Liver Cirrhosis, BiliaryPhase 2NCT00550862
Study of INT 747 in Combination With URSO in Patients With Primay Biliary Cirrhosis (PBC)
A Phase 2 study testing INT-747 and Ursodeoxycholic Acid (URSO) in people with Liver Cirrhosis, Biliary, run by Intercept Pharmaceuticals at 32 sites in 8 countries.
Trial summary
The primary hypothesis is that INT-747 will cause a reduction in alkaline phosphatase levels in Primary Biliary Cirrhosis patients, over a 12 week treatment period, as compared to placebo. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Cirrhosis, Biliary
- What is being tested?
- INT-747 and Ursodeoxycholic Acid (URSO)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 165 participants
- Where
- 32 sitesin 8 countries
- Study dates
- Oct 2007to Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female age 18 to 70 years.
- Stable dose of ursodeoxycholic acid (URSO, UDCA) for at least 6 months prior to screening.
- Female patients must be postmenopausal, surgically sterile, or prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of dosing.
- Male patients must be prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of the dosing.
- Proven or likely PBC, as demonstrated by the patient presenting with at least 2 of the following 3 diagnostic factors:
- History of increased AP levels for at least 6 months prior to Day 0
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- Positive AMA titer (>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive)
- Liver biopsy consistent with PBC.
- Screening AP value between 1.5 and 10 × ULN.
Who cannot join
- Administration of the following drugs at any time during the 3 months prior to screening for the study: colchicine, methotrexate, azathioprine, or systemic corticosteroids.
- Screening conjugated (direct) bilirubin >2 × ULN.
- Screening ALT or AST >5 × ULN.
- Screening serum creatinine >1.5 mg/dL (133 mol/L).
- History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).
- History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HCV, HBV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease, definite autoimmune liver disease or biopsy proven nonalcoholic steatohepatitis (NASH).
- Pregnancy.
Trial locations and contacts
32 sites in 8 countries.
32 sites in 8 countries
United States13 sites
Tufts Medical Center
Boston, Massachusetts, 02111
Cleveland Clinic
Cleveland, Ohio, 44195
UT Southwestern Medical Center
Dallas, Texas, 75390
U Florida Hepatology
Gainesville, Florida, 32610
Baylor College of Medicine
Houston, Texas, 77030
University of Miami - Center for Liver Diseases
Miami, Florida, 33136
Beth Israel Medical Center
New York, New York, 10003
Mt. Sinai School of Medicine
New York, New York, 10029
Henry Ford Health Center Columbus
Novi, Michigan, 48377
McGuire DVAMC
Richmond, Virginia, 23249
Mayo Clinic
Rochester, Minnesota, 555905
Virginia Mason Medical Center
Seattle, Washington, 98101
Saint Louis University
St Louis, Missouri, 63104
Canada5 sites
University of Calgary
Calgary, Alberta, T2N 4N1
University of Alberta
Edmonton, Alberta, T5G 2X8
Centre de Recherche du CHUM / University of Montreal
Montreal, Quebec, H2X 1P1
University of Toronto Western Hospital
Toronto, Ontario, M5T2S8
University of Manitoba
Winnipeg, Manitoba, R3E 3P4
United Kingdom5 sites
Queen Elizabeth Medical Center
Edgbaston, Birmingham, B15 2TH
Royal Infirmary
Edinburgh, EH16 4SA
Royal Free Hospital
Hampstead, London, NW3 2QG
John Radcliffe Hospital
Headington, Oxford, OX3 9DU
University Upon Tyne/Newcastle
Newcastle upon Tyne, NE2 4HH
Germany4 sites
Johann Wolfgang Goethe University
Frankfurt, 60590
University Medical Centre Hamburg-Eppendorf
Hamburg, D20246
Medical School of Hannover
Hanover, 30623
University of Munich
Munich, D81377
Netherlands2 sites
AMC University of Amsterdam
Amsterdam, NL-1100
Erasmus Medical Centre
Rotterdam, 3000
About this study
Official title: A Study of INT 747 (6α-ethyl Chenodeoxycholic Acid (6-ECDCA)) in Combination With Ursodeoxycholic Acid (URSO®, UDCA) in Patients With Primary Biliary Cirrhosis
The primary hypothesis is that INT-747 will cause a reduction in alkaline phosphatase levels in Primary Biliary Cirrhosis patients, over a 12 week treatment period, as compared to placebo.
