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

This study is currently recruiting participants.
Verified September 2013 by Dr. Falk Pharma GmbH
Sponsor:
Information provided by (Responsible Party):
Dr. Falk Pharma GmbH
ClinicalTrials.gov Identifier:
NCT00746486
First received: September 3, 2008
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Primary Biliary Cirrhosis
Drug: budesonide
Drug: budesonide placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: 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

Resource links provided by NLM:


Further study details as provided by Dr. Falk Pharma GmbH:

Primary Outcome Measures:
  • Rate of patients without treatment failure after 3 years of treatment [ Time Frame: 3 years, LOCF ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • course of pruritus [ Time Frame: 3 years, LOCF ] [ Designated as safety issue: No ]
  • course of fatigue [ Time Frame: 3 years, LOCF ] [ Designated as safety issue: No ]
  • course of Mayo Risk score [ Time Frame: 3 years, LOCF ] [ Designated as safety issue: No ]
  • bone mineral density [ Time Frame: 3 years, LOCF ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 183
Study Start Date: February 2009
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
One budesonide 3 mg capsule TD or one budesonide 3 mg capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d
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
Active Comparator: B
One placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d
Drug: budesonide placebo
One placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d for 3 years

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00746486

Contacts
Contact: Markus Proels, PhD *49 761 1514 ext 199 proels@drfalkpharma.de

Locations
France
Hôpital Saint-Antoine Not yet recruiting
Paris, France, 75571
Principal Investigator: Raoul Poupon, Professor         
Germany
Universitätsklinikum Bonn Recruiting
Bonn, NRW, Germany, 53105
Principal Investigator: Ulrich Spengler, Professor         
Sponsors and Collaborators
Dr. Falk Pharma GmbH
Investigators
Principal Investigator: Raoul Poupon, Professor Hôpital Saint-Antoine, 75571 Paris, France
  More Information

No publications provided

Responsible Party: Dr. Falk Pharma GmbH
ClinicalTrials.gov Identifier: NCT00746486     History of Changes
Other Study ID Numbers: BUC-56/PBC, 2007-004040-70
Study First Received: September 3, 2008
Last Updated: September 25, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Sweden: Medical Products Agency
Finland: Finnish Medicines Agency
Hungary: National Institute of Pharmacy

Additional relevant MeSH terms:
Liver Cirrhosis, Biliary
Liver Cirrhosis
Fibrosis
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Pathologic Processes
Ursodeoxycholic Acid
Budesonide
Cholagogues and Choleretics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 15, 2014