Zibotentan + Dapagliflozin for Liver Cirrhosis

(ZEAL UNLOCK Trial)

Recruiting at 40 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: AstraZeneca

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a Phase IIb multicentre, randomised, double-blind, parallel-group, placebo-controlled study to evaluate the safety of zibotentan/dapagliflozin in combination as compared to zibotentan monotherapy as well as zibotentan/dapagliflozin and zibotentan monotherapy as compared to placebo in patients with cirrhosis.

Eligibility Criteria

This trial is for adults aged 18-80 with a clinical or histological diagnosis of cirrhosis, but stable liver function and no recent treatments that could affect the study. They must not have severe liver disease (MELD < 15, Child-Pugh < 10), significant ascites, or changes in certain medications recently. Men must agree to contraception use.

Inclusion Criteria

I am between 18 and 80 years old.

Model for end stage liver disease score (MELD) < 15

I am not taking beta blockers or my dose has been stable.

Exclusion Criteria

I am not allergic to specific drugs required for the trial.

Clinically significant diseases affecting participation

I recently had a sudden decrease in kidney function.

Treatment Details

Interventions

• Dapagliflozin (SGLT2 Inhibitor)
• Zibotentan (Endothelin Receptor Antagonist)
• Zibotentan/Dapagliflozin (Combination Therapy)

Trial Overview The ZEAL-UNLOCK trial is testing the safety of combining zibotentan with dapagliflozin versus zibotentan alone and against a placebo in patients with cirrhosis. Participants are randomly assigned to one of these groups without knowing which they're receiving.

Participant Groups

Group I: Treatment Group 3 Experimental Treatment 1 Intervention

Participants will receive once daily zibotentan capsule + dapagliflozin tablet 10 mg for 6 weeks

Group II: Treatment Group 2 Experimental Treatment 1 Intervention

Participants will receive once daily zibotentan capsule + placebo matching dapagliflozin tablet for 6 weeks

Group III: Treatment Group 1 Placebo Group 1 Intervention

Participants will receive once daily dose of placebo matching zibotentan capsule + placebo matching dapagliflozin tablet for 6 weeks

Dapagliflozin is already approved in Canada for the following indications:

Approved in Canada as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology