Trial Outcomes & Findings for A Study to Test Whether BI 685509 Alone or in Combination With Empagliflozin Helps People With Liver Cirrhosis Caused by Viral Hepatitis or Non-alcoholic Steatohepatitis (NASH) Who Have High Blood Pressure in the Portal Vein (Main Vessel Going to the Liver) (NCT NCT05282121)

Last Updated: 2025-09-04

Results Overview

Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline (measured in millimetre of mercury \[mmHg\]) after 8 weeks of treatment is reported. Adjusted mean (Least Square Mean) was calculated using an analysis of covariance (ANCOVA) model without imputing the missing data. The model included treatment as fixed classification effects, and baseline HVPG as a linear covariate. The random error was assumed to be normally distributed with mean 0 and variance σ².

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

Before the first intake of trial medication (baseline), and after 8 weeks of treatment.

Results posted on

2025-09-04

Participant Flow

This randomised, open-label, parallel-group multinational phase II trial was conducted to investigate the effects of oral avenciguat (BI 685509) alone and in combination with empagliflozin on portal hypertension after 8 weeks treatment in patients with clinically significant portal hypertension (CSPH) in compensated cirrhosis.

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any entry criteria were violated.

Participant milestones

Participant milestones
Measure	Patients With HBV - Avenciguat Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With HCV - Avenciguat Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With or Without T2DM - Avenciguat Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With T2DM - Avenciguat + Empagliflozin Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.
Overall Study STARTED	14	13	38	25
Overall Study COMPLETED	12	10	30	22
Overall Study NOT COMPLETED	2	3	8	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Patients With HBV - Avenciguat Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With HCV - Avenciguat Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With or Without T2DM - Avenciguat Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With T2DM - Avenciguat + Empagliflozin Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.
Overall Study Adverse Event	1	1	4	1
Overall Study Study Terminated by Sponsor	1	2	2	2
Overall Study Other than listed	0	0	1	0
Overall Study No reason available	0	0	1	0

Baseline Characteristics

Treated set. Only patients with available HVPG measurements were included.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients With HBV - Avenciguat n=14 Participants Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With HCV - Avenciguat n=13 Participants Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With or Without T2DM - Avenciguat n=38 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With T2DM - Avenciguat + Empagliflozin n=25 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.	Total n=90 Participants Total of all reporting groups
Age, Continuous	49.9 Years STANDARD_DEVIATION 12.0 • n=14 Participants	60.3 Years STANDARD_DEVIATION 7.2 • n=13 Participants	62.6 Years STANDARD_DEVIATION 7.5 • n=38 Participants	64.1 Years STANDARD_DEVIATION 5.6 • n=25 Participants	60.7 Years STANDARD_DEVIATION 9.1 • n=90 Participants
Sex: Female, Male Female	0 Participants n=14 Participants	6 Participants n=13 Participants	23 Participants n=38 Participants	16 Participants n=25 Participants	45 Participants n=90 Participants
Sex: Female, Male Male	14 Participants n=14 Participants	7 Participants n=13 Participants	15 Participants n=38 Participants	9 Participants n=25 Participants	45 Participants n=90 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=14 Participants	4 Participants n=13 Participants	14 Participants n=38 Participants	14 Participants n=25 Participants	34 Participants n=90 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=14 Participants	9 Participants n=13 Participants	24 Participants n=38 Participants	11 Participants n=25 Participants	56 Participants n=90 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=14 Participants	0 Participants n=13 Participants	0 Participants n=38 Participants	0 Participants n=25 Participants	0 Participants n=90 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=14 Participants	0 Participants n=13 Participants	1 Participants n=38 Participants	0 Participants n=25 Participants	1 Participants n=90 Participants
Race (NIH/OMB) Asian	9 Participants n=14 Participants	0 Participants n=13 Participants	2 Participants n=38 Participants	2 Participants n=25 Participants	13 Participants n=90 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=14 Participants	0 Participants n=13 Participants	0 Participants n=38 Participants	0 Participants n=25 Participants	0 Participants n=90 Participants
Race (NIH/OMB) Black or African American	1 Participants n=14 Participants	0 Participants n=13 Participants	0 Participants n=38 Participants	0 Participants n=25 Participants	1 Participants n=90 Participants
Race (NIH/OMB) White	4 Participants n=14 Participants	13 Participants n=13 Participants	35 Participants n=38 Participants	23 Participants n=25 Participants	75 Participants n=90 Participants
Race (NIH/OMB) More than one race	0 Participants n=14 Participants	0 Participants n=13 Participants	0 Participants n=38 Participants	0 Participants n=25 Participants	0 Participants n=90 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=14 Participants	0 Participants n=13 Participants	0 Participants n=38 Participants	0 Participants n=25 Participants	0 Participants n=90 Participants
Hepatic Venous Pressure Gradient (HVPG)	13.68 millimetre of mercury (mmHg) STANDARD_DEVIATION 3.94 • n=14 Participants • Treated set. Only patients with available HVPG measurements were included.	12.10 millimetre of mercury (mmHg) STANDARD_DEVIATION 2.51 • n=13 Participants • Treated set. Only patients with available HVPG measurements were included.	15.46 millimetre of mercury (mmHg) STANDARD_DEVIATION 4.53 • n=37 Participants • Treated set. Only patients with available HVPG measurements were included.	15.28 millimetre of mercury (mmHg) STANDARD_DEVIATION 3.70 • n=24 Participants • Treated set. Only patients with available HVPG measurements were included.	14.63 millimetre of mercury (mmHg) STANDARD_DEVIATION 4.10 • n=88 Participants • Treated set. Only patients with available HVPG measurements were included.

