A Study to Evaluate the Safety, Tolerability, PK, and PD Effects of AZD2389 in Participants With Liver Fibrosis and Compensated Cirrhosis.

AstraZeneca40 enrolled

Overview

The purpose of this study is to measure the safety, tolerability, and the way the body absorbs, distributes, and metabolises AZD2389 as compared to placebo in participants with liver fibrosis and compensated cirrhosis. The study will also examine how the drug acts on the body

Study details include: The study duration will be up to 63 days (9 weeks). * 1 or 2 screening visits (up to 28 days before treatment) * 28 days of treatment including 5 clinic visits * Week 1: 24-hour in-clinic stay (Day 1) * Week 2: Outpatient clinic visit (Day 7) * Week 3: Outpatient clinic visit (Day 14) * Week 4: Telephone visit (Day 21) * Week 5: 24 to 48-hour in-clinic stay (Day 28) * Week 6: Follow-up visit (Day 35) Disclosure Statement: The study consists of two cohorts, each with a parallel-group design and two arms, with participants blinded to treatment allocation. Number of Participants: The study will randomise approximately 36 participants in total. Cohort A: Approximately 75 participants with presumed MASH/NASH with fibrosis will be screened such that approximately 18 participants will be randomised. Twelve participants will be randomised to receive AZD2389 and 6 participants will receive placebo. Cohort B: Approximately 75 participants with SLD with advanced fibrosis including compensated cirrhosis will be screened such that approximately 18 participants will be randomised. Twelve participants will be randomised to receive AZD2389 and 6 participants will receive placebo

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Liver Fibrosis Hepatic Cirrhosis

Interventions

AZD2389DRUG

Doses of AZD2389 or placebo will be administered orally.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key inclusions: * Males/females aged ≥ 18 years * Indications: Presumed MASH (cohort A) or other steatotic liver disease (cohort B) with fibrosis * No significant change in weight over the last 6 months * Barrier contraceptives use by males * Capable of informed consent * Judged to be suitable for study by investigator Key exclusions: * A condition that could put the participant at risk, influence the participant's ability to participate in the trial, interfere with evaluation of the study intervention or affect the interpretation of the results * Other causes of liver disease which are not the principal inclusion criteria for each cohort * Significant elevations in liver blood tests or platelets \<140 x10\^9/L * Decompensated liver disease, hepatobiliary cancer or listing for liver transplantation * Bleeding disorders or major bleeding risk * HIV infection or hepatitis B infection * Clinically significant cardiovascular (e.g. severe ischaemic heart disease, severe heart failure or cardiac dysrhythmia) or cerebrovascular disease within the past 3 months * Stage 2 hypertension * eGFR \<60ml/min/1.73m2 * Clinically significant gastrointestinal disease which can affect the interpretation of pharmacokinetic, safety, and tolerability data * Skin disorders or ongoing wound healing * Psychiatric disorders which may negatively affect participation in the trial. * Females of childbearing potential

Locations (9)

Research Site

Chandler, Arizona, United States

Research Site

Rialto, California, United States

Research Site

Atlanta, Georgia, United States

Research Site

Morehead City, North Carolina, United States

Outcomes

Primary Outcomes

Notable Trends in Laboratory Assessments (Haematology, Coagulation, Clinical Chemistry, Fibrinolysis, and Urinalysis)

The number of participants with notable trends in laboratory assessments (haematology, coagulation, clinical chemistry, fibrinolysis, and urinalysis) is presented. Notable trends were assessed based on evaluation of mean values over time, individual participant values, and clinically important abnormalities, including values outside predefined criteria.

Time frame: From screening up to and including Day 35

Clinically Relevant Trends in Vital Signs (Blood Pressure, Pulse Rate, Oxygen Saturation, Body Temperature, and Respiration Rate), and 12-lead Electrocardiogram (ECG)

The number of participants with clinically relevant trends in vital signs (blood pressure, pulse rate, oxygen saturation, body temperature, and respiration rate), and12-lead ECGs is presented. Clinically relevant trends were assessed based on trends or group changes over time, changes in individual participants over time, and individual clinically important abnormalities.

Time frame: From Screening up to and including Day 35

Secondary Outcomes

Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Cmax

The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Cmax= Maximum Concentration

Time frame: Day 1 and Day 28

Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Tmax

The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. tmax = Time to Maximum Concentration

Time frame: Day 1 and Day 28

Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: t1/2 Lambda z

The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. t1/2 lambda z= Apparent Terminal Half-life

Data from ClinicalTrials.gov

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