Double-blind, randomised, placebo-controlled, multi-centre phase III clinical study comparing the combination of ursodeoxycholic acid capsules plus budesonide capsules to ursodeoxycholic acid capsules plus placebo in the treatment of primary biliary cirrhosis - Ursodeoxycholic acid plus budesonide vs. ursodeoxycholic acid alone in PBC

• Register: EUCTR
• Last refreshed on: 10 July 2012
• Main ID: EUCTR2007-004040-70-FR
• Date of registration: 09/06/2008
• Prospective Registration: Yes
• Primary sponsor: Dr. Falk Pharma GmbH
• Public title: Double-blind, randomised, placebo-controlled, multi-centre phase III clinical study comparing the combination of ursodeoxycholic acid capsules plus budesonide capsules to ursodeoxycholic acid capsules plus placebo in the treatment of primary biliary cirrhosis - Ursodeoxycholic acid plus budesonide vs. ursodeoxycholic acid alone in PBC
• Scientific title: Double-blind, randomised, placebo-controlled, multi-centre phase III clinical study comparing the combination of ursodeoxycholic acid capsules plus budesonide capsules to ursodeoxycholic acid capsules plus placebo in the treatment of primary biliary cirrhosis - Ursodeoxycholic acid plus budesonide vs. ursodeoxycholic acid alone in PBC
• Date of first enrolment: 09/09/2008
• Target sample size: 183
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004040-70
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Denmark, Finland, France, Germany, Hungary, Italy, Lithuania, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent
2. Age = 18 years
3. UDCA treatment for at least 6 months prior to inclusion
4. Liver biopsy compatible with PBC
5. Liver biopsy performed within the last 6 months prior to inclusion
6. PBC patients at risk of disease progression based on one or more of the following criteria:
- Serum alkaline phosphatase = 3 times the upper limit of normal at any time since diagnosis of PBC and ALT = 2 times upper limit of normal or
- Total Bilirubin = 1.0 mg/dl (= 17 µmol/L) or
- Moderate to severe periportal or periseptal lymphocytic interface hepatitis or- Periportal and portal fibrosis with numerous septa (Ludwig stage III) without cirrhosis
7. Type 2 anti-mitochondrial antibodies > 1:40 by direct 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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 (blood tests and/or oesophago-gastro-duodenoscopy with histological examination to be performed)
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 any of the following drugs within the last 3 months prior to inclusion: colchicine, corticosteroids, azathioprine or other immunosuppressive drugs (e.g. cyclosporine, methotrexate), chlorambucil, D-penicillamine, fibrates, or antihyperlipidemic drugs
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. Total bilirubin > 3.0 mg/dl (> 50 µmol/L)
16. Albumin < 36 g/L
17. Prothrombin ratio < 70%
18. Platelet count < 135.000/mm3
19. Osteoporosis proven by bone densitometry
20. Diabetes mellitus, defined as B-Glucose > 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 in this trial


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with Primary Biliary Cirrhosis at risk of disease progression
MedDRA version: 9.1 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis

Intervention(s)

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
Concentration number: 3-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Ursofalk
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: URSODEOXYCHOLIC ACID
CAS Number: 128132
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

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.

- 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 without treatment failure after 3 years of treatment. Treatment failure is defined as:
· Death, or
· Registration on the liver transplant waiting list, or
· Cirrhosis defined by histology (staging according to Ludwig), or
· Presence of esophageal varices and/or ascites

Secondary Objective:

Secondary ID(s)

BUC-56/PBC

2007-004040-70-DE