Liver Cirrhosis, Biliary
Conditions
Keywords
PBC, Primary Biliary Cirrhosis, Liver,
Brief 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.
Detailed description
None provided
Interventions
DRUGINT-747
Once a day (QD) by mouth (PO)
Stable dose for at least 6 months prior to screening. Dose as prescribed by physician.
DRUGPlacebo
Placebo
Sponsors
Intercept Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 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: 1. History of increased AP levels for at least 6 months prior to Day 0 2. Positive AMA titer (\>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive) 3. Liver biopsy consistent with PBC. * Screening AP value between 1.5 and 10 × ULN.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | Baseline and at Days 15, 29, 57 and 85 | 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. |
| LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | Baseline and at 3, 6, 9 and 12 Months | 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. |
| Double-blind Phase: Absolute Values for Albumin Levels | Baseline and at Days 15, 29, 57 and 85 | 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). |
| Double-blind Phase: Percent Change From Baseline in Albumin Levels | Baseline and at Days 15, 29, 57 and 85 | 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. |
| Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Baseline and at Days 15, 29, 57 and 85 | 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). |
| Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Baseline and at Days 15, 29, 57 and 85 | 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. |
| LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin | Baseline and at 3, 6, 9 and 12 Months | 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. |
| Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score | Baseline and up to Day 85 | 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. |
| Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Baseline and Up to Day 85 | 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). |
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA) | Baseline and Up to Day 85 | 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). |
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha) | Baseline and Up to Day 85 | 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). |
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | Baseline and Up to Day 85 | 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). |
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | Baseline and at Days 15, 29, 57 and 85 | 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). |
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM) | Baseline and Up to Day 85 | 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). |
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin | Baseline and Up to Day 85 | 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). |
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Absolute Values for Total Endogenous Bile Acids | Baseline and Up to Day 85 | 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). |
| Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19) | Baseline and Up to Day 85 | 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). |
| Double-blind Phase: Percent Change From Baseline Values for FGF19 | Baseline and Up to Day 85 | 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. |
| Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale | Baseline and Up to Day 85 | 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. |
| LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale | Baseline and at 3, 6, 9 and 12 Months | 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 |
| Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Baseline and at Days 29, 57 and 85 | 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. |
| LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | Baseline and at 6 and 12 months | 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. |
| Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Baseline and at Days 29, 57 and 85 | 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 |
| Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to Day 85 | 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. |
| Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Baseline and at Days 29, 57 and 85 | 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. |
| LTSE Phase: Number of Participants With TEAEs and SAEs | Up to 12 Months | 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. |
| Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Baseline and Up to Day 85 | 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). |
Countries
Austria, Canada, France, Germany, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was an international, multi-center, randomized, double-blind, placebo-controlled, multi-dose study with the majority of the sites being academic centers.
Pre-assignment details
A total of 165 participants were enrolled into the double-blind phase of the study. Of these, 78 participants (21 of whom had received placebo) entered the open-label long-term safety extension (LTSE) phase
Participants by arm
| Arm | Count |
|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) Participants were randomized to receive OCA 10 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until end of study (EOS) (Day 85). | 38 |
| OCA 25 mg Participants were randomized to receive OCA 25 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85). | 48 |
| OCA 50 mg Participants were randomized to receive OCA 50 mg orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85). | 41 |
| Placebo Participants were randomized to receive placebo orally as a capsule once daily from Day 1 to Day 85 approximately 30 minutes before breakfast with water. Participants were instructed to swallow the capsule whole and not to chew, divide, or crush the capsule. Per the titration strategy, the participants were administered investigational product once every 3 days in the first week, once every 2 days in the second week, and daily from the third week onwards until EOS (Day 85). | 38 |
| Total | 165 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Double-Blind Phase (Day 1 to Day 85) | Adverse Event | 5 | 5 | 12 | 1 | 0 |
| Double-Blind Phase (Day 1 to Day 85) | Elevated aspartate transaminase (AST)/ alanine transaminase (ALT) levels | 0 | 0 | 1 | 0 | 0 |
| Double-Blind Phase (Day 1 to Day 85) | Elevated conjugated (direct) bilirubin | 1 | 0 | 2 | 0 | 0 |
