Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, PK, and PD Effects of AZD2389 in Participants With Liver Fibrosis and Compensated Cirrhosis. (NCT NCT06750276)
NCT ID: NCT06750276
Last Updated: 2026-07-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
40 participants
Primary outcome timeframe
From screening up to and including Day 35
Results posted on
2026-07-06
Participant Flow
A total of 95 participants were screened for the study at 9 centres (1 in the UK and 8 in the US).
Of the 95 participants, 40 were eligible for the study: 22 with presumed MASH/NASH with fibrosis (Cohort A) and 18 with underlying SLDs of varying aetiologies (Cohort B).
Participant milestones
| Measure |
Cohort A - AZD2389
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
14
|
8
|
12
|
6
|
|
Overall Study
COMPLETED
|
14
|
8
|
12
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Full Analysis Set
Baseline characteristics by cohort
| Measure |
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
n=8 Participants
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
Cohort B - Placebo
n=6 Participants
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
58.9 years
STANDARD_DEVIATION 12.8 • n=9 Participants
|
57.5 years
STANDARD_DEVIATION 10.2 • n=27 Participants
|
54.8 years
STANDARD_DEVIATION 7.1 • n=267 Participants
|
55.5 years
STANDARD_DEVIATION 10.2 • n=265 Participants
|
56.9 years
STANDARD_DEVIATION 10.2 • n=568 Participants
|
|
Age, Customized
18 - < 65
|
8 Participants
n=9 Participants • Full Analysis Set
|
6 Participants
n=27 Participants • Full Analysis Set
|
12 Participants
n=267 Participants • Full Analysis Set
|
4 Participants
n=265 Participants • Full Analysis Set
|
30 Participants
n=568 Participants • Full Analysis Set
|
|
Age, Customized
>= 65
|
6 Participants
n=9 Participants • Full Analysis Set
|
2 Participants
n=27 Participants • Full Analysis Set
|
0 Participants
n=267 Participants • Full Analysis Set
|
2 Participants
n=265 Participants • Full Analysis Set
|
10 Participants
n=568 Participants • Full Analysis Set
|
|
Sex: Female, Male
Female
|
7 Participants
n=9 Participants • Full Analysis Set
|
4 Participants
n=27 Participants • Full Analysis Set
|
2 Participants
n=267 Participants • Full Analysis Set
|
4 Participants
n=265 Participants • Full Analysis Set
|
17 Participants
n=568 Participants • Full Analysis Set
|
|
Sex: Female, Male
Male
|
7 Participants
n=9 Participants • Full Analysis Set
|
4 Participants
n=27 Participants • Full Analysis Set
|
10 Participants
n=267 Participants • Full Analysis Set
|
2 Participants
n=265 Participants • Full Analysis Set
|
23 Participants
n=568 Participants • Full Analysis Set
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
9 Participants
n=9 Participants • Full Analysis Set
|
8 Participants
n=27 Participants • Full Analysis Set
|
11 Participants
n=267 Participants • Full Analysis Set
|
6 Participants
n=265 Participants • Full Analysis Set
|
34 Participants
n=568 Participants • Full Analysis Set
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
5 Participants
n=9 Participants • Full Analysis Set
|
0 Participants
n=27 Participants • Full Analysis Set
|
1 Participants
n=267 Participants • Full Analysis Set
|
0 Participants
n=265 Participants • Full Analysis Set
|
6 Participants
n=568 Participants • Full Analysis Set
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=9 Participants • Full Analysis Set
|
0 Participants
n=27 Participants • Full Analysis Set
|
1 Participants
n=267 Participants • Full Analysis Set
|
0 Participants
n=265 Participants • Full Analysis Set
|
1 Participants
n=568 Participants • Full Analysis Set
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=9 Participants • Full Analysis Set
|
0 Participants
n=27 Participants • Full Analysis Set
|
0 Participants
n=267 Participants • Full Analysis Set
|
0 Participants
n=265 Participants • Full Analysis Set
|
0 Participants
n=568 Participants • Full Analysis Set
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=9 Participants • Full Analysis Set
|
0 Participants
n=27 Participants • Full Analysis Set
|
1 Participants
n=267 Participants • Full Analysis Set
|
0 Participants
n=265 Participants • Full Analysis Set
|
2 Participants
n=568 Participants • Full Analysis Set
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
0 Participants
n=9 Participants • Full Analysis Set
|
0 Participants
n=27 Participants • Full Analysis Set
|
0 Participants
n=267 Participants • Full Analysis Set
|