Read the detailed description
None provided
- Conditions
- Liver Cirrhosis, Biliary
- Being tested
- INT-747, Ursodeoxycholic Acid (URSO), Placebo
- Keywords
- PBC, Primary Biliary Cirrhosis, Liver,
- 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.
INT-747Drug
Also called Obeticholic acid (OCA), 6-ECDCA
Once a day (QD) by mouth (PO)
Ursodeoxycholic Acid (URSO)Drug
Also called URSO, UDCA
Stable dose for at least 6 months prior to screening. Dose as prescribed by physician.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| INT-747 10 mg | Experimental | INT-747 10 mg once daily in combination with URSO for 12 weeks. Receives: Drug: INT-747; Drug: Ursodeoxycholic Acid (URSO) |
| INT-747 25 mg | Experimental | INT-747 25 mg once daily in combination with URSO for 12 weeks. Receives: Drug: INT-747; Drug: Ursodeoxycholic Acid (URSO) |
| INT-747 50 mg | Experimental | INT-747 50 mg once daily in combination with URSO for 12 weeks. Receives: Drug: INT-747; Drug: Ursodeoxycholic Acid (URSO) |
| Placebo | Placebo comparator | Placebo once daily in combination with URSO for 12 weeks. Receives: Drug: INT-747; Drug: Ursodeoxycholic Acid (URSO); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP)
Blood samples were collected for the analysis of serum ALP. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Measured: Baseline and Up to Day 85
Secondary outcomes (36)
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
Blood samples were collected for the analysis of serum chemistry parameters including ALP, AST, ALT and GGT. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and at Days 15, 29, 57 and 85
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
Blood samples were collected for the analysis of serum chemistry parameters including ALP, AST, ALT and GGT. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Measured: Baseline and at Days 15, 29, 57 and 85
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
Blood samples were collected for the analysis of serum chemistry parameters including ALP, AST, ALT and GGT. Baseline was defined as the last observed value before the first dose of investigational product (Day 85). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Measured: Baseline and at 3, 6, 9 and 12 Months
Double-blind Phase: Absolute Values for Albumin Levels
Blood samples were collected for the analysis of serum chemistry parameter: Albumin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and at Days 15, 29, 57 and 85
Double-blind Phase: Percent Change From Baseline in Albumin Levels
Blood samples were collected for the analysis of serum chemistry parameter: Albumin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Measured: Baseline and at Days 15, 29, 57 and 85
Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin
Blood samples were collected for the analysis of serum chemistry parameter: Conjugated (Direct) bilirubin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and at Days 15, 29, 57 and 85
Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin
Blood samples were collected for the analysis of serum chemistry parameter: Direct bilirubin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Measured: Baseline and at Days 15, 29, 57 and 85
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Blood samples were collected for the analysis of serum chemistry parameters Total and direct bilirubin. Baseline was defined as the last observed value before the first dose of investigational product (Day 85). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Measured: Baseline and at 3, 6, 9 and 12 Months
Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score
Enhanced Liver Fibrosis (ELF) combines measurements of tissue inhibitor of metalloprotein-ases-1 (TIMP-1), amino-terminal pro-peptide of type III procollagen (PIIINP), and hyaluronic acid (HA). The ELF score is calculated as: 2.278 + 0.851 ln (HA) + 0.751 ln (PIIINP) + 0.394 ln (TIMP-1). An ELF score of less than 7.7 indicates no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis. Higher the ELF is associated with higher fibrosis stages and greater the risk of progression. A minimum and maximum value for the scale range does not exist for this assessment. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and up to Day 85
Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels
Blood samples were collected for the analysis of extracellular matrix markers, including TIMP-1, PIIINP, and HA. The ELF score has been reported to show good correlations with fibrosis stages in chronic liver disease, with higher ELF scores associated with higher fibrosis stages. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including C-reactive protein. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including C-reactive protein. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA)
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including NEFA. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including NEFA. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha)
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including TNF-alpha. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including TNF-alpha. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta)
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including TNF-beta and TGF-beta. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including TNF-beta and TGF-beta. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including Bile acids and glutathion. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including Bile acids and glutathion. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM)
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including IgM. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including IgM. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including Osteopontin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin
Blood samples were collected for the analysis of biomarkers of hepatic inflammation including Osteopontin. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Total Endogenous Bile Acids
Serum samples were collected for the analysis total endogenous bile acids. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids
Serum samples were collected for the analysis of total endogenous bile acids. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline is defined as post-dose visit value minus Baseline value.