| Double-Blind Phase (Day 1 to Day 85) | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Double-Blind Phase (Day 1 to Day 85) | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
| LTSE Phase (Up to 12 Months) | Adverse Event | 0 | 0 | 0 | 0 | 14 |
| LTSE Phase (Up to 12 Months) | Other | 0 | 0 | 0 | 0 | 2 |
| LTSE Phase (Up to 12 Months) | Other: Study stopped by sponsor due to administrative reasons | 0 | 0 | 0 | 0 | 59 |
| LTSE Phase (Up to 12 Months) | Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| LTSE Phase (Up to 12 Months) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 50 mg | OCA 25 mg |
|---|---|---|---|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 8.8 | 54.8 years STANDARD_DEVIATION 8.5 | 55.6 years STANDARD_DEVIATION 9.3 | 54.0 years STANDARD_DEVIATION 9.7 | 55.9 years STANDARD_DEVIATION 8 |
| Race/Ethnicity, Customized Asian | 2 participants | 1 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black | 2 participants | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Other | 3 participants | 2 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 158 participants | 34 participants | 37 participants | 40 participants | 47 participants |
| Region of Enrollment Austria | 6 participants | 1 participants | 1 participants | 2 participants | 2 participants |
| Region of Enrollment Canada | 55 participants | 13 participants | 13 participants | 14 participants | 15 participants |
| Region of Enrollment France | 2 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Germany | 8 participants | 1 participants | 2 participants | 2 participants | 3 participants |
| Region of Enrollment Netherlands | 4 participants | 1 participants | 1 participants | 1 participants | 1 participants |
| Region of Enrollment Spain | 6 participants | 2 participants | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United Kingdom | 12 participants | 3 participants | 4 participants | 2 participants | 3 participants |
| Region of Enrollment United States | 72 participants | 17 participants | 15 participants | 19 participants | 21 participants |
| Sex: Female, Male Female | 157 Participants | 36 Participants | 38 Participants | 38 Participants | 45 Participants |
| Sex: Female, Male Male | 8 Participants | 2 Participants | 0 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 48 | 0 / 41 | 0 / 38 | 0 / 78 |
| other Total, other adverse events | 34 / 38 | 47 / 48 | 41 / 41 | 32 / 38 | 76 / 78 |
| serious Total, serious adverse events | 0 / 38 | 1 / 48 | 5 / 41 | 1 / 38 | 5 / 78 |
Outcome results
Primary
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.
Time frame: Baseline and Up to Day 85
Population: Modified Intent-to-Treat (mITT) Population (N=161) comprised of all randomized participants who received at least 1 dose of investigational product and had at least 1 post-Baseline ALP evaluation taken ≤7 days after their last dose of investigational product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP) | -23.7 Percent change | Standard Deviation 17.8 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP) | -24.7 Percent change | Standard Deviation 17.9 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP) | -21.0 Percent change | Standard Deviation 27.6 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP) | -2.6 Percent change | Standard Deviation 12.5 |
Comparison: All tests: Descriptive methods were used with nominal p values provided and 95% confidence intervals.p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: All tests: Descriptive methods were used with nominal p values provided and 95% confidence intervals.p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: All tests: Descriptive methods were used with nominal p values provided and 95% confidence intervalsp-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
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).
Time frame: Baseline and at Days 15, 29, 57 and 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Albumin Levels | Day 57 | 40.29 Grams per liter | Standard Deviation 3.65 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Albumin Levels | Day 15 | 39.84 Grams per liter | Standard Deviation 4.33 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Albumin Levels | Day 85 | 39.95 Grams per liter | Standard Deviation 4.19 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Albumin Levels | Day 29 | 40.01 Grams per liter | Standard Deviation 3.38 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Albumin Levels | Baseline | 40.14 Grams per liter | Standard Deviation 4.66 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Albumin Levels | Day 29 | 40.94 Grams per liter | Standard Deviation 3.74 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Albumin Levels | Day 57 | 41.04 Grams per liter | Standard Deviation 3.9 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Albumin Levels | Day 85 | 41.09 Grams per liter | Standard Deviation 4.01 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Albumin Levels | Day 15 | 41.12 Grams per liter | Standard Deviation 3.59 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Albumin Levels | Baseline | 41.17 Grams per liter | Standard Deviation 3.85 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Albumin Levels | Day 29 | 41.05 Grams per liter | Standard Deviation 3.64 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Albumin Levels | Baseline | 42.41 Grams per liter | Standard Deviation 2.77 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Albumin Levels | Day 15 | 41.15 Grams per liter | Standard Deviation 3.05 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Albumin Levels | Day 57 | 41.76 Grams per liter | Standard Deviation 3 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Albumin Levels | Day 85 | 41.24 Grams per liter | Standard Deviation 3.86 |
| Placebo | Double-blind Phase: Absolute Values for Albumin Levels | Day 57 | 40.50 Grams per liter | Standard Deviation 4.33 |
| Placebo | Double-blind Phase: Absolute Values for Albumin Levels | Day 15 | 41.84 Grams per liter | Standard Deviation 3.38 |
| Placebo | Double-blind Phase: Absolute Values for Albumin Levels | Baseline | 42.03 Grams per liter | Standard Deviation 3.23 |
| Placebo | Double-blind Phase: Absolute Values for Albumin Levels | Day 29 | 41.21 Grams per liter | Standard Deviation 3.5 |
| Placebo | Double-blind Phase: Absolute Values for Albumin Levels | Day 85 | 41.69 Grams per liter | Standard Deviation 4.05 |
Secondary
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).
