Zibotentan and Dapagliflozin combination, EvAluated in Liver cirrhosis (ZEAL study)

Phase 1

• Conditions: iver cirrhosis with features of portal hypertension.; MedDRA version: 20.0Level: LLTClassification code 10024667Term: Liver cirrhosisSystem Organ Class: 100000004871; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2021-006577-30-BE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-09-30
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

Study principal inclusion criteria:
Participant must be aged 18 years and = 80 years of age at the time of signing the
informed consent.

Part A participants who have the following:
(a) Clinical and/or histological diagnosis of cirrhosis with either (i) features of portal
hypertension or (ii) liver stiffness = 21 kPa.
(b) MELD score < 15.
(c) Child-Pugh score = 6.
(d) No clinically evident ascites
(e) 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.
(f) HVPG recording of good enough quality as judged by a central reader.

Part B participants who have the following:
(a) Clinical and/or histological diagnosis of cirrhosis with features of portal
hypertension.
(b) MELD score < 15.
(c) Child-Pugh score < 10.
(d) No ascites or ascites up to grade 2 without change in diuretic treatment within the last
month prior to first dose and no paracentesis within the last month or planned
paracentesis in the next 4 months at screening.
(e) 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.
(f) HVPG recording of good enough quality as judged by a central reader.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

Study principal exclusion criteria:
a)Any evidence of a clinically significant disease which in the investigator’s opinion makes it undesirable for the participant to participate in the study.
b)Liver cirrhosis caused by chronic cholestatic liver disease
c)ALT or AST = 150 U/L and/or total bilirubin = 3 × ULN
d)Acute liver injury caused by drug toxicity or by an infection.
e)Any history of hepatocellular carcinoma.
f)Liver transplant or expected liver transplantation within 6 months of screening.
g)History of TIPS or a planned TIPS within 6 months from enrolment into the study.
h)Active treatment for HCV within the last 1 year or HBV antiviral therapy for less than 1 year.
i)Participants with T1DM.

Medical Conditions (Part A only)
a)INR > 1.5.
b)Serum/plasma levels of albumin = 35 g/L.
c)Platelet count < 75 × 109/L.
d)History of ascites
e)History of hepatic hydrothorax
f)History of portopulmonary syndrome
g)History of hepatic encephalopathy
h)History of variceal haemorrhage
i)History of acute kidney injury
j)History of heart failure, including high output heart failure (eg, due to hyperthyroidism or Paget’s disease)

Medical Conditions (Part B only)
a)INR > 1.7.
b)Serum/plasma levels of albumin = 28 g/L.
c)Platelet count < 50 × /109L.
d)Acute kidney injury within 3 months of screening.
e)History of encephalopathy of West Haven grade 2 or higher.
f)History of variceal haemorrhage within 6 months prior to screening.
g)NYHA functional heart failure class III or IV or with unstable heart failure requiring hospitalisation for optimisation of heart failure treatment and who are not yet stable on heart failure therapy within 6 months prior to screening.
h)Heart failure due to cardiomyopathies that would primarily require specific other treatment: eg, cardiomyopathy due to pericardial disease, amyloidosis or other infiltrative diseases, cardiomyopathy related to congenital heart disease, primary hypertrophic cardiomyopathy, cardiomyopathy related to toxic or infective conditions (ie, chemotherapy, infective myocarditis, septic cardiomyopathy).
i)High output heart failure (eg, due to hyperthyroidism or Paget’s disease).
j)Heart failure due to primary cardiac valvular disease/dysfunction, severe functional mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified