Overview
Ursodeoxycholic Acid Plus Budesonide Versus Ursodeoxycholic Acid Alone in Primary Biliary Cirrhosis (PBC)
Status:
Terminated
Terminated
Trial end date:
2019-10-01
2019-10-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
The study is aimed to compare the efficacy and tolerability of a combination therapy with ursodeoxycholic acid (12-16 mg/kg body weight (BW)/d) plus budesonide (9 mg/d) vs. ursodeoxycholic acid (12-16 mg/kg BW/d) plus placebo in the treatment of PBC. Depending on ALT values 6 mg/d budesonide are allowed. The study population will be patients with PBC at risk for disease progression. It is assumed that the combination therapy will result in a decrease of treatment failures after 3 years of treatment.Phase:
Phase 3Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Dr. Falk Pharma GmbHTreatments:
Budesonide
Ursodeoxycholic Acid
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
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. α1-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