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=144).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids, Day 85 | 37.8 Micromoles per liter | Standard Deviation 47.3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione, Day 85 | 5.0 Micromoles per liter | Standard Deviation 2.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids, Baseline | 36.9 Micromoles per liter | Standard Deviation 31.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione, Baseline | 3.7 Micromoles per liter | Standard Deviation 1.3 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids, Baseline | 29.5 Micromoles per liter | Standard Deviation 26.1 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione, Day 85 | 5.3 Micromoles per liter | Standard Deviation 1.9 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids, Day 85 | 30.2 Micromoles per liter | Standard Deviation 42.9 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione, Baseline | 4.0 Micromoles per liter | Standard Deviation 1.9 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids, Baseline | 36.0 Micromoles per liter | Standard Deviation 48.9 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione, Day 85 | 4.8 Micromoles per liter | Standard Deviation 2 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione, Baseline | 3.4 Micromoles per liter | Standard Deviation 1.6 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids, Day 85 | 34.6 Micromoles per liter | Standard Deviation 57.2 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione, Day 85 | 4.8 Micromoles per liter | Standard Deviation 1.9 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids, Day 85 | 26.2 Micromoles per liter | Standard Deviation 29.2 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione, Baseline | 3.8 Micromoles per liter | Standard Deviation 1.8 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids, Baseline | 27.6 Micromoles per liter | Standard Deviation 32.3 |
Secondary
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).
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n-144).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Baseline | 7.9 Milligrams per milliliter | Standard Deviation 7.5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Day 85 | 6.4 Milligrams per milliliter | Standard Deviation 7.2 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Day 85 | 4.0 Milligrams per milliliter | Standard Deviation 4.4 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Baseline | 7.8 Milligrams per milliliter | Standard Deviation 8.9 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Baseline | 5.2 Milligrams per milliliter | Standard Deviation 5.6 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Day 85 | 6.0 Milligrams per milliliter | Standard Deviation 13.2 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Baseline | 5.1 Milligrams per milliliter | Standard Deviation 4.6 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | Day 85 | 6.0 Milligrams per milliliter | Standard Deviation 5.8 |
Secondary
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).
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=144).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM) | Baseline | 4.31 Grams per liter | Standard Deviation 2.12 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM) | Day 85 | 3.73 Grams per liter | Standard Deviation 1.91 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM) | Day 85 | 2.62 Grams per liter | Standard Deviation 1.76 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM) | Baseline | 3.13 Grams per liter | Standard Deviation 1.95 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM) | Baseline | 3.82 Grams per liter | Standard Deviation 3.35 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM) | Day 85 | 3.02 Grams per liter | Standard Deviation 2.14 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM) | Baseline | 3.06 Grams per liter | Standard Deviation 1.73 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Immunoglobulin M (IgM) | Day 85 | 2.97 Grams per liter | Standard Deviation 1.61 |
Secondary
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).
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=143).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA) | Baseline | 0.58 Millimoles per liter | Standard Deviation 0.23 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA) | Day 85 | 0.49 Millimoles per liter | Standard Deviation 0.24 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA) | Day 85 | 0.51 Millimoles per liter | Standard Deviation 0.19 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA) | Baseline | 0.55 Millimoles per liter | Standard Deviation 0.24 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA) | Baseline | 0.62 Millimoles per liter | Standard Deviation 0.23 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA) | Day 85 | 0.55 Millimoles per liter | Standard Deviation 0.25 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA) | Baseline | 0.54 Millimoles per liter | Standard Deviation 0.26 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Non-essential Fatty Acid (NEFA) | Day 85 | 0.56 Millimoles per liter | Standard Deviation 0.19 |
Secondary
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).
Time frame: Baseline and Up to Day 85
Population: ITT Population (165). Only those participants with data available at specified timepoints has been presented (n=144).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin | Baseline | 305 Micrograms per liter | Standard Deviation 175 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin | Day 85 | 335 Micrograms per liter | Standard Deviation 187 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin | Day 85 | 318 Micrograms per liter | Standard Deviation 131 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin | Baseline | 279 Micrograms per liter | Standard Deviation 118 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin | Baseline | 286 Micrograms per liter | Standard Deviation 122 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin | Day 85 | 350 Micrograms per liter | Standard Deviation 170 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin | Baseline | 264 Micrograms per liter | Standard Deviation 130 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Osteopontin | Day 85 | 245 Micrograms per liter | Standard Deviation 115 |
Secondary
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).
Time frame: Baseline and Up to Day 85
Population: ITT Population (N-165). Only those participants with data available at specified timepoints has been presented (142).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TNF-beta, Baseline | 13.1 Picomoles per liter | Standard Deviation 14.8 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TNF-beta, Day 85 | 11.0 Picomoles per liter | Standard Deviation 7.8 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TGF-beta, Baseline | 35.6 Picomoles per liter | Standard Deviation 22 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TGF-beta, Day 85 | 39.2 Picomoles per liter | Standard Deviation 22.9 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TNF-beta, Day 85 | 14.5 Picomoles per liter | Standard Deviation 17 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TGF-beta, Baseline | 37.0 Picomoles per liter | Standard Deviation 23.3 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TGF-beta, Day 85 | 41.0 Picomoles per liter | Standard Deviation 25.7 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TNF-beta, Baseline | 10.8 Picomoles per liter | Standard Deviation 12.2 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TGF-beta, Baseline | 26.2 Picomoles per liter | Standard Deviation 22.9 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TNF-beta, Day 85 | 6.7 Picomoles per liter | Standard Deviation 7.6 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TGF-beta, Day 85 | 40.4 Picomoles per liter | Standard Deviation 22.3 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TNF-beta, Baseline | 8.7 Picomoles per liter | Standard Deviation 10.4 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TGF-beta, Day 85 | 30.1 Picomoles per liter | Standard Deviation 23.1 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TNF-beta, Day 85 | 10.9 Picomoles per liter | Standard Deviation 17.3 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TNF-beta, Baseline | 8.8 Picomoles per liter | Standard Deviation 12 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: TNF-beta and Tumor Growth Factor Beta (TGF-beta) | TGF-beta, Baseline | 36.4 Picomoles per liter | Standard Deviation 25.3 |
Secondary
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).
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=144).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha) | Baseline | 15.6 Nanograms per liter | Standard Deviation 7.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha) | Day 85 | 18.1 Nanograms per liter | Standard Deviation 14.8 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha) | Day 85 | 15.4 Nanograms per liter | Standard Deviation 7.3 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha) | Baseline | 13.8 Nanograms per liter | Standard Deviation 4.4 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha) | Baseline | 16.1 Nanograms per liter | Standard Deviation 11.7 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha) | Day 85 | 16.2 Nanograms per liter | Standard Deviation 12.1 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha) | Baseline | 11.4 Nanograms per liter | Standard Deviation 3.2 |
| Placebo | Double-blind Phase: Absolute Values for Biomarkers of Hepatic Inflammation: Tumor Necrosis Factor Alpha (TNF-alpha) | Day 85 | 13.6 Nanograms per liter | Standard Deviation 4.5 |
Secondary
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).
Time frame: Baseline and at Days 15, 29, 57 and 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 57 | 3.4 Micromoles per liter | Standard Deviation 3.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 15 | 4.9 Micromoles per liter | Standard Deviation 5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 85 | 3.9 Micromoles per liter | Standard Deviation 3.8 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 29 | 3.3 Micromoles per liter | Standard Deviation 2.6 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Baseline | 4.2 Micromoles per liter | Standard Deviation 3.1 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 29 | 3.3 Micromoles per liter | Standard Deviation 2.6 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 57 | 3.4 Micromoles per liter | Standard Deviation 2.6 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 85 | 3.2 Micromoles per liter | Standard Deviation 2.7 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 15 | 3.1 Micromoles per liter | Standard Deviation 2.2 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Baseline | 3.9 Micromoles per liter | Standard Deviation 2.4 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 29 | 5.6 Micromoles per liter | Standard Deviation 14.4 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Baseline | 4.7 Micromoles per liter | Standard Deviation 3.3 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 15 | 3.3 Micromoles per liter | Standard Deviation 2.2 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 57 | 3.0 Micromoles per liter | Standard Deviation 1.6 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 85 | 5.5 Micromoles per liter | Standard Deviation 8.5 |
| Placebo | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 57 | 3.5 Micromoles per liter | Standard Deviation 3 |
| Placebo | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 15 | 3.4 Micromoles per liter | Standard Deviation 2.4 |
| Placebo | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Baseline | 3.6 Micromoles per liter | Standard Deviation 2.8 |
| Placebo | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 29 | 3.7 Micromoles per liter | Standard Deviation 2.8 |
| Placebo | Double-blind Phase: Absolute Values for Conjugated (Direct) Bilirubin | Day 85 | 3.6 Micromoles per liter | Standard Deviation 3.2 |
Secondary
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).
