Health Condition 1: K766- Portal hypertension
Conditions
Interventions
Intervention1: BI 685509: 2 mg and 3 mg BI 685509 film-coated tablets will be given orally twice daily
and duration of treatment will be 24 weeks
Control Intervention1: Placebo matching BI 685509: Pl
Sponsors
Boehringer Ingelheim International GmbH
PAREXEL International Clinical Research Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1) Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial 2) Male or female who is greater than or equal to 18 (or who is of legal age in countries where that is greater than 18) and less than or equal to 75 years old at screening 3) Clinical signs of Clinically Significant Portal Hypertension (CSPH) as described by either one of the points below. Each trial patient must have a gastroscopy during the screening period or within 3 months prior to screening 4) Documented endoscopic proof of oesophageal varices and / or gastric varices at screening or within 3 months prior to screening 5) Documented endoscopic-treated oesophageal varices as preventative treatment 6) CSPH defined as baseline Hepatic Venous Pressure Gradient (HVPG) greater than or equal to 10 mmHg, based on a local interpretation of the pressure tracing 7) Diagnosis of compensated alcohol-related cirrhosis. Diagnosis must be based on histology (historical data is acceptable) or on clinical evidence of cirrhosis (e.g. platelet count less than 150 x 10 9/L [150 x 10 3/µL], nodular liver surface on imaging or splenomegaly) 8) Abstinence from alcohol for a minimum of 2 months prior to screening, which, based on Investigator judgement, can be maintained throughout the trial (both evaluated based on Investigator judgement) 9) Willing and able to undergo HVPG measurements per protocol (based on Investigator judgement) 10) if receiving statins, Non-Selective Beta-Blockers (NSBBs) or carvedilol must be on a stable dose for at least 3 months prior to screening, with no planned dose change throughout the trial Further inclusion criteria apply
Exclusion criteria
Exclusion criteria: 1) Previous clinically significant decompensation events (e.g. ascites [more than perihepatic ascites], Variceal Haemorrhage (VH) and / or apparent Hepatic Encephalopathy (HE)) 2) History of other forms of chronic liver disease (e.g. non alcoholic steatohepatitis (NASH), Hepatitis B virus (HBV), untreated Hepatitis C Virus (HCV), autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilsons disease, haemachromatosis, alpha 1 antitrypsin (A1At) deficiency) 3) Alcohol Related Liver Disease (ARLD) without adequate treatment (e.g. lifestyle modification) or with ongoing pathological drinking behaviour (misuse or abuse based on Investigator judgement) 4) Systolic Blood Pressure (SBP) less than 100 mmHg and Diastolic Blood Pressure (DBP) less than 70 mmHg at screening 5) Model of End stage Liver Disease (MELD) score of greater than 15 at screening, calculated by the central laboratory 6) Hepatic impairment defined as a Child Turcotte Pugh score greater than or equal to B8 at screening, calculated by the site, using central laboratory results 7) Alanine amino transferase (ALT) or Aspartate amino transferase (AST) greater than 5 times upper limit of normal (ULN) at screening 8) Estimated Glomerular Filtration Rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) less than 20 mL/min/1.73 m2 at screening 9) Alpha fetoprotein greater than 50 ng/mL (greater than 50 µg/L) at screening 10) History of clinically relevant orthostatic hypotension, fainting spells or blackouts due to hypotension or of unknown origin (based on Investigator judgement) Further exclusion criteria apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage change in Hepatic Venous Pressure Gradient (HVPG) from baseline (measured in mmHg) after 24 weeks of treatmentTimepoint: at baseline, at week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the first 8 weeks of the treatment periodTimepoint: up to 8 weeks;Occurrence of CTCAE grade 3 (or higher) hypotension or syncope based on Investigator judgement, during the 24 week treatment periodTimepoint: up to 24 weeks;Occurrence of discontinuation due to hypotension or syncope during the 24 week treatment periodTimepoint: up to 24 weeks;Occurrence of discontinuation due to hypotension or syncope during the first 8 weeks of the treatment periodTimepoint: up to 8 weeks;Occurrence of one or more decompensation events (i.e. ascites, Variceal Haemorrhage (VH), and/or overt Hepatic Encephalopathy (HE)) during the 24 week treatment periodTimepoint: up to 24 weeks;Percentage change in HVPG from baseline (measured in mmHg) after 8 weeks of treatmentTimepoint: at baseline, at week 8;Response defined as less than 10% reduction from baseline HVPG (measured in mmHg) after 24 weeks of treatmentTimepoint: at baseline, at week 24;Response defined as less than 10% reduction from baseline HVPG (measured in mmHg) after 8 weeks of treatmentTimepoint: at baseline, at week 8 | — |
Countries
Argentina, Austria, Belgium, Canada, China, Croatia, Denmark, France, Germany, India, Israel, Italy, Japan, Netherlands, Portugal, Republic of Korea, Romania, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States of America
Contacts
Public ContactDr Annappa Kamath
PAREXEL International Clinical Research Private Limited
Outcome results
None listed