Zibotentan and Dapagliflozin Combination, EvAluated in Liver Cirrhosis (ZEAL Study)
- Conditions
- Liver Cirrhosis
- Registration Number
- NCT05516498
- Lead Sponsor
- AstraZeneca
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 195
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Part B: Absolute change in HVPG from baseline to Week 6. at Week 6 To evaluate the change from baseline in HVPG on zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo.
Part A: Absolute change in HVPG from baseline to Week 6. at Week 6 To evaluate the change from baseline in HVPG on zibotentan and dapagliflozin in combination versus placebo.
- Secondary Outcome Measures
Name Time Method Part A: Percent change in HVPG from baseline to Week 6. at Week 6 To evaluate the change from baseline in HVPG on zibotentan and dapagliflozin in combination versus placebo.
Part B: Absolute change in total dosage of loop-diuretic equivalents use from baseline to Week 6 and Week 16. at Week 6 and Week 16 To evaluate the effect of zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo on total loop-diuretic equivalents use.
Part A: Evaluation of change in body weight (kg) over time course of study. Percentage and absolute change from baseline in body weight at Week 6. at Week 6 To evaluate the effect of zibotentan and dapagliflozin in combination versus placebo on change in body weight.
Part A: Percentage and absolute change in total dosage of loop-diuretic equivalents use from baseline to Week 6. at Week 6 To evaluate the effect of zibotentan and dapagliflozin in combination versus placebo on total loop-diuretic equivalents use.
Part A: Change in total body water, extracellular water and intracellular water volumes from baseline to Week 6. Change in total body fat mass from baseline to Week 6. at Week 6 To evaluate the effect of zibotentan and dapagliflozin in combination versus placebo on body water volumes and body fat mass.
Part A: Change in systolic and diastolic blood pressure from baseline to Week 6. at Week 6 To evaluate the effect of zibotentan and dapagliflozin in combination versus placebo on changes in office-based systolic and diastolic blood pressure.
Part A: HVPG response, where a responder is defined as HVPG < 10 mmHg or a reduction in HVPG of ≥ 1.5 mmHg from baseline to Week 6. at Week 6 To evaluate the proportion of participants achieving HVPG \< 10 mmHg or a reduction in HVPG of ≥ 1.5 mmHg on zibotentan and dapagliflozin versus placebo.
Part B: Change in systolic and diastolic blood pressure from baseline to Week 6 and Week 16. at Week 6 and Week 16 To evaluate the effect of zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo on changes in office-based systolic and diastolic blood pressure.
Part B: Percentage change in HVPG from baseline to Week 6. at Week 6 To evaluate the change from baseline in HVPG on zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo.
Part B: Evaluation of change in body weight (kg) over time course of study. Percentage and absolute change from baseline in body weight at Week 6 and Week 16. at Week 6 and Week 16 To evaluate the effect of zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo on change in body weight.
Part B: HVPG response, where a responder is defined as at least 20% decrease or a reduction to or below 12 mmHg in HVPG from baseline to Week 6. at Week 6 To evaluate the proportion of participants achieving at least 20% decrease in HVPG or a reduction to or below 12 mmHg in HVPG on zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo.
Part B: Change in total body water, extracellular water and intracellular water volumes from baseline to Week 6 and Week 16. Change in total body fat mass from baseline to Week 6 and Week 16. at Week 6 and Week 16 To evaluate the effect of zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo on body water volumes and body fat mass.
Trial Locations
- Locations (1)
Research Site
🇬🇧Nottingham, United Kingdom