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=143).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19) | Baseline | 102.9 Nanograms per liter | Standard Deviation 60.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19) | Day 85 | 248.2 Nanograms per liter | Standard Deviation 221.3 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19) | Day 85 | 386.9 Nanograms per liter | Standard Deviation 443.9 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19) | Baseline | 104.1 Nanograms per liter | Standard Deviation 64.5 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19) | Baseline | 115.7 Nanograms per liter | Standard Deviation 122.4 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19) | Day 85 | 2269.7 Nanograms per liter | Standard Deviation 9874.8 |
| Placebo | Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19) | Baseline | 84.1 Nanograms per liter | Standard Deviation 56.1 |
| Placebo | Double-blind Phase: Absolute Values for Fibroblast Growth Factor 19 (FGF19) | Day 85 | 95.6 Nanograms per liter | Standard Deviation 65.6 |
Secondary
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).
Time frame: Baseline and at Days 15, 29, 57 and 85
Population: Intent-to-Treat (ITT) Population (N=165) comprises all randomized participants who received at least 1 dose of investigational product. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Baseline | 228 Units per liter | Standard Deviation 212 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 15 | 40 Units per liter | Standard Deviation 20 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 57 | 212.6 Units per liter | Standard Deviation 98.9 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 85 | 34 Units per liter | Standard Deviation 20 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 29 | 35 Units per liter | Standard Deviation 15 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Baseline | 294.4 Units per liter | Standard Deviation 149.4 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 57 | 32 Units per liter | Standard Deviation 16 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 15 | 247.6 Units per liter | Standard Deviation 117.9 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 57 | 96 Units per liter | Standard Deviation 91 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 85 | 219.0 Units per liter | Standard Deviation 113.5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Baseline | 49 Units per liter | Standard Deviation 22 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 29 | 108 Units per liter | Standard Deviation 92 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 15 | 44 Units per liter | Standard Deviation 23 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 85 | 107 Units per liter | Standard Deviation 124 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 29 | 37 Units per liter | Standard Deviation 13 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 29 | 227.2 Units per liter | Standard Deviation 105 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 15 | 137 Units per liter | Standard Deviation 119 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 57 | 36 Units per liter | Standard Deviation 14 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 85 | 40 Units per liter | Standard Deviation 23 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Baseline | 51 Units per liter | Standard Deviation 29 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Baseline | 273 Units per liter | Standard Deviation 267 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Baseline | 51 Units per liter | Standard Deviation 36 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 57 | 104 Units per liter | Standard Deviation 189 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 85 | 34 Units per liter | Standard Deviation 38 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Baseline | 44 Units per liter | Standard Deviation 23 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 15 | 37 Units per liter | Standard Deviation 28 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Baseline | 290.0 Units per liter | Standard Deviation 123.6 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 85 | 115 Units per liter | Standard Deviation 178 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 85 | 37 Units per liter | Standard Deviation 25 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 29 | 32 Units per liter | Standard Deviation 25 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 15 | 38 Units per liter | Standard Deviation 19 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 57 | 39 Units per liter | Standard Deviation 70 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 57 | 40 Units per liter | Standard Deviation 45 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 57 | 231.7 Units per liter | Standard Deviation 177.6 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 15 | 155 Units per liter | Standard Deviation 197 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 29 | 219.2 Units per liter | Standard Deviation 100.5 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 29 | 36 Units per liter | Standard Deviation 19 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 85 | 225.0 Units per liter | Standard Deviation 169.1 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 15 | 239.3 Units per liter | Standard Deviation 113.6 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 29 | 109 Units per liter | Standard Deviation 153 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 29 | 43 Units per liter | Standard Deviation 40 