PRIMARY outcome

Timeframe: Before the first intake of trial medication (baseline), and after 8 weeks of treatment.

Population: Full analysis set (FAS): this analysis set includes all enrolled or randomised patients who received at least one dose of trial medication and have a baseline measurement for the primary endpoint recorded.

Outcome measures

Outcome measures
Measure	Patients With HBV - Avenciguat n=14 Participants Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With HCV - Avenciguat n=13 Participants Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With or Without T2DM - Avenciguat n=37 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With T2DM - Avenciguat + Empagliflozin n=24 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.
Percentage Change in HVPG From Baseline (Measured in mmHg) After 8 Weeks of Treatment	-16.06 Percentage of change in HVPG Standard Error 6.66	-5.81 Percentage of change in HVPG Standard Error 7.09	3.83 Percentage of change in HVPG Standard Error 4.25	3.27 Percentage of change in HVPG Standard Error 5.08

SECONDARY outcome

Timeframe: Before the first intake of trial medication (baseline), and after 8 weeks of treatment.

Occurrence of a response, which is defined as \> 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatment is reported.

Outcome measures

Outcome measures
Measure	Patients With HBV - Avenciguat n=11 Participants Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With HCV - Avenciguat n=10 Participants Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With or Without T2DM - Avenciguat n=27 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With T2DM - Avenciguat + Empagliflozin n=19 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.
Occurrence of a Response, Which is Defined as > 10% Reduction From Baseline HVPG (Measured in mmHg) After 8 Weeks of Treatment	9 Count of participants	2 Count of participants	9 Count of participants	4 Count of participants

SECONDARY outcome

Timeframe: From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.

Population: Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.

Occurrence of one or more decompensation events (i.e. ascites, Variceal Haemorrhage \[VH\], and / or overt Hepatic Encephalopathy \[HE\]) during the 8-week treatment period is reported.