Measured: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19)
FGF-19 is a protein secreted by the gastro-intestine under farnesoid X receptor (FXR) control. Baseline was defined as the last observed value before the first dose of investigational product (Day 0).
Measured: Baseline and Up to Day 85
Double-blind Phase: Percent Change From Baseline Values for FGF19
FGF-19 is a protein secreted by the gastro-intestine under FXR control. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Measured: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. These eight dimensions can be summarized numerically into two scores: PCS and MCS; with score range from 0=worst to 100=best, with higher scores indicating better health. Increases from baseline indicate improvement. Baseline was defined as Day 0. Change from Baseline was defined as value of post Baseline minus Baseline value.
Measured: Baseline and Up to Day 85
LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. These eight dimensions can be summarized numerically into two scores: PCS and MCS; with score range from 0=worst to 100=best, with higher scores indicating better health. Increases from baseline indicate improvement. Baseline was defined as Day 85
Measured: Baseline and at 3, 6, 9 and 12 Months
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
PBC-40 is a disease-specific quality of life questionnaire,which consists of 5 Domains(score ranges):general symptoms (score range 7-35), itch (3-15), fatigue (11-55), cognitive function (6-30) and emotional (1-15); higher scores indicated worse outcomes.The 40 questions from the PBC-40 questionnaire were scored from 1 (lowest impact of PBC on QoL) to 5 (representing highest impact); Higher scores indicate worse quality of life. Outcomes of 'never', 'not at all' or 'strongly agree' are scored with 1, 'always', 'very much' or 'strongly disagree' with 5, with following exceptions: For questions 34-39 outcomes were scored in reverse,i.e., 'strongly agree' with 5, and 'strongly disagree' with 1. If less than 50% of the questions per domain were not answered, missing values were imputed by mean of the available question scores for that domain.If for any item multiple answers are given, most severe was used. Baseline = Day 0. Change from Baseline=post Baseline minus Baseline value.
Measured: Baseline and at Days 29, 57 and 85
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
PBC-40 is a disease-specific quality of life questionnaire, which consists of 5 Domains(score ranges):general symptoms (score range 7-35), itch (3-15), fatigue (11-55), cognitive function (6-30) and emotional (1-15); higher scores indicated worse outcomes.The 40 questions from the PBC-40 questionnaire were scored from 1 (lowest impact of PBC on QoL) to 5 (representing highest impact); Higher scores indicate worse quality of life. Outcomes of 'never', 'not at all' or 'strongly agree' are scored with 1, 'always', 'very much' or 'strongly disagree' with 5, with following exceptions: For questions 34-39 outcomes were scored in reverse,i.e., 'strongly agree' with 5, and 'strongly disagree' with 1. If less than 50% of the questions per domain were not answered, missing values were imputed by mean of the available question scores for that domain.If for any item multiple answers are given, most severe was used. Baseline = Day 85. Change from Baseline=post Baseline minus Baseline value.
