Primary Biliary CirrhosisPhase 3NCT00746486
Ursodeoxycholic Acid Plus Budesonide Versus Ursodeoxycholic Acid Alone in Primary Biliary Cirrhosis (PBC)
A Phase 3 study testing budesonide in people with Primary Biliary Cirrhosis, run by Dr. Falk Pharma GmbH at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- budesonide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Feb 2009to Oct 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent
- Age ≥ 18 years
- UDCA treatment for at least 6 months prior to inclusion
- Liver biopsy compatible with PBC
- Liver biopsy performed within the last 6 months prior to inclusion
- PBC patients at risk of disease progression based on one or more of the following criteria:
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- 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
Who cannot join
- 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)
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- 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 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
- 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
- Prothrombin ratio < 70%
- Platelet count < 135.000/mm3
- Osteoporosis proven by bone densitometry
- Diabetes mellitus, defined as B-Glucose > 125 mg/dl on an empty stomach (even when controlled)
- Hypertension, defined as persistent raised blood pressure > 140/90 mmHg
- Suspected non-compliance of the patient (suspected difficulties to comply with the study period of 36 months)
- Severe co-morbidity substantially reducing life expectancy
- Known intolerance/hypersensitivity/resistance to study drugs or drugs of similar chemical structure or pharmacological profile
- Existing or intended pregnancy or breast-feeding
- Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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
- Being tested
- budesonide, budesonide placebo
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
budesonideDrug
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
budesonide placeboDrug
One placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d for 3 years
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | One budesonide 3 mg capsule TD or one budesonide 3 mg capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d Receives: Drug: budesonide |
| B | Active comparator | One placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d Receives: Drug: budesonide placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of patients without treatment failure after 3 years of treatment
Measured: 3 years, LOCF
Secondary outcomes (4)
course of pruritus
Measured: 3 years, LOCF
course of fatigue
Measured: 3 years, LOCF
course of Mayo Risk score
Measured: 3 years, LOCF
bone mineral density
Measured: 3 years, LOCF
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2008 (estimated)
- Study startFeb 2009
- Primary completionOct 2019
- Study completionOct 2019
Why it stopped: Study stopped based on the recommendation of the IDMC after a planned Interim Analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Primary Biliary CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Falk Pharma GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Raoul Poupon, Professor, Principal investigator, Hôpital Saint-Antoine, 75571 Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00746486
- Sponsor's protocol ID
- BUC-56/PBC
- Other IDs
- 2007-004040-70
- Status last verified
- Jan 2020
- First submitted
- 3 Sep 2008
- Last updated
- 28 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 32950590Mousa 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.
PubMed 25543678
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00746486
- Acronym / sponsor ID
- BUC-56/PBC
- Conditions
- Primary Biliary Cirrhosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped based on the recommendation of the IDMC after a planned Interim Analysis
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Dr. Falk Pharma GmbHIndustry (pharma, biotech, devices)
- Study start
- Feb 2009
- Primary completion
- Oct 2019 (actual)
- Study completion
- Oct 2019 (actual)
- First posted
- 4 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: budesonideOne budesonide 3 mg capsule TD or one budesonide 3 mg capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d |
| B | Active comparator | Drug: budesonide placeboOne placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Signed informed consent
- Age ≥ 18 years
- UDCA treatment for at least 6 months prior to inclusion
- Liver biopsy compatible with PBC
- Liver biopsy performed within the last 6 months prior to inclusion
Key exclusion criteria (26 listed)
- Histologically proven cirrhosis
- Positive Hepatitis B or C serology
- Positive HIV serology
- Primary Sclerosing Cholangitis
- Wilson's-Disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| budesonideOne budesonide 3 mg capsule TD or one budesonide 3 mg capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d for 3 years | Drug | A |
| budesonide placeboOne placebo capsule TD or One placebo capsule BD and 12-16 mg ursodeoxycholic acid/kg BW/d for 3 years | Drug | B |
Primary outcome
Rate of patients without treatment failure after 3 years of treatment
Time frame: 3 years, LOCF
4 secondary outcomes
course of pruritus
Time frame: 3 years, LOCF
course of fatigue
Time frame: 3 years, LOCF
course of Mayo Risk score
Time frame: 3 years, LOCF
bone mineral density
Time frame: 3 years, LOCF
Results and safety
The study was stopped early (reason given: Study stopped based on the recommendation of the IDMC after a planned Interim Analysis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2020.
- Derived from this study: PubMed 32950590Hirschfield 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.
- Derived from this study: PubMed 25543678Mousa 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raoul Poupon, Professor principal investigator
Hôpital Saint-Antoine, 75571 Paris, France
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing budesonide in people with Primary Biliary Cirrhosis, run by Dr. Falk Pharma GmbH at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study stopped based on the recommendation of the IDMC after a planned Interim Analysis). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of patients without treatment failure after 3 years of treatment (time frame: 3 years, LOCF). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00746486, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2020.