Participants randomized in Part A cannot be randomized in Part B.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 660 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2b Multicentre, Randomised, Double-Blind, Placebo-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) Between 20 and 60 mL/Min/1.73 m²
Actual Study Start Date: April 28, 2021
Estimated Primary Completion Date: July 4, 2022
Estimated Study Completion Date: July 4, 2022

Arm:
- Experimental: Part A and Part B: Zibotentan Dose A + Dapagliflozin
- Experimental: Part A and Part B: Zibotentan Dose A
- Experimental: Part A and Part B: Dapagliflozin
- Placebo Comparator: Part A and Part B: Placebo
- Experimental: Part B Only: Zibotentan Dose B + Dapagliflozin
- Experimental: Part B Only: Zibotentan Dose C + Dapagliflozin

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