ZEAL
Research type
Research Study
Full title
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
IRAS ID
1010024
Contact name
Assia Bensalem
Contact email
Sponsor organisation
AstraZeneca AB
Eudract number
2021-006577-30
Clinicaltrials.gov Identifier
Research summary
Liver cirrhosis is severe scarring of the liver and a serious consequence of many liver diseases. People with liver cirrhosis experience life-threatening complications mostly caused by high blood pressure within the liver, called portal hypertension. Reducing the portal
hypertension has been shown to reduce the risk for the most severe complications of cirrhosis and death. There is a major clinical need for additional and better treatments to reduce portal hypertension in people living with cirrhosis.
In this study, it is investigated if treatment with zibotentan and dapagliflozin, or dapagliflozin only are safe and could help treat portal hypertension in people with cirrhosis as compared to placebo. Zibotentan is an investigational drug not yet approved, while dapagliflozin is
approved for treatment of type 2 diabetes, heart failure and chronic kidney disease. Zibotentan taken on its own may decrease portal hypertension but could cause fluid buildup in the body when taken alone. Dapagliflozin may help lower the risk of fluid buildup caused by
zibotentan, and may also on its own help treat medical problems associated with cirrhosis.
The trial is broken into 2 parts. Part A was a small study on participants with liver cirrhosis without any complications. It is completed and results showed that the combination of zibotentan and dapagliflozin was safe and tolerable.
Part B includes participants with cirrhosis with and without complications. The study consists of a screening, treatment, and a follow-up visit, in total 11 visits. Participants will be divided into 5 different groups: zibotentan at 3 different doses in combination with dapagliflozin and
dapagliflozin alone compared with the results from placebo group. The main objectives is to investigate the effect on portal hypertension, safety and tolerability of the treatments.
Participation is voluntary and before any study procedures informed consent will be required.REC name
South Central - Berkshire B Research Ethics Committee
REC reference
24/SC/0185
Date of REC Opinion
12 Jul 2024
REC opinion
Further Information Favourable Opinion