Portal hypertension, liver cirrhosis MedDRA version: 13.1 Level: PT Classification code 10036200 Term: Portal hypertension System Organ Class: 10019805 - Hepatobiliary disorders MedDRA version: 13.1 Level: LLT Classification code 10024667 Term: Liver cirrhosis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Name: Udenafil
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Udenafil
CAS Number: 268203-93-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number:
Sponsors
Dr. Falk Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent. 2. Man or woman between 18 and 70 years of age. 3. Compensated liver cirrhosis as proven by clinical findings, laboratory tests, and ultrasound. 4. Liver cirrhosis as proven by histology (histology within 5 years prior to Baseline visit) or FibroScan (facultative) or by unequivocal clinical, radiological and laboratory signs. 5. Clinically significant portal hypertension defined as HVPG = 12 mm Hg. 6. Low risk of bleeding characterized by no or small (=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Child-Pugh C. 2. Existing transjugular intrahepatic portosystemic shunt (TIPS) or surgical shunt. 3. Splenic or portal vein thrombosis by Doppler ultrasonography, magnetic resonance imaging. 4. Gastric/duodenal varices with bleeding stigmata (red colour sign or clot) or gastric/duodenal varices with history of bleeding. 5. Large oesophageal varices (= 5 mm in diameter). 6. Alcoholic hepatitis. 7. Hepatic encephalopathy = stage 2. 8. Ascites present at Baseline visit. 9. Total Bilirubin > 3 mg/dl. 10. Bleeding disorder, INR > 2. 11. Active peptic ulceration. 12. Positive HIV serology 13. Anatomical deformation of the penis or penile implants. 14. Predisposing priapism, sickle cell anaemia or trait, thrombocythaemia, polycythaemia, prone to venous thrombosis (immobility, surgery of pelvis, abdomen, hip, thrombophilia, history of thrombosis etc.), hyperviscosity syndrome (increased blood viscosity in particular due to polymers typical in multiple myeloma, polycythemia vera, Raynaud’s phenomenon, Waldenström’s macroglobulinemia). 15. Known hereditary degenerative retinal disorders, including retinitis pigmentosa. 16. Previous episode of NAION. 17. Renal failure (GFR 440 ms) or treatment with QTc interval-increasing medications. 19. Heart failure (NYHA II-IV). 20. Angina pectoris. 21. History of myocardial infarction, stroke or life-threatening arrhythmia. 22. Aortic stenosis. 23. Resting hypotension (systolic blood pressure [SBP]/diastolic blood pressure [DBP] 170/100 mm Hg). 24. Symptomatic hypotension (e.g. fainting) following alpha-blocker administration 25. Bacterial infection (positive blood, urine or ascites cultures; or ascites with leucocytes = 500/µl or PMN = 250/µl) within 2 weeks prior to Baseline visit. 26. Drugs that may have an effect on splanchnic haemodynamics/portal pressure, e.g. ß-blockers, clonidine, prazosin, nitrates, and any other antihypertensive treatment within 2 weeks prior to Baseline visit (Exception: losartan within 4 weeks prior to Baseline visit). 27. Concomitant treatment with ß-blockers, calcium channel blockers, clonidine, prazosin, nitrates, molsidomine, any antihypertensive treatment and any drug which may have an effect on splanchnic haemodynamics/portal pressure. 28. Concomitant treatment with vasopressin or somatostatin and their derivatives and analogues. 29. Concomitant treatment with platelet aggregation inhibitors, e.g. aspirin, heparin. 30. Concomitant treatment with other PDE-5 inhibitors, e.g. sildenafil, tadalafil or vardenafil. 31. Treatment with ketoconazole or other CYP3A inhibitors or inducers, consumption of grapefruit juice. 32. Active hepatocellular cancer or a history of hepatocellular cancer (to be excluded by ultrasound and tumour markers). 33. Active malignancy other than hepatocellular cancer or treatment with anticancer drugs during the last 5 years. Patients with a history of cancer other than hepatocellular cancer and at least five years of uneventful follow up and no signs of recurrence may be eligible. 34. Severe co-morbidity substantially reducing life expectancy. 35. Known intolerance/hypersensitivity/resistance to study drug or drugs of similar chemical structure or pharmacological profile. 36. Doubt about the patient’s cooperation, e.g. because of addiction to alcohol or drugs. 37. Existing or intended pregnancy or breast-feeding. 38. Participation in another clinical
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Hepatic venous pressure gradient (HVPG): Rate of response defined as final HVPG reduction to = 12 mm Hg or by = 20% compared to Baseline. HVPG (measurements to be performed in triplicate) determined pre-dose and one hour post-dose at Baseline, after one week, i.e. last day of pilot phase and after 1-week of treatment in the double-blind phase, and at the final/withdrawal visit of the double-blind phase. ;Main Objective: To assess the optimal dose of udenafil tablets for treatment of portal hypertension in patients with liver cirrhosis. ;Secondary Objective: To assess the safety and tolerability of a dose range of udenafil 12.5 to 75 mg/day administered for portal hypertension in patients with liver cirrhosis. | — |
Countries
Austria, Czech Republic, Germany, Lithuania
Outcome results
None listed