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Baseline | 289.5 Units per liter | Standard Deviation 106.2 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 15 | 231.2 Units per liter | Standard Deviation 87.5 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 29 | 216.1 Units per liter | Standard Deviation 90.5 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 57 | 189.2 Units per liter | Standard Deviation 67.5 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 85 | 227.9 Units per liter | Standard Deviation 115.9 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Baseline | 48 Units per liter | Standard Deviation 24 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 15 | 47 Units per liter | Standard Deviation 34 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 29 | 43 Units per liter | Standard Deviation 28 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 57 | 37 Units per liter | Standard Deviation 17 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 85 | 41 Units per liter | Standard Deviation 24 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Baseline | 53 Units per liter | Standard Deviation 35 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 15 | 49 Units per liter | Standard Deviation 49 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 57 | 34 Units per liter | Standard Deviation 23 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 85 | 39 Units per liter | Standard Deviation 32 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Baseline | 231 Units per liter | Standard Deviation 182 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 15 | 108 Units per liter | Standard Deviation 88 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 29 | 93 Units per liter | Standard Deviation 90 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 57 | 76 Units per liter | Standard Deviation 86 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 85 | 95 Units per liter | Standard Deviation 89 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 85 | 41 Units per liter | Standard Deviation 17 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 57 | 45 Units per liter | Standard Deviation 28 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 57 | 195 Units per liter | Standard Deviation 165 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Baseline | 189 Units per liter | Standard Deviation 139 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 29 | 42 Units per liter | Standard Deviation 20 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Day 15 | 41 Units per liter | Standard Deviation 17 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 15 | 269.2 Units per liter | Standard Deviation 105.6 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 15 | 190 Units per liter | Standard Deviation 141 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | AST, Baseline | 42 Units per liter | Standard Deviation 19 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 85 | 270.7 Units per liter | Standard Deviation 118.7 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Baseline | 275.2 Units per liter | Standard Deviation 102.7 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 29 | 196 Units per liter | Standard Deviation 158 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 57 | 271.5 Units per liter | Standard Deviation 123 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 29 | 46 Units per liter | Standard Deviation 25 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALP, Day 29 | 266.1 Units per liter | Standard Deviation 118 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 57 | 49 Units per liter | Standard Deviation 29 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 15 | 48 Units per liter | Standard Deviation 24 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Baseline | 47 Units per liter | Standard Deviation 26 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | GGT, Day 85 | 209 Units per liter | Standard Deviation 170 |
| Placebo | Double-blind Phase: Absolute Values for Serum ALP, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT) and Gamma-glutamyl Transferase (GGT) Levels | ALT, Day 85 | 45 Units per liter | Standard Deviation 24 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
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).
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=143).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Total Endogenous Bile Acids | Baseline | 11.011 Micromoles per liter | Standard Deviation 9.071 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Absolute Values for Total Endogenous Bile Acids | Day 85 | 9.516 Micromoles per liter | Standard Deviation 14.945 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Total Endogenous Bile Acids | Day 85 | 5.948 Micromoles per liter | Standard Deviation 15.59 |
| OCA 25 mg | Double-blind Phase: Absolute Values for Total Endogenous Bile Acids | Baseline | 10.013 Micromoles per liter | Standard Deviation 12.86 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Total Endogenous Bile Acids | Baseline | 16.048 Micromoles per liter | Standard Deviation 28.325 |
| OCA 50 mg | Double-blind Phase: Absolute Values for Total Endogenous Bile Acids | Day 85 | 23.935 Micromoles per liter | Standard Deviation 54.351 |
| Placebo | Double-blind Phase: Absolute Values for Total Endogenous Bile Acids | Baseline | 6.350 Micromoles per liter | Standard Deviation 9.524 |
| Placebo | Double-blind Phase: Absolute Values for Total Endogenous Bile Acids | Day 85 | 8.796 Micromoles per liter | Standard Deviation 11.557 |
Secondary
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.
