This trial is active, not recruiting.

Condition primary biliary cirrhosis
Treatments budesonide, budesonide placebo
Phase phase 3
Sponsor Dr. Falk Pharma GmbH
Start date February 2009
End date December 2015
Trial size 183 participants
Trial identifier NCT00746486, 2007-004040-70, BUC-56/PBC


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
One budesonide 3 mg capsule TD or one budesonide 3 mg capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d
One budesonide 3 mg capsule TD or one budesonide 3 mg capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d for 3 years
(Active Comparator)
One placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d
budesonide placebo
One placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d for 3 years

Primary Outcomes

Rate of patients without treatment failure after 3 years of treatment
time frame: 3 years, LOCF

Secondary Outcomes

course of pruritus
time frame: 3 years, LOCF
course of fatigue
time frame: 3 years, LOCF
course of Mayo Risk score
time frame: 3 years, LOCF
bone mineral density
time frame: 3 years, LOCF

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official 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
Principal investigator Raoul Poupon, Professor
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Dr. Falk Pharma GmbH.