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

Condition(s) targeted: Primary Biliary Cirrhosis

Intervention: budesonide (Drug); budesonide placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Dr. Falk Pharma GmbH

Official(s) and/or principal investigator(s):
Raoul Poupon, Professor, Principal Investigator, Affiliation: Hôpital Saint-Antoine, 75571 Paris, France

Overall contact:
Markus Proels, PhD, Phone: *49 761 1514, Ext: 199, Email: proels@drfalkpharma.de

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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Rate of patients without treatment failure after 3 years of treatment

Secondary outcome:

course of pruritus

course of fatigue

course of Mayo Risk score

bone mineral density

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Markus Proels, PhD, Phone: *49 761 1514, Ext: 199, Email: proels@drfalkpharma.de

Hôpital Saint-Antoine, Paris 75571, France; Not yet recruiting
Raoul Poupon, Professor, Principal Investigator

Universitätsklinikum Bonn, Bonn, NRW 53105, Germany; Recruiting
Ulrich Spengler, Professor, Principal Investigator

Starting date: September 2008
Ending date: September 2013
Last updated: July 24, 2009