Time frame: Baseline and up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=146).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score | -0.095 Scores on a scale | Standard Deviation 0.593 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score | 0.008 Scores on a scale | Standard Deviation 0.561 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score | 0.124 Scores on a scale | Standard Deviation 0.685 |
| Placebo | Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score | -0.212 Scores on a scale | Standard Deviation 0.627 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=146).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | HA | -6.771 Nanograms per milliliter | Standard Deviation 59.677 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | TIMP-1 | 15.341 Nanograms per milliliter | Standard Deviation 218.71 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | P3NP | -0.503 Nanograms per milliliter | Standard Deviation 3.017 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | HA | 12.287 Nanograms per milliliter | Standard Deviation 73.09 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | TIMP-1 | -18.409 Nanograms per milliliter | Standard Deviation 191.768 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | P3NP | -0.468 Nanograms per milliliter | Standard Deviation 2.389 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | P3NP | 1.858 Nanograms per milliliter | Standard Deviation 6.547 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | HA | 20.117 Nanograms per milliliter | Standard Deviation 97.056 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | TIMP-1 | 43.921 Nanograms per milliliter | Standard Deviation 222.93 |
| Placebo | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | HA | -21.359 Nanograms per milliliter | Standard Deviation 69.389 |
| Placebo | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | TIMP-1 | -65.196 Nanograms per milliliter | Standard Deviation 257.295 |
| Placebo | Double-blind Phase: Change From Baseline in HA, P3NP, and TIMP-1 Levels | P3NP | -0.943 Nanograms per milliliter | Standard Deviation 3.206 |
Secondary
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.
Time frame: Baseline and at Days 29, 57 and 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=152).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 29 | 11.5 Scores on a scale | Standard Deviation 19.5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 85 | 6.5 Scores on a scale | Standard Deviation 22.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 57 | 7.0 Scores on a scale | Standard Deviation 25.7 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 29 | 17.8 Scores on a scale | Standard Deviation 26.3 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 85 | 12.9 Scores on a scale | Standard Deviation 24.5 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 57 | 15.4 Scores on a scale | Standard Deviation 24.7 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 57 | 13.7 Scores on a scale | Standard Deviation 25.7 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 29 | 22.8 Scores on a scale | Standard Deviation 33.2 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 85 | 17.2 Scores on a scale | Standard Deviation 28.9 |
| Placebo | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 29 | -2.6 Scores on a scale | Standard Deviation 16.3 |
| Placebo | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 85 | -5.8 Scores on a scale | Standard Deviation 20.5 |
| Placebo | Double-blind Phase: Change From Baseline in Pruritus Visual Analog Scale (VAS) | Day 57 | -10.7 Scores on a scale | Standard Deviation 19.6 |
Secondary
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
Time frame: Baseline and at Days 29, 57 and 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=163).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 29 | 0.5 Scores on a scale | Standard Deviation 1.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 85 | 0.4 Scores on a scale | Standard Deviation 0.9 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 85 | 0.2 Scores on a scale | Standard Deviation 0.8 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 85 | 0.6 Scores on a scale | Standard Deviation 0.9 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 57 | 0.3 Scores on a scale | Standard Deviation 1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 29 | 0.5 Scores on a scale | Standard Deviation 0.8 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 29 | 0.6 Scores on a scale | Standard Deviation 0.9 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 85 | 0.3 Scores on a scale | Standard Deviation 1.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 85 | 1.3 Scores on a scale | Standard Deviation 3.8 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 29 | 2.6 Scores on a scale | Standard Deviation 3.4 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 57 | 0.4 Scores on a scale | Standard Deviation 1.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 29 | 0.7 Scores on a scale | Standard Deviation 1.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 29 | 0.3 Scores on a scale | Standard Deviation 0.9 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 57 | 0.5 Scores on a scale | Standard Deviation 1.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 85 | -0.2 Scores on a scale | Standard Deviation 1.5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 57 | 0.0 Scores on a scale | Standard Deviation 1.3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 57 | 0.4 Scores on a scale | Standard Deviation 1.3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 57 | 1.8 Scores on a scale | Standard Deviation 4.5 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 85 | 1.7 Scores on a scale | Standard Deviation 4 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 29 | 3.0 Scores on a scale | Standard Deviation 4.7 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 57 | 2.6 Scores on a scale | Standard Deviation 3.9 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 29 | 0.7 Scores on a scale | Standard Deviation 1.5 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 57 | 0.6 Scores on a scale | Standard Deviation 1.1 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 85 | 0.4 Scores on a scale | Standard Deviation 1.1 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 29 | 0.6 Scores on a scale | Standard Deviation 1 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 57 | 0.7 Scores on a scale | Standard Deviation 1 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 85 | 0.6 Scores on a scale | Standard Deviation 1 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 29 | 0.2 Scores on a scale | Standard Deviation 1.5 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 57 | 0.1 Scores on a scale | Standard