NCT05516498

Zibotentan and Dapagliflozin Combination, EvAluated in Liver Cirrhosis (ZEAL Study)

A Two Part Phase IIa/b Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Dose-ranging Study to Assess Efficacy, Safety, and Tolerability of the Combination of Zibotentan and Dapagliflozin, and Dapagliflozin Monotherapy Versus Placebo in Participants With Cirrhosis With Features of Portal Hypertension

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 205 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a two part Phase IIa/b multicentre, randomised, double-blind, placebo-controlled, parallel group dose-ranging study to assess the efficacy, safety, and tolerability of the combination of zibotentan and dapagliflozin, and dapagliflozin monotherapy versus placebo in participants with cirrhosis with features of portal hypertension.

Detailed description

Part A will assess the efficacy, safety, and tolerability of the combination of B mg zibotentan and 10 mg dapagliflozin versus placebo in participants with Child-Pugh A cirrhosis with features of portal hypertension and with no history of decompensation events. If the safety profile is determined to be acceptable at the conclusion of Part A, Part B will investigate efficacy, safety, and tolerability of A mg, B mg, or C mg zibotentan combined with 10 mg dapagliflozin and of 10 mg dapagliflozin monotherapy versus placebo in participants with cirrhosis with features of portal hypertension. Part B will include a broader range of Child- Pugh A and Child-Pugh B cirrhosis participants, including those with more severe disease, a history of decompensation events, or current ascites. The study will be conducted in approximately 30 to 45 study centres in North America, Asia, and Europe.

Conditions

• Liver Cirrhosis

Interventions

Type	Name	Description
DRUG	Part A: Placebo (matching zibotentan capsule & matching dapagliflozin tablet)	placebo capsule (matching zibotentan capsule) placebo tablet (matching dapagliflozin tablet)
DRUG	Part A: zibotentan (dose B) + dapagliflozin	zibotentan capsule dapagliflozin tablet
DRUG	Part B: Placebo (matching zibotentan capsule & matching dapagliflozin tablet)	placebo capsule (matching zibotentan capsule) placebo tablet (matching dapagliflozin tablet)
DRUG	Part B: placebo (matching zibotentan capsule) + dapagliflozin	placebo capsule (matching zibotentan capsule) dapagliflozin tablet
DRUG	Part B: zibotentan (dose A) + dapagliflozin	zibotentan capsule dapagliflozin tablet
DRUG	Part B: zibotentan (dose B) + dapagliflozin	zibotentan capsule dapagliflozin tablet
DRUG	Part B: zibotentan (dose C) + dapagliflozin	zibotentan capsule dapagliflozin tablet

Timeline

• Start date: 2022-10-31
• Primary completion: 2025-05-22
• Completion: 2025-07-17
• First posted: 2022-08-25
• Last updated: 2025-08-15

Locations

50 sites across 15 countries: United States, Australia, Austria, Belgium, China, Czechia, Denmark, France, Germany, Netherlands, Romania, Spain, Switzerland, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study