Ursodeoxycholic Acid Plus Budesonide Versus Ursodeoxycholic Acid Alone in Primary Biliary Cirrhosis (PBC)

Primary Biliary Cirrhosis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00746486
• Other study ID #: BUC-56/PBC
• Secondary ID: 2007-004040-70
• Status: Terminated
• Phase: Phase 3
• Start date: February 2009
• Est. completion date: October 2019

Study information

• Verified date: January 2020
• Source: Dr. Falk Pharma GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 62
• Est. completion date: October 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. 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

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis
• Liver Cirrhosis, Biliary
• Primary Biliary Cirrhosis

Intervention

Drug:
• budesonide
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
• budesonide placebo
One placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d for 3 years

Locations

Country	Name	City	State
France	Hôpital Saint-Antoine	Paris
Germany	Universitätsklinikum Bonn	Bonn	NRW

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Falk Pharma GmbH

Countries where clinical trial is conducted

France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of patients without treatment failure after 3 years of treatment		3 years, LOCF
Secondary	course of pruritus		3 years, LOCF
Secondary	course of fatigue		3 years, LOCF
Secondary	course of Mayo Risk score		3 years, LOCF
Secondary	bone mineral density		3 years, LOCF