0 Participants
n=265 Participants • Full Analysis Set
|
0 Participants
n=568 Participants • Full Analysis Set
|
|
Race/Ethnicity, Customized
Not reported
|
0 Participants
n=9 Participants • Full Analysis Set
|
0 Participants
n=27 Participants • Full Analysis Set
|
0 Participants
n=267 Participants • Full Analysis Set
|
0 Participants
n=265 Participants • Full Analysis Set
|
0 Participants
n=568 Participants • Full Analysis Set
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=9 Participants • Full Analysis Set
|
0 Participants
n=27 Participants • Full Analysis Set
|
0 Participants
n=267 Participants • Full Analysis Set
|
0 Participants
n=265 Participants • Full Analysis Set
|
0 Participants
n=568 Participants • Full Analysis Set
|
|
Race/Ethnicity, Customized
White
|
13 Participants
n=9 Participants • Full Analysis Set
|
8 Participants
n=27 Participants • Full Analysis Set
|
10 Participants
n=267 Participants • Full Analysis Set
|
6 Participants
n=265 Participants • Full Analysis Set
|
37 Participants
n=568 Participants • Full Analysis Set
|
|
Region of Enrollment
USA
|
14 Participants
n=9 Participants • Full Analysis Set
|
8 Participants
n=27 Participants • Full Analysis Set
|
12 Participants
n=267 Participants • Full Analysis Set
|
6 Participants
n=265 Participants • Full Analysis Set
|
40 Participants
n=568 Participants • Full Analysis Set
|
PRIMARY outcome
Timeframe: From screening up to and including Day 35Population: Safety analysis set. All participants who were randomised and received at least one dose of study intervention were analysed.
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.
Outcome measures
| Measure |
Cohort B - Placebo
n=6 Participants
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
n=8 Participants
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Notable Trends in Laboratory Assessments (Haematology, Coagulation, Clinical Chemistry, Fibrinolysis, and Urinalysis)
|
0 Participants
0
|
0 Participants
0
|
0 Participants
0
|
0 Participants
0
|
PRIMARY outcome
Timeframe: From Screening up to and including Day 35Population: Safety analysis set. All participants who were randomised and received at least one dose of study intervention were analysed.
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.
Outcome measures
| Measure |
Cohort B - Placebo
n=6 Participants
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
n=8 Participants
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Clinically Relevant Trends in Vital Signs (Blood Pressure, Pulse Rate, Oxygen Saturation, Body Temperature, and Respiration Rate), and 12-lead Electrocardiogram (ECG)
|
0 Participants
0
|
0 Participants
0
|
0 Participants
0
|
0 Participants
0
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Cmax= Maximum Concentration
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Cmax
Day 1
|
—
|
2045 nmol/L
Geometric Coefficient of Variation 57.39
|
—
|
1902 nmol/L
Geometric Coefficient of Variation 47.63
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Cmax
Day 28
|
—
|
1884 nmol/L
Geometric Coefficient of Variation 60.65
|
—
|
1730 nmol/L
Geometric Coefficient of Variation 63.54
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. tmax = Time to Maximum Concentration
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Tmax
Day 1
|
—
|
1.00 hour
Interval 0.5 to 4.0
|
—
|
1.00 hour
Interval 0.5 to 4.0
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Tmax
Day 28
|
—
|
1.00 hour
Interval 0.5 to 4.0
|
—
|
1.00 hour
Interval 0.5 to 2.0
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
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
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: t1/2 Lambda z
Day 1
|
—
|
3.801 hour
Geometric Coefficient of Variation 36.42
|
—
|
5.545 hour
Geometric Coefficient of Variation 58.67
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: t1/2 Lambda z
Day 28
|
—
|
5.331 hour
Geometric Coefficient of Variation 57.86
|
—
|
5.527 hour
Geometric Coefficient of Variation 64.06
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. AUClast= Area Under the Concentration-time Curve to the Last Measurable Concentration AUCinf = Area Under the Concentration-time Curve Extrapolated to Infinity AUCtau = Area Under the Concentration-time Curve Over a Dosing Interval AUCtau presented as AUC(0-24h) in the table. In line with standard PK analysis methodologies, AUCinf was estimated only for Day 1. AUClast and AUCtau were estimated for both Day 1 and Day 28.