Deviation 1.5 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 85 | -0.2 Scores on a scale | Standard Deviation 1.5 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 29 | 0.7 Scores on a scale | Standard Deviation 1.2 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 57 | 0.6 Scores on a scale | Standard Deviation 1.1 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 85 | 0.6 Scores on a scale | Standard Deviation 1.2 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 29 | 0.8 Scores on a scale | Standard Deviation 1.5 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 57 | 0.8 Scores on a scale | Standard Deviation 1.2 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 85 | 0.8 Scores on a scale | Standard Deviation 1.2 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 57 | 0.5 Scores on a scale | Standard Deviation 1 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 29 | -0.2 Scores on a scale | Standard Deviation 1.6 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 57 | -0.2 Scores on a scale | Standard Deviation 1.4 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 29 | 1.2 Scores on a scale | Standard Deviation 1.6 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 85 | 1.2 Scores on a scale | Standard Deviation 1.5 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 85 | 0.1 Scores on a scale | Standard Deviation 1.4 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 57 | 1.4 Scores on a scale | Standard Deviation 1.3 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 29 | 1.3 Scores on a scale | Standard Deviation 1.5 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 85 | 4.2 Scores on a scale | Standard Deviation 5.1 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 57 | 0.8 Scores on a scale | Standard Deviation 1.2 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 29 | 4.4 Scores on a scale | Standard Deviation 5.4 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 85 | 1.0 Scores on a scale | Standard Deviation 1.4 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 57 | 2.9 Scores on a scale | Standard Deviation 3.3 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 29 | 1.0 Scores on a scale | Standard Deviation 1.1 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 85 | 0.8 Scores on a scale | Standard Deviation 1.2 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 57 | 0.7 Scores on a scale | Standard Deviation 1 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 29 | 1.4 Scores on a scale | Standard Deviation 1.6 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 85 | 0.9 Scores on a scale | Standard Deviation 1.1 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 29 | 0.0 Scores on a scale | Standard Deviation 0.6 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 29 | -0.2 Scores on a scale | Standard Deviation 0.9 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 57 | -0.4 Scores on a scale | Standard Deviation 1.1 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 29 | -0.3 Scores on a scale | Standard Deviation 1.2 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 29 | 0.1 Scores on a scale | Standard Deviation 1 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 29 | -0.7 Scores on a scale | Standard Deviation 2.9 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 57 | -1.8 Scores on a scale | Standard Deviation 3 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 57 | -0.7 Scores on a scale | Standard Deviation 1.4 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 57 | -0.3 Scores on a scale | Standard Deviation 0.7 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 85 | -0.2 Scores on a scale | Standard Deviation 1 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 85 | -0.4 Scores on a scale | Standard Deviation 1.2 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Direction, Day 85 | -0.5 Scores on a scale | Standard Deviation 1.5 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Total score, Day 85 | -1.5 Scores on a scale | Standard Deviation 3.8 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Duration, Day 85 | -0.2 Scores on a scale | Standard Deviation 0.8 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 85 | -0.2 Scores on a scale | Standard Deviation 0.7 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Disability, Day 29 | -0.3 Scores on a scale | Standard Deviation 0.9 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Degree, Day 57 | -0.2 Scores on a scale | Standard Deviation 0.8 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life as Determined by 5-Dimension (5-D) Domain Scale | Distribution, Day 57 | -0.2 Scores on a scale | Standard Deviation 0.8 |
Secondary
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.
Time frame: Baseline and at Days 29, 57 and 85
Population: Safety Population. Only those participants with data available at specified time points has been presented (n=163).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 29 | -0.4 Scores on a scale | Standard Deviation 2.4 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 85 | -0.2 Scores on a scale | Standard Deviation 2.5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 85 | -0.4 Scores on a scale | Standard Deviation 4.3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 85 | 0.3 Scores on a scale | Standard Deviation 2.9 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 29 | -0.1 Scores on a scale | Standard Deviation 2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 57 | -0.3 Scores on a scale | Standard Deviation 2.8 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 29 | 0.6 Scores on a scale | Standard Deviation 2.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 57 | 0.1 Scores on a scale | Standard Deviation 2.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 57 | 0.7 Scores on a scale | Standard Deviation 5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 57 | 0.6 Scores on a scale | Standard Deviation 2.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 85 | 1.1 Scores on a scale | Standard Deviation 2.6 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 29 | 0.7 Scores on a scale | Standard Deviation 4.4 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 29 | -0.5 Scores on a scale | Standard Deviation 4.6 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 85 | 0.5 Scores on a scale | Standard Deviation 4.6 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 57 | -0.3 Scores on a scale | Standard Deviation 4.7 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 57 | -0.6 Scores on a scale | Standard Deviation 5 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 85 | 0.0 Scores on a scale | Standard Deviation 3.1 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 57 | 2.0 Scores on a scale | Standard Deviation 3 