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

January 27, 2020 updated by: Dr. Falk Pharma GmbH

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75571
        • Hôpital Saint-Antoine
  • Germany
    • NRW
      • Bonn, NRW, Germany, 53105
        • Universitatsklinikum Bonn

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Rate of patients without treatment failure after 3 years of treatment
Time Frame: 3 years, LOCF
3 years, LOCF

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
course of pruritus
Time Frame: 3 years, LOCF
3 years, LOCF
course of fatigue
Time Frame: 3 years, LOCF
3 years, LOCF
course of Mayo Risk score
Time Frame: 3 years, LOCF
3 years, LOCF
bone mineral density
Time Frame: 3 years, LOCF
3 years, LOCF

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dr. Falk Pharma GmbH

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Raoul Poupon, Professor, Hôpital Saint-Antoine, 75571 Paris, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 3, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 4, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 28, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 27, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BUC-56/PBC
  • 2007-004040-70

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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