In short
Clinical trials are studying Zibotentan in people with liver cirrhosis and in people with chronic kidney disease and high proteinuria. These studies look at whether Zibotentan, alone or with dapagliflozin, can improve disease measures and safety outcomes. They include Phase 2 and Phase 3 research in different patient groups.
Key points
- Zibotentan is being studied in clinical trials for liver cirrhosis with portal hypertension and for chronic kidney disease with high proteinuria. The trial data include Phase 2, Phase 2b, and Phase 3 studies. In cirrhosis, researchers are mainly measuring HVPG and fluid retention-related outcomes over about 6 weeks. In kidney disease, the main focus is whether the treatment can slow the decline in kidney function by measuring eGFR over 24 months. Some trials test Zibotentan with dapagliflozin, while others compare the combination with placebo or with dapagliflozin alone.
Clinical trials overview
The trial data describe three interventional studies of Zibotentan, meaning the treatment is given to people and then compared with another group. Two studies are in liver disease, and one study is in kidney disease. The studies include Phase 2, Phase 2b, and Phase 3 research, so they range from earlier testing to a larger confirmatory trial.
Studies in liver cirrhosis
One completed Phase 2 study, called the ZEAL study, looked at people with liver cirrhosis and features of portal hypertension, which means high pressure in the blood vessels that go to the liver. This study compared Zibotentan and dapagliflozin in combination with placebo, and its main goal was to see the change in HVPG from baseline to Week 6. HVPG stands for hepatic venous pressure gradient, a test that helps show pressure in the liver blood flow system.
A second completed Phase 2b study, ZEAL-UNLOCK, looked at people with cirrhosis of the liver and focused on safety. The study examined Zibotentan and dapagliflozin, Zibotentan alone, and placebo groups, with attention to fluid retention, which means the body holding extra fluid and possibly causing weight gain or swelling. The main outcomes included body weight, total body water, body fat mass, blood pressure, and use of loop-diuretic equivalents over 6 weeks.
Study in chronic kidney disease
The Phase 3 study, NCT06087835, is authorised and is testing Zibotentan combined with dapagliflozin in people with chronic kidney disease and high proteinuria, which means too much protein in the urine. The study compares the fixed-dose combination with dapagliflozin alone and includes a large enrollment of 1833 people. Its main outcome is the change in eGFR from baseline to Month 24, which shows how well the kidneys are filtering blood.
What researchers measure
In the liver cirrhosis studies, researchers focus on pressure in the liver circulation and on signs of fluid buildup. These measures include HVPG, body weight, total body water, and changes in diuretic use, which are medicines that help the body remove extra fluid.
In the kidney study, the main measure is eGFR over 24 months, because this helps show whether kidney function declines more slowly. The study summary says the goal is to see whether the combination is superior to dapagliflozin alone in slowing kidney decline.
Who the trials include
The study populations are adults with liver cirrhosis, adults with liver cirrhosis and portal hypertension, or adults with chronic kidney disease and high proteinuria. The trial data do not give full eligibility rules, so exact entry criteria are not listed here.
Trial design and comparators
All three studies are interventional trials, so they compare one treatment approach with another approach or with placebo. In the liver studies, the trial data mention Zibotentan, dapagliflozin, placebo, and Zibotentan monotherapy in different groups. In the kidney study, the comparison is between the Zibotentan plus dapagliflozin combination and dapagliflozin alone.