Measured: Baseline and at 6 and 12 months
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
5-D questionnaire has 5 domains: Duration, degree, direction, disability, distribution, and total score. Single item domain scores (duration, degree, direction)=range:1-5.Disability domain has 4 items=assess impact of itching on daily activities: sleep, leisure/social activities, housework/errands, work/school;score calculated as highest score on any of 4 items; disability domain range=1-5.For distribution domain only section "Mark whether itching has been present in following parts of your body over the last 2 weeks" was used. Number of affected body parts('present') is tallied(potential sum 0-16);sum was sorted into 5 scoring bins: sum 0-2= score 1,sum 3-5=score 2,sum 6-10=score 3, sum 11-13=score 4,sum 14-16=score 5. Distribution score range reported=1-5. For all domains, higher scores=worse outcomes. Total 5D score=summing domain scores; ranges:5(no pruritus) to25 (most severe pruritus); Higher scores=worse outcomes. Baseline=Day 0.Change from Baseline=post Baseline minus Baseline
Measured: Baseline and at Days 29, 57 and 85
Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.
Measured: Up to Day 85
Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS)
A VAS questionnaire was used to assess participant's pruritus. The pruritus VAS measures participant's perception of itch on a continuous scale with score ranged from 0 = no itching and 10 = worst possible itching; higher score indicates worse outcomes. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Change from Baseline was defined as value of post Baseline minus Baseline value.
Measured: Baseline and at Days 29, 57 and 85
LTSE Phase: Number of Participants With TEAEs and SAEs
An AE was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.
Measured: Up to 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2007 (estimated)
- Study startOct 2007
- Primary completionAug 2009
- Study completionDec 2010
Why it stopped: Study stopped by sponsor due to administrative reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver Cirrhosis, BiliaryStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Intercept Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David A Shapiro, MD, Study director, Intercept Pharmaceuticals - Chief Medical Officer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00550862
- Sponsor's protocol ID
- 747-202
- Status last verified
- Jan 2024
- First submitted
- 27 Oct 2007
- Last updated
- 6 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hirschfield GM, Mason A, Luketic V, Lindor K, Gordon SC, Mayo M, Kowdley KV, Vincent C, Bodhenheimer HC Jr, Pares A, Trauner M, Marschall HU, Adorini L, Sciacca C, Beecher-Jones T, Castelloe E, Bohm O, Shapiro D. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology. 2015 Apr;148(4):751-61.e8. doi: 10.1053/j.gastro.2014.12.005. Epub 2014 Dec 11.
PubMed 25500425
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of INT 747 (6α-ethyl Chenodeoxycholic Acid (6-ECDCA)) in Combination With Ursodeoxycholic Acid (URSO®, UDCA) in Patients With Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT00550862
- Acronym / sponsor ID
- 747-202
- Conditions
- Liver Cirrhosis, Biliary
- Keywords
- PBC, Primary Biliary Cirrhosis, Liver,
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study stopped by sponsor due to administrative reasons
- Enrolment
- 165 participants (actual)
- Lead sponsor
- Intercept PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2007 (actual)
- Primary completion
- Aug 2009 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 30 Oct 2007 (estimated)
- Results
- Posted 23 Jan 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary hypothesis is that INT-747 will cause a reduction in alkaline phosphatase levels in Primary Biliary Cirrhosis patients, over a 12 week treatment period, as compared to placebo.
Detailed description
None provided
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| INT-747 10 mg | Experimental | Drug: INT-747, Drug: Ursodeoxycholic Acid (URSO)INT-747 10 mg once daily in combination with URSO for 12 weeks. |
| INT-747 25 mg | Experimental | Drug: INT-747, Drug: Ursodeoxycholic Acid (URSO)INT-747 25 mg once daily in combination with URSO for 12 weeks. |
| INT-747 50 mg | Experimental | Drug: INT-747, Drug: Ursodeoxycholic Acid (URSO)INT-747 50 mg once daily in combination with URSO for 12 weeks. |
| Placebo | Placebo comparator | Drug: INT-747, Drug: Ursodeoxycholic Acid (URSO), Drug: PlaceboPlacebo once daily in combination with URSO for 12 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female age 18 to 70 years.
- Stable dose of ursodeoxycholic acid (URSO, UDCA) for at least 6 months prior to screening.
- Female patients must be postmenopausal, surgically sterile, or prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of dosing.
- Male patients must be prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of the dosing.
