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

NCT00746486 | Terminated Phase 3

• 2 other identifiers: BUC-56/PBC2007-004040-70
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Primary Biliary Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Rate of patients without treatment failure after 3 years of treatment

  3 years, LOCF

Secondary Outcomes (4)

• course of pruritus

  3 years, LOCF

• course of fatigue

  3 years, LOCF

• course of Mayo Risk score

  3 years, LOCF

• bone mineral density

  3 years, LOCF

Study Arms (2)

A

EXPERIMENTAL

One budesonide 3 mg capsule TD or one budesonide 3 mg capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d

Drug: budesonide

B

ACTIVE COMPARATOR

One placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d

Drug: budesonide placebo

Interventions

budesonide DRUG

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

A

budesonide placebo DRUG

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

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Age ≥ 18 years
• Liver biopsy compatible with PBC
• 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
• Type 2 anti-mitochondrial antibodies \> 1:40 by direct immunofluorescence
• 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

You may not qualify if:

• Histologically proven cirrhosis
• Positive Hepatitis B or C serology
• Positive HIV serology
• Primary Sclerosing Cholangitis
• Wilson's-Disease
• Celiac Disease (blood tests and/or oesophago-gastro-duodenoscopy with histological examination to be performed)
• α1-anti-Trypsin-deficiency
• Haemochromatosis
• 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
• 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
• Sonographic or endoscopic signs of portal hypertension
• Ascites or history of ascites
• Hepatic encephalopathy or history of hepatic encephalopathy
• Total bilirubin \> 3.0 mg/dl (\> 50 µmol/L)
• Albumin \< 36 g/L

Sponsors & Collaborators

• Dr. Falk Pharma GmbH: lead

Study Sites (2)

Hôpital Saint-Antoine

Paris, 75571, France

Location

Universitätsklinikum Bonn

Bonn, North Rhine-Westphalia, 53105, Germany

Location

Related Publications (2)

• Hirschfield GM, Beuers U, Kupcinskas L, Ott P, Bergquist A, Farkkila M, Manns MP, Pares A, Spengler U, Stiess M, Greinwald R, Prols M, Wendum D, Drebber U, Poupon R. A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA. J Hepatol. 2021 Feb;74(2):321-329. doi: 10.1016/j.jhep.2020.09.011. Epub 2020 Sep 17.

  PMID: 32950590 DERIVED

• Mousa HS, Lleo A, Invernizzi P, Bowlus CL, Gershwin ME. Advances in pharmacotherapy for primary biliary cirrhosis. Expert Opin Pharmacother. 2015 Apr;16(5):633-43. doi: 10.1517/14656566.2015.998650. Epub 2014 Dec 29.

  PMID: 25543678 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Raoul Poupon, Professor

  Hôpital Saint-Antoine, 75571 Paris, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2008
• First Posted: September 4, 2008
• Study Start: February 1, 2009
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: January 28, 2020

Record last verified: 2020-01

Locations

DE (1); FR (1)