Outcome measures

Outcome measures
Measure	Patients With HBV - Avenciguat n=14 Participants Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With HCV - Avenciguat n=13 Participants Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With or Without T2DM - Avenciguat n=38 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With T2DM - Avenciguat + Empagliflozin n=25 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.
Occurrence of One or More Decompensation Events (i.e. Ascites, VH, and / or Overt HE) During the 8-week Treatment Period	1 Count of participants	0 Count of participants	4 Count of participants	1 Count of participants

SECONDARY outcome

Timeframe: From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.

Population: Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.

Occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 8-week treatment period is reported. The CTCAE grades are: 1 (mild Adverse Event \[AE\]), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).

Outcome measures

Outcome measures
Measure	Patients With HBV - Avenciguat n=14 Participants Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With HCV - Avenciguat n=13 Participants Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With or Without T2DM - Avenciguat n=38 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With T2DM - Avenciguat + Empagliflozin n=25 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.
Occurrence of CTCAE Grade 3 (or Higher) Hypotension or Syncope Based on Investigator Judgement, During the 8-week Treatment Period	0 Count of participants	0 Count of participants	0 Count of participants	1 Count of participants

SECONDARY outcome

Timeframe: From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks.

Population: Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.

Occurrence of discontinuation of treatment with avenciguat due to hypotension or syncope during the 8-week treatment period is reported.

Outcome measures

Outcome measures
Measure	Patients With HBV - Avenciguat n=14 Participants Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With HCV - Avenciguat n=13 Participants Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With or Without T2DM - Avenciguat n=38 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With T2DM - Avenciguat + Empagliflozin n=25 Participants Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.
Occurrence of Discontinuation Due to Hypotension or Syncope During the 8-week Treatment Period	0 Count of participants	0 Count of participants	0 Count of participants	1 Count of participants

Adverse Events

Patients With HBV - Avenciguat

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Patients With HCV - Avenciguat

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Patients With NASH With or Without T2DM - Avenciguat

Serious events: 6 serious events

Other events: 16 other events

Deaths: 0 deaths

Patients With NASH With T2DM - Avenciguat + Empagliflozin

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Patients With HBV - Avenciguat n=14 participants at risk Patients with Hepatitis B Virus (HBV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With HCV - Avenciguat n=13 participants at risk Patients with Hepatitis C Virus (HCV) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With or Without T2DM - Avenciguat n=38 participants at risk Patients with Non-Alcoholic Steatohepatitis (NASH) with or without type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment.	Patients With NASH With T2DM - Avenciguat + Empagliflozin n=25 participants at risk Patients with Non-Alcoholic Steatohepatitis (NASH) with type 2 Diabetes Mellitus (T2DM) were administered one film-coated tablet of avenciguat orally twice a day. The two doses were ideally taken at least 10 hours apart. The starting dose was 1 milligram (mg), which, if tolerated, was up-titrated to 2 mg one week later. If this dose was also tolerated, a second up-titration to 3 mg occured after another week. Patients remained on the highest dose for the remainder of the treatment period, until 8 weeks of treatment. Patients were additionally administered one 10 mg film-coated tablet of empagliflozin orally once a day.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/14 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/13 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	5.3% 2/38 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/25 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.
Gastrointestinal disorders Melaena	0.00% 0/14 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/13 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	2.6% 1/38 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/25 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/14 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/13 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	2.6% 1/38 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/25 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.
Infections and infestations Erysipelas	0.00% 0/14 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/13 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	2.6% 1/38 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/25 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.
Infections and infestations Herpes zoster	0.00% 0/14 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/13 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	2.6% 1/38 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/25 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer	0.00% 0/14 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	7.7% 1/13 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/38 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/25 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	7.1% 1/14 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/13 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/38 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/25 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/14 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	7.7% 1/13 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/38 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.	0.00% 0/25 • From first intake of study medication, until last intake of study medication plus 7 days, up to approximately 10 weeks (adverse events), or until end of study, up to 12 weeks (all-cause mortality). Treated set (TS): all patients who were enrolled or randomised to the trial medication and were treated with at least one dose of trial medication.

Other adverse events

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