A Multicentre, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety of Zibotentan/Dapagliflozin in Combination Compared to Zibotentan Monotherapy, Zibotentan/Dapagliflozin and Zibotentan Monotherapy Compared to Placebo in Participants With Cirrhosis
概览
- 阶段
- 2 期
- 干预措施
- Placebo (placebo matching zibotentan capsule and placebo matching dapagliflozin tablet)
- 疾病 / 适应症
- Liver Cirrhosis
- 发起方
- AstraZeneca
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Occurence of any of the following components of this composite endpoint: >2kg increase in body weight (office-based), >2 L increase in total body water, increase in 2 or more loop-diuretic equivalents, fluid retention adverse event (AE)
- 状态
- 已完成
- 最后更新
- 3个月前
概览
简要总结
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.
详细描述
The study is designed to evaluate the safety of zibotentan/dapagliflozin in combination as compared to zibotentan monotherapy as well as zibotentan/dapagliflozin in combination and zibotentan monotherapy as compared to placebo in patients with cirrhosis with or without a history of decompensation. The study will be conducted in approximately 52 study centers in North America, Asia and Europe.
研究者
入排标准
入选标准
- •≥ 18 and ≤ 80 years of age at the time of signing the informed consent.
- •Clinical and/or histological diagnosis of cirrhosis.
- •Note: Either history of decompensation or compensated cirrhosis with signs of CSPH, including varices at endoscopy or collaterals at imaging (within 12 months prior to screening), and/or liver stiffness using vibration controlled elastography, liver stiffness \> 25 kPa or \> 21 kPa, and platelets \< 150 × 10\^99 (at time of screening).
- •Model for end stage liver disease score (MELD) \<
- •Child-Pugh score \<
- •No ascites or ascites up to grade 2 without change in diuretic treatment within the last month prior to first dose of study intervention and no paracentesis within the last month.
- •No evidence of worsening of hepatic function (eg, no clinically significant change in signs, symptoms, or laboratory parameters of hepatic disease status) within the last month prior to dosing, as determined by the investigator or usual practitioner.
- •No current or prior (within 1 month of enrolment) medical treatment with an SGLT2 inhibitor or endothelin receptor antagonist.
- •On no or a stable dose of beta blockers, with no major dose changes within 1 month prior to the first dose of study intervention.
- •Males or females of non-childbearing potential:
排除标准
- •Any evidence of a clinically significant disease, which in the investigator's opinion makes it undesirable for the participant to participate in the study.
- •Alanine aminotransferase/transaminase or AST ≥ 150 U/L and/or total bilirubin
- •International normalised ratio \> 1.
- •Serum/plasma levels of albumin ≤ 28 g/L.
- •Platelet count \< 50 × 109L.
- •Acute kidney injury (AKI) within 3 months of screening.
- •History of encephalopathy of West Haven Grade 2 or higher
- •History of variceal haemorrhage within 6 months prior to screening.
- •Any history of hepatocellular carcinoma.
- •Any history of portal venous thrombosis.
研究组 & 干预措施
Treatment Group 1
Participants will receive once daily dose of placebo matching zibotentan capsule + placebo matching dapagliflozin tablet for 6 weeks
干预措施: Placebo (placebo matching zibotentan capsule and placebo matching dapagliflozin tablet)
Treatment Group 2
Participants will receive once daily zibotentan capsule + placebo matching dapagliflozin tablet for 6 weeks
干预措施: Zibotentan + placebo (placebo matching dapagliflozin tablet)
Treatment Group 3
Participants will receive once daily zibotentan capsule + dapagliflozin tablet 10 mg for 6 weeks
干预措施: Zibotentan + dapagliflozin
结局指标
主要结局
Occurence of any of the following components of this composite endpoint: >2kg increase in body weight (office-based), >2 L increase in total body water, increase in 2 or more loop-diuretic equivalents, fluid retention adverse event (AE)
时间窗: baseline to Week 6
To evaluate the effect of zibotentan/dapagliflozin and zibotentan monotherapy versus placebo on a composite endpoint of fluid retention
次要结局
- Change in body weight (kg) over time course of study(at Week 6)
- Absolute change in systolic and diastolic blood pressure(from baseline to Week 6)
- Change in total dosage of loop-diuretic equivalents use(from baseline to Week 6)
- Change from baseline in intracellular water volume(at Week 6)
- Occurence of either of the two components of this composite: 1. >3 L increase in total body water volume from baseline to Week 6 2. Increase in 3 or more loop-diuretics equivalents use(from baseline to Week 6)
- Change from baseline in body fat mass(at Week 6)
- Change from baseline in body weight(at Week 6)
- Change from baseline in total body water(at Week 6)
- Change from baseline in extracellular water volume(at Week 6)