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: AUClast, AUCinf, and AUCtau
AUClast: Day 1
|
—
|
7339 h*nmol/L
Geometric Coefficient of Variation 42.79
|
—
|
6052 h*nmol/L
Geometric Coefficient of Variation 32.89
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: AUClast, AUCinf, and AUCtau
AUClast: Day 28
|
—
|
7529 h*nmol/L
Geometric Coefficient of Variation 51.51
|
—
|
5482 h*nmol/L
Geometric Coefficient of Variation 34.29
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: AUClast, AUCinf, and AUCtau
AUCinf: Day 1
|
—
|
7409 h*nmol/L
Geometric Coefficient of Variation 42.88
|
—
|
6480 h*nmol/L
Geometric Coefficient of Variation 39.06
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: AUClast, AUCinf, and AUCtau
AUC0-24h: Day 1
|
—
|
7341 h*nmol/L
Geometric Coefficient of Variation 42.76
|
—
|
6112 h*nmol/L
Geometric Coefficient of Variation 32.58
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: AUClast, AUCinf, and AUCtau
AUC0-24h: Day 28
|
—
|
7301 h*nmol/L
Geometric Coefficient of Variation 48.45
|
—
|
5374 h*nmol/L
Geometric Coefficient of Variation 33.20
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. lambda z = Terminal elimination rate constant
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Lambda z
Day 1
|
—
|
0.1824 1/h
Geometric Coefficient of Variation 36.42
|
—
|
0.1250 1/h
Geometric Coefficient of Variation 58.67
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Lambda z
Day 28
|
—
|
0.1300 1/h
Geometric Coefficient of Variation 57.86
|
—
|
0.1254 1/h
Geometric Coefficient of Variation 64.06
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Vz/F = Apparent Volume of Distribution
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Vz/F
Day 1
|
—
|
215.8 L
Geometric Coefficient of Variation 44.25
|
—
|
360.0 L
Geometric Coefficient of Variation 44.45
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Vz/F
Day 28
|
—
|
307.2 L
Geometric Coefficient of Variation 84.33
|
—
|
432.8 L
Geometric Coefficient of Variation 68.96
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. CL/F = Apparent Clearance CLR = Renal Clearance
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: CL/F and CLR
CL/F: Day 28
|
—
|
39.95 L/h
Geometric Coefficient of Variation 48.45
|
—
|
54.27 L/h
Geometric Coefficient of Variation 33.20
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: CL/F and CLR
CLR: Day 1
|
—
|
8.492 L/h
Geometric Coefficient of Variation 231.5
|
—
|
16.41 L/h
Geometric Coefficient of Variation 35.30
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: CL/F and CLR
CLR: Day 28
|
—
|
11.13 L/h
Geometric Coefficient of Variation 75.23
|
—
|
17.05 L/h
Geometric Coefficient of Variation 194.2
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: CL/F and CLR
CL/F: Day 1
|
—
|
39.36 L/h
Geometric Coefficient of Variation 42.88
|
—
|
45.00 L/h
Geometric Coefficient of Variation 39.06
|
SECONDARY outcome
Timeframe: Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. TCP is calculated as the ratio of steady-state AUCtau (AUC0-24h) to first-dose AUCinf TCP = Temporal Change Parameter AUC = Area Under the Concentration-time Curve
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: TCP AUC
|
—
|
0.9853 Ratio
Geometric Coefficient of Variation 28.59
|
—
|
0.8293 Ratio
Geometric Coefficient of Variation 61.87
|
SECONDARY outcome
Timeframe: Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Rac AUC = AUC Accumulation Ratio; ratio of steady state AUCtau (AUC0-24h)/First Dose AUCtau (AUC0-24h) Rac Cmax = Cmax Accumulation Ratio; ratio of steady state Cmax/First Dose Cmax
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Rac AUC and Rac Cmax
Rac AUC: Day 28
|
—
|
0.9945 Ratio
Geometric Coefficient of Variation 28.76
|
—
|
0.8792 Ratio
Geometric Coefficient of Variation 54.94
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Rac AUC and Rac Cmax
Rac Cmax: Day 28
|
—
|
0.9212 Ratio
Geometric Coefficient of Variation 40.86
|
—
|
0.9095 Ratio
Geometric Coefficient of Variation 72.69
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Ae (0-24) = Cumulative Amount of Drug Excreted Unchanged in Urine
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Ae (0-24)
Day 1
|
—
|
22.53 mg
Geometric Coefficient of Variation 257.8
|
—
|
37.35 mg
Geometric Coefficient of Variation 33.89
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Ae (0-24)
Day 28
|
—
|
30.81 mg
Geometric Coefficient of Variation 95.26
|
—
|
26.89 mg
Geometric Coefficient of Variation 100.5
|
SECONDARY outcome
Timeframe: Day 1 and Day 28Population: PK analysis set: This included all participants who received AZD2389 and had at least one evaluable PK concentration
The PK of AZD2389 were evaluated following oral dosing in Cohort A and Cohort B and presented in table. Fe = Fraction of Dose Excreted Unchanged into Urine
Outcome measures
| Measure |
Cohort B - Placebo
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Fe (0-24)
Day 1
|
—
|
18.78 % of fraction of dose unchanged
