Part A Objectives Primary Objective: To evaluate the change from baseline in HVPG on zibotentan and dapagliflozin in combination versus placebo. Secondary Objectives: - 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. - To evaluate the effect of zibotentan and dapagliflozin in combination versus placebo on change in body weight. - To evaluate the effect of zibotentan and dapagliflozin in combination versus placebo on accumulated additional loop-diuretic equivalents use. - To evaluate the effect of zibotentan and dapagliflozin in combination versus placebo on body water volumes and body fat mass. - in combination versus placebo on changes in office-based systolic and diastolic blood pressure. Safety Objective: To assess the safety and tolerability of zibotentan and dapagliflozin in combination versus placebo. Part B Objectives Primary Objective: 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. Secondary Objectives: - To evaluate the change from baseline in HVPG on zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo. - To evaluate the effect of zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo on change in body weight. - To evaluate the effect of zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo on accumulated additional loop-diuretic equivalents use. - To evaluate the effect of zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo on body water volumes and body fat mass. - 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. Safety Objective: To assess the safety and tolerability of zibotentan and dapagliflozin in combination and dapagliflozin monotherapy versus placebo.
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