Study to compare the combination of ursodeoxycholic acid and budesonide with the combination of ursodeoxycholic acid and placebo in the treatment of primary biliary cirrhosis

• Register: EUCTR
• Last refreshed on: 25 January 2016
• Main ID: EUCTR2007-004040-70-DE
• Date of registration: 14/03/2008
• Prospective Registration: Yes
• Primary sponsor: Dr. Falk Pharma GmbH
• Public title: Study to compare the combination of ursodeoxycholic acid and budesonide with the combination of ursodeoxycholic acid and placebo in the treatment of primary biliary cirrhosis
• Scientific 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 - Ursodeoxycholic acid plus budesonide vs. ursodeoxycholic acid alone in PBC
• Date of first enrolment: 15/05/2008
• Target sample size: 144
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004040-70
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: an adaptive 2 stage group-sequential design with an interim analysis If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Lithuania, Netherlands, Poland, Spain, Sweden, United Kingdom

Contacts

• Name: Project Management
• Affiliation: Dr. Falk Pharma GmbH

• Name: Project Management
• Affiliation: Dr. Falk Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent
2. Age = 18 years
3. UDCA treatment for at least 6 months prior to start of baseline examinations
4. Liver biopsy compatible with PBC and assessed with inflammatoryactivity according to the mHAI score, Ishak et al.,
5. Liver biopsy performed within the last 6 months prior to start of baseline examinations
6. PBC patients with an incomplete response to UDCA treatment defined by the failure to achieve s-AP levels < 1.5x upper limit of normal after at least 6 months of treatment with UDCA and with inflammatory activity according to the mHAI sum score (Ishak et al., 1995) in the histological assessment of the liver
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), 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 114
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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. 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 corticosteroids (except inhalative corticosteroids) and immunosuppressants within the last 2 months prior to start of baseline examinations
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. Cataract
16. Albumin < 36 g/L
17. Prothrombin time < 70% , or if prothrombin time (%) not available, prothrombin ratio (INR) out of normal range and clinically significant
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 (i.e. having received the trial medication) in this trial


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

PBC patients with an incomplete response to UDCA treatment defined by the failure to achieve s-AP levels < 1.5x upper limit of normal after at least 6 months of treatment with UDCA and with inflammatory activity in the histological assessment of the liver
MedDRA version: 18.0 Level: LLT Classification code 10036680 Term: Primary biliary cirrhosis System Organ Class: 100000004871

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Budenofalk 3mg
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: BUDESONIDE
CAS Number: 51333223
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Ursofalk
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: URSODEOXYCHOLIC ACID
CAS Number: 128132
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: after 3 years of treatment

Secondary Objective: - To study safety and tolerability in the form of adverse events and laboratory parameters.

- To assess patients’ Quality of Life.

Main Objective: - To compare the efficacy and tolerability of a combination therapy with ursodeoxycholic acid (12-16 mg/kg body weight/d) plus budesonide (9 mg/d) vs. ursodeoxycholic acid (12-16 mg/kg body weight/d) plus placebo in the treatment of PBC.

Primary end point(s): Rate of patients with improvement of liver histology with respect to inflammation (an improvement by at least 3 points in the mHAI sum score or no inflammatory activity according to Ishak et al., 1995) and no progression of fibrosis (staging according to the Ludwig) compared to baseline at the individual last patient visit within the study

Secondary Outcome(s)

Secondary end point(s): - Rate of patients presenting with cirrhosis or esophageal varices and/or ascites at the end of treatment or patients registered on the liver waiting transplant list or patients with liver related death during up to 3 years of treatment
- Rate of patients with improvement of liver histology with respect to stage
- Rate of patients with improvement of liver histology with respect to grade and stage
- Normalisation of serum levels of AP or reduction of baseline AP levels by at least 40 %,
- Improvement of serum levels of AP and bilirubin
- other

Timepoint(s) of evaluation of this end point: after 3 years of treatment

Secondary ID(s)

NCT00746486

BUC-56/PBC

Source(s) of Monetary Support

Dr. Falk Pharma GmbH