- Proven or likely PBC, as demonstrated by the patient presenting with at least 2 of the following 3 diagnostic factors:
Key exclusion criteria (7 listed)
- Administration of the following drugs at any time during the 3 months prior to screening for the study: colchicine, methotrexate, azathioprine, or systemic corticosteroids.
- Screening conjugated (direct) bilirubin >2 × ULN.
- Screening ALT or AST >5 × ULN.
- Screening serum creatinine >1.5 mg/dL (133 mol/L).
- History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).
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 |
|---|---|---|
| INT-747Also: Obeticholic acid (OCA), 6-ECDCAOnce a day (QD) by mouth (PO) | Drug | INT-747 10 mg, INT-747 25 mg, INT-747 50 mg, Placebo |
| Ursodeoxycholic Acid (URSO)Also: URSO, UDCAStable dose for at least 6 months prior to screening. Dose as prescribed by physician. | Drug | INT-747 10 mg, INT-747 25 mg, INT-747 50 mg, Placebo |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP)
Time frame: Baseline and Up to Day 85
Blood samples were collected for the analysis of serum ALP. Baseline was defined as the last observed value before the first dose of investigational product (Day 0). Percent change from Baseline was calculated as Post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
36 secondary outcomes
Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels
Time frame: Baseline and at Days 15, 29, 57 and 85
Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
Time frame: Baseline and at Days 15, 29, 57 and 85
LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels
Time frame: Baseline and at 3, 6, 9 and 12 Months
Double-blind Phase: Absolute Values for Albumin Levels
Time frame: Baseline and at Days 15, 29, 57 and 85
Double-blind Phase: Percent Change From Baseline in Albumin Levels
Time frame: Baseline and at Days 15, 29, 57 and 85
Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin
Time frame: Baseline and at Days 15, 29, 57 and 85
Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin
Time frame: Baseline and at Days 15, 29, 57 and 85
LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin
Time frame: Baseline and at 3, 6, 9 and 12 Months
Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score
Time frame: Baseline and up to Day 85
Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels
Time frame: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein
Time frame: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein
Time frame: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA)
Time frame: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA
Time frame: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha)
Time frame: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha
Time frame: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta)
Time frame: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta
Time frame: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Time frame: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion
Time frame: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM)
Time frame: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM
Time frame: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin
Time frame: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin
Time frame: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Total Endogenous Bile Acids
Time frame: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids
Time frame: Baseline and Up to Day 85
Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19)
Time frame: Baseline and Up to Day 85
Double-blind Phase: Percent Change From Baseline Values for FGF19
Time frame: Baseline and Up to Day 85
Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale
Time frame: Baseline and Up to Day 85
LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale
Time frame: Baseline and at 3, 6, 9 and 12 Months
Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale
Time frame: Baseline and at Days 29, 57 and 85
LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale
Time frame: Baseline and at 6 and 12 months
Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale
Time frame: Baseline and at Days 29, 57 and 85
Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to Day 85
Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS)
Time frame: Baseline and at Days 29, 57 and 85
LTSE Phase: Number of Participants With TEAEs and SAEs
Time frame: Up to 12 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25500425Hirschfield GM, Mason A, Luketic V, Lindor K, Gordon SC, Mayo M, Kowdley KV, Vincent C, Bodhenheimer HC Jr, Pares A, Trauner M, Marschall HU, Adorini L, Sciacca C, Beecher-Jones T, Castelloe E, Bohm O, Shapiro D. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology. 2015 Apr;148(4):751-61.e8. doi: 10.1053/j.gastro.2014.12.005. Epub 2014 Dec 11.
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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.
David A Shapiro, MD study director
Intercept Pharmaceuticals - Chief Medical Officer
32 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing INT-747 and Ursodeoxycholic Acid (URSO) in people with Liver Cirrhosis, Biliary, run by Intercept Pharmaceuticals at 32 sites in 8 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 9 inclusion and 7 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 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Canada, United Kingdom, Germany, Netherlands and 3 more countries. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP) (time frame: Baseline and Up to Day 85). 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 NCT00550862, which also lists 1 linked publication.
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 6 Feb 2024.