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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 205
- 试验地点
- 51
- 主要终点
- Part B: Absolute change in HVPG from baseline to Week 6.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Part B: Absolute change in HVPG from baseline to Week 6.
时间窗: 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.
时间窗: at Week 6
To evaluate the change from baseline in HVPG on zibotentan and dapagliflozin in combination versus placebo.
次要结局
- Part A: Percent change in HVPG from baseline to Week 6.(at Week 6)
- 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)
- 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)
- Part A: Percentage and absolute change in total dosage of loop-diuretic equivalents use from baseline to Week 6.(at Week 6)
- 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)
- Part A: Change in systolic and diastolic blood pressure from baseline to Week 6.(at Week 6)
- 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)
- Part B: Change in systolic and diastolic blood pressure from baseline to Week 6 and Week 16.(at Week 6 and Week 16)
- Part B: Percentage change in HVPG from baseline to Week 6.(at Week 6)
- 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)
- 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)
- 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)