Geometric Coefficient of Variation 257.8
|
—
|
31.12 % of fraction of dose unchanged
Geometric Coefficient of Variation 33.89
|
|
Plasma and Urine Pharmacokinetic (PK) Parameters of AZD2389: Fe (0-24)
Day 28
|
—
|
25.67 % of fraction of dose unchanged
Geometric Coefficient of Variation 95.26
|
—
|
22.41 % of fraction of dose unchanged
Geometric Coefficient of Variation 100.5
|
SECONDARY outcome
Timeframe: Day 28Population: Full analysis set: The Full Analysis Set consisted of all participants who were randomised and received at least at least one dose of study intervention
Effect of AZD2389 on plasma FAP activity following oral administration of AZD2389 in participants with chronic Liver Disease and hepatic fibrosis was evaluated and presented as percentage change from baseline in FAP activity. Percentage change when comparing post-treatment visits to baseline for each group, calculated as (Geometric LS mean - 1) \*100. FAP=Fibroblast Activating Protein
Outcome measures
| Measure |
Cohort B - Placebo
n=6 Participants
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
Cohort A - AZD2389
n=14 Participants
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
n=7 Participants
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 Participants
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
|---|---|---|---|---|
|
Inhibition of FAP Activity Calculated as Percentage Change in FAP Activity Against Baseline Compared to Placebo.
|
-10.3764 % of change in FAP activity
Interval -64.0341 to 123.3336
|
-80.0122 % of change in FAP activity
Interval -87.6644 to -67.6131
|
10.3140 % of change in FAP activity
Interval -43.5942 to 115.7436
|
-83.3455 % of change in FAP activity
Interval -91.2626 to -68.2546
|
Adverse Events
Cohort A - AZD2389
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Cohort A - Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Cohort B - AZD2389
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort B - Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort A - AZD2389
n=14 participants at risk
Participants with presumed Metabolic Dysfunction-associated Steatohepatitis (MASH)/Nonalcoholic Steatohepatitis (NASH) with fibrosis who received AZD2389.
|
Cohort A - Placebo
n=8 participants at risk
Participants with presumed MASH/NASH with fibrosis who received placebo.
|
Cohort B - AZD2389
n=12 participants at risk
Participants with underlying Steatotic Liver Diseases (SLDs) of varying aetiologies and advanced fibrosis including compensated cirrhosis who received AZD2389.
|
Cohort B - Placebo
n=6 participants at risk
Participants with underlying SLDs of varying aetiologies and advanced fibrosis including compensated cirrhosis who received placebo.
|
|---|---|---|---|---|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/14 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
8.3%
1/12 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Investigations
Electrocardiogram qt prolonged
|
0.00%
0/14 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
12.5%
1/8 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Nervous system disorders
Headache
|
7.1%
1/14 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Renal and urinary disorders
Dysuria
|
7.1%
1/14 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/14 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
12.5%
1/8 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.1%
1/14 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Gastrointestinal disorders
Diarrhoea
|
7.1%
1/14 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/14 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
16.7%
1/6 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/14 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
12.5%
1/8 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Infections and infestations
Gastroenteritis viral
|
7.1%
1/14 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Infections and infestations
Pneumonia
|
7.1%
1/14 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/14 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
12.5%
1/8 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.1%
1/14 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
7.1%
1/14 • Number of events 1 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/8 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/12 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
0.00%
0/6 • From screening to Day 35 up to 63 days
Includes adverse events with an onset date on or after the date of first dose of investigational product (IP) up to and including 7 days following the date of last IP dose.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator shall be entitled to publish the results of, or make presentations related to, the study provided that any publications or presentations to be made within 2 years after completion of the study shall require the sponsor's prior written consent.
- Publication restrictions are in place
Restriction type: OTHER