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

Phase 3

Completed

Conditions: inflammation of the bile ducts of the liver
Primary Biliary Cirrhosis
10019654

Registration Number: NL-OMON33623

Lead Sponsor: Dr. Falk Pharma GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 6

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 (corresponding
to 312 U/L for women and 387 U/L for men) at any time since diagnosis of PBC
or
- ALT or AST * 2 times upper limit of normal (corresponding to 70 U/L for women
and 100 U/L for men) at inclusion or
- Total Bilirubin * 1.0 mg/dL 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 indirect immunofluorescence
8. Women of child-bearing potential have to apply appropriate contraceptive
methods, e.g., hormonal contraception, intrauterine device (IUD), doublebarrier
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.

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. alpha1-anti-Trypsin-deficiency
8. Haematochromatosis
9. Autoimmune-Hepatitis
10. Treatment with corticosteroids (except inhalative corticosteroids) within the last 2 months prior to inclusion and/or treatment with any of the following drugs
within the last 3 months prior to inclusion: colchicine, azathioprine or other
immunosuppressive drugs, 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
16. Albumin < 36 g/L
17. Prothrombin time < 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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Rate of patients without treatment failure after 3 years of treatment.<br /><br>Treatment failure is defined as:<br /><br>- death, or<br /><br>- registration on the liver transplant waiting list, or<br /><br>- cirrhosis defined by histology (staging according to Ludwig), or<br /><br>- presence of esophageal varices and/or ascites</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Normalisation of serum levels of AP<br /><br>- Improvement of serum levels of AP and bilirubin<br /><br>- Serum bilirubin levels more than 50 mol/L (3.0 mg/dl), or<br /><br>Fall in serum albumin count of 10% and to a value of less than 34 g/L<br /><br>- Course of pruritus (measured by VAS)<br /><br>- Course of fatigue (measured by PBC-40)<br /><br>- Course of Mayo Risk Score<br /><br>- Assessment of inflammatory activity2,3<br /><br>- Quality of Life by PBC-40<br /><br>- Global assessment of efficacy by patient and investigator<br /><br>- Fall in platelet counts to < 135.000/mm³<br /><br>- Fall in the prothrombin ratio of more than 25% and to a value of < 70%<br /><br>- Fibrosis marker (hyaluronic acid)<br /><br>- Doubling in the serum concentration of hyaluronic acid to more than 80 g/L<br /><br>or increase to a value of more than 100*g/L</p><br>