PBC patients with an incomplete response to UDCA treatment defined by the failure to achieve s-AP levels < 1.5x upper limit of normal after at least 6 months of treatment with UDCA and with inflammatory activity in the histological assessment of the liver MedDRA version: 18.0 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 100000004871
Conditions
Interventions
Trade Name: Budenofalk 3mg
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: BUDESONIDE
CAS Number: 51333223
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
Dr. Falk Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent 2. Age = 18 years 3. UDCA treatment for at least 6 months prior to start of baseline examinations 4. Liver biopsy compatible with PBC and assessed with inflammatoryactivity according to the mHAI score, Ishak et al., 5. Liver biopsy performed within the last 6 months prior to start of baseline examinations 6. PBC patients with an incomplete response to UDCA treatment defined by the failure to achieve s-AP levels 1:40 by indirect immunofluorescence 8. Women of child-bearing potential have to apply appropriate contraceptive methods, e.g., hormonal contraception, intrauterine device (IUD), double-barrier method of contraception (e.g., use of a condom and spermicide), partner has undergone vasectomy and subject is in monogamous relationship. The investigator is responsible for determining whether the subject has adequate birth control for study participation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 114 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Histologically proven cirrhosis 2. Positive Hepatitis B or C serology 3. Positive HIV serology 4. Primary Sclerosing Cholangitis 5. Wilson's-Disease 6. Celiac Disease (if not controlled) 7. a1–anti-Trypsin-deficiency 8. Haemochromatosis 9. Autoimmune-Hepatitis (AIH; defined by an Alvarez score > 15 without treatment or = 17 with treatment); Note: PBC/AIH overlap disease, treated insufficiently with UDCA monotherapy may be enrolled 10. Treatment with corticosteroids (except inhalative corticosteroids) and immunosuppressants within the last 2 months prior to start of baseline examinations 11. Treatment with ketoconazole or other CYP3A inhibitors within the last 4 weeks before baseline; rifampicin (up to 600 mg/d) is allowed to treat pruritus until baseline 12. Sonographic or endoscopic signs of portal hypertension 13. Ascites or history of ascites 14. Hepatic encephalopathy or history of hepatic encephalopathy 15. Cataract 16. Albumin 125 mg/dl on an empty stomach), even when controlled 21. Hypertension, defined as persistent raised blood pressure > 140/90 mmHg 22. Suspected non-compliance of the patient (suspected difficulties to comply with the study period of 36 months) 23. Severe co-morbidity substantially reducing life expectancy 24. Known intolerance/hypersensitivity/resistance to study drugs or drugs of similar chemical structure or pharmacological profile 25. Existing or intended pregnancy or breast-feeding 26. Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation (i.e. having received the trial medication) in this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To compare the efficacy and tolerability of a combination therapy with ursodeoxycholic acid (12-16 mg/kg body weight/d) plus budesonide (9 mg/d) vs. ursodeoxycholic acid (12-16 mg/kg body weight/d) plus placebo in the treatment of PBC. ;Secondary Objective: - To study safety and tolerability in the form of adverse events and laboratory parameters. - To assess patients’ Quality of Life. ;Primary end point(s): Rate of patients with improvement of liver histology with respect to inflammation (an improvement by at least 3 points in the mHAI sum score or no inflammatory activity according to Ishak et al., 1995) and no progression of fibrosis (staging according to the Ludwig) compared to baseline at the individual last patient visit within the study;Timepoint(s) of evaluation of this end point: after 3 years of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Rate of patients presenting with cirrhosis or esophageal varices and/or ascites at the end of treatment or patients registered on the liver waiting transplant list or patients with liver related death during up to 3 years of treatment - Rate of patients with improvement of liver histology with respect to stage - Rate of patients with improvement of liver histology with respect to grade and stage - Normalisation of serum levels of AP or reduction of baseline AP levels by at least 40 %, - Improvement of serum levels of AP and bilirubin - other ;Timepoint(s) of evaluation of this end point: after 3 years of treatment | — |
Countries
Austria, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Lithuania, Netherlands, Poland, Spain, Sweden, United Kingdom
Contacts
Public ContactProject Management
Dr. Falk Pharma GmbH
Outcome results
None listed