Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Study Principal Inclusion Criteria For Both Part A and Part B:
1. No current or prior (within 1 month of enrolment) medical treatment with an SGLT2
inhibitor or endothelin receptor antagonist.
2. 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.
3. Provision of signed and dated, written ICF prior to any mandatory study-specific
procedures, sampling, and analyses.
4. Female participants of non-childbearing potential confirmed at screening by fulfilling
one of the following criteria:
1. Post-menopausal: defined as amenorrhoea for at least 12 months or more following
cessation of all exogenous hormonal treatments; and FSH levels in the
post-menopausal range.
2. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral
oophorectomy or bilateral salpingectomy but not tubal ligation.
5. Female participants must have a negative pregnancy test at screening and randomisation
and must not be lactating
Part A participants who have the following:
1. Clinical and/or histological diagnosis of cirrhosis with either (i) features of portal
hypertension or (ii) liver stiffness ≥ 21 kPa.
2. MELD score < 15.
3. Child-Pugh score ≤ 6.
4. No clinically evident ascites
5. 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.
6. HVPG recording of good enough quality as judged by a central reader.
Part B participants who have the following:
1. Clinical and/or histological diagnosis of cirrhosis with features of portal
hypertension.
2. MELD score < 15.
3. Child-Pugh score < 10.
4. 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.
5. 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.
6. HVPG recording of good enough quality as judged by a central reader.
Study Principal Exclusion Criteria:
1. Any evidence of a clinically significant disease which in the investigator's opinion
makes it undesirable for the participant to participate in the study.
2. Liver cirrhosis caused by chronic cholestatic liver disease
3. ALT or AST ≥ 150 U/L and/or total bilirubin ≥ 3 × ULN
4. Acute liver injury caused by drug toxicity or by an infection.
5. Any history of hepatocellular carcinoma.
6. Liver transplant or expected liver transplantation within 6 months of screening.
7. History of TIPS or a planned TIPS within 6 months from enrolment into the study.
8. Active treatment for HCV within the last 1 year or HBV antiviral therapy for less than
1 year.
9. Participants with T1DM.
Medical Conditions (Part A only)
1. INR > 1.5.
2. Serum/plasma levels of albumin ≤ 35 g/L.
3. Platelet count < 75 × 109/L.
4. History of ascites
5. History of hepatic hydrothorax
6. History of portopulmonary syndrome
7. History of hepatic encephalopathy
8. History of variceal haemorrhage
9. History of acute kidney injury
10. History of heart failure, including high output heart failure (eg, due to
hyperthyroidism or Paget's disease)
Medical Conditions (Part B only)
1. INR > 1.7.
2. Serum/plasma levels of albumin ≤ 28 g/L.
3. Platelet count < 50 × /109L.
4. Acute kidney injury within 3 months of screening.
5. History of encephalopathy of West Haven grade 2 or higher.
6. History of variceal haemorrhage within 6 months prior to screening.
7. 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.
8. 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).
9. High output heart failure (eg, due to hyperthyroidism or Paget's disease).
10. Heart failure due to primary cardiac valvular disease/dysfunction, severe functional
mitral or tricuspid valve insufficiency, or planned cardiac valve repair/replacement.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 11/3/22. Questions regarding updates should be directed to the study team contact.