Phase 3 Study of Bezafibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis

NCT01654731 | Completed Phase 3 DMC

• 2 other identifiers: P100109AOM 10291
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that eventually leads to end-stage liver failure and death unless liver transplantation (LT) is performed. Ursodeoxycholic acid (UDCA) administered orally at the daily dose of 13-15 mg/kg is currently the only drug approved for the treatment of PBC. UDCA consistently improves biochemical liver tests, prolongs survival without LT, and delays histological progression as well as the occurrence of portal hypertension. However, a significant proportion (40%) of patients treated with UDCA shows an incomplete biochemical response and remains at high risk of death or LT. The development of new treatments in combination with UDCA is therefore needed. Several candidates exist among which is Bezafibrate. Bezafibrate belongs to the fibrates' pharmacological class, which has been developed 4 decades ago for the treatment of mixed hyperlipidaemia. Bezafibrate is cheap, widely available and well tolerated. There is now a substantial body of circumstantial evidence supporting that fibrates, and Bezafibrate in particular, are well tolerated and can improve biochemical liver tests in patients with PBC with incomplete response to UDCA. However, despite several positive successful pilot studies, there are still no phase 3 randomized placebo-controlled trials of fibrates for the treatment of PBC. The purpose of this protocol is therefore to conduct such a trial in a selected population of patients with PBC based on an incomplete biochemical response after 6 months of UDCA therapy.

Conditions

PBC

Keywords

PBC; Bezafibrate

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with complete biochemical response.

  The normalisation of hepatic biochemical tests (aminotransferases (AST, ALT), Alkaline Phosphatase, blood Albumin, blood bilirubin and prothrombin index).

  24 months

Secondary Outcomes (9)

• Percentage of patients having biological or clinical adverse reaction.

  24 months

• Percentage of patients having complete biochemical response.

  12 months

• Evolution of the pruritus.

  24 months

• Assessment of the fatigue and the quality of life.

  24 months

• Evolution of liver fibrosis surrogate markers.

  24 months

Study Arms (2)

Bezafibrate

EXPERIMENTAL

400 mg/Day

Drug: Bezafibrate

Placebo

PLACEBO COMPARATOR

1 tablet/ day

Drug: placebo

Interventions

Bezafibrate DRUG

Bezafibrate

placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Age \> 18
• Patient with PBC defined by 2 in 3 of the following criteria Positive antimitochondrial antibody type M2. Abnormal serum alkaline phosphatases (ALP \> 1,5N) and aminotransferase (AST or ALT \> 1N) activities.
• Histological hepatic injuries consistent with PBC from biopsy specimens of at least 10 mm.
• Patient treated with UDCA at the dose of 13 to 15 mg/kg/d (consistent to the AMM)
• Patients showing an incomplete biochemical response to UDCA as defined by : ALP \> 1,5N or AST \> 1,5N or total bilirubin \>17 µmol/l (with conjugated bilirubin \> 8 µmol/l) after ≥ 3 months of UDCA at the dose of 13 - 15 mg/kg/day.

You may not qualify if:

• Unsigned consent.
• Patient with no social insurance or having medical assistant of state
• Ascites or gastrointestinal bleeding (or history of these)
• Serum total bilirubinemia \> 50 μmols/L (3 mg/dl) (sample \< 3 months)
• Serum albuminemia \< 35 g/l (sample \< 3 months)
• Prothrombin index \< 70% (sample \< 3 months)
• Platelet count \< 100000/mm3 (sample \< 3 months)
• Treatment with corticosteroids, immunosuppressive agents, fibrates (or other PPAR-agonists) or statin in the last 3 months
• Any comorbidity susceptible to cause a hepatic impairment (HBV, HCV, or HIV seropositivity; excessive alcohol consumption; hemochromatosis, Wilson's disease, α1 antitrypsin deficiency; celiac disease; uncontrolled dysthyroidism; autoimmune hepatitis, inflammatory colitis)
• Any severe comorbidity decreasing life expectancy
• Intolerance or hypersensitivity to fibrates, to one of these components or other fibrates in general
• Known photosensitivity reaction to fibrates
• Pregnancy or desire of pregnancy
• Breast-feeding
• Renal failure (clearance of creatinine \< 60 ml/mn)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hepatology department - Hopital Saint Antoine

Paris, 75012, France

Location

Related Publications (2)

• Corpechot C, Chazouilleres O, Rousseau A, Le Gruyer A, Habersetzer F, Mathurin P, Goria O, Potier P, Minello A, Silvain C, Abergel A, Debette-Gratien M, Larrey D, Roux O, Bronowicki JP, Boursier J, de Ledinghen V, Heurgue-Berlot A, Nguyen-Khac E, Zoulim F, Ollivier-Hourmand I, Zarski JP, Nkontchou G, Lemoinne S, Humbert L, Rainteau D, Lefevre G, de Chaisemartin L, Chollet-Martin S, Gaouar F, Admane FH, Simon T, Poupon R. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis. N Engl J Med. 2018 Jun 7;378(23):2171-2181. doi: 10.1056/NEJMoa1714519.

  PMID: 29874528 BACKGROUND

• Corpechot C, Chazouilleres O, Lemoinne S, Rousseau A. Letter: reduction in projected mortality or need for liver transplantation associated with bezafibrate add-on in primary biliary cholangitis with incomplete UDCA response. Aliment Pharmacol Ther. 2019 Jan;49(2):236-238. doi: 10.1111/apt.15049. No abstract available.

  PMID: 30589964 DERIVED

Related Links

• Results

MeSH Terms

Interventions

Bezafibrate

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Benzoates; Acids, Carbocyclic; Chlorobenzoates; Phenyl Ethers; Ethers; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Officials

• Christophe Corpechot, Doctor

  Assistance Publique

  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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2012
• First Posted: August 1, 2012
• Study Start: October 15, 2012
• Primary Completion: December 31, 2016
• Study Completion: December 31, 2016
• Last Updated: February 27, 2023

Record last verified: 2023-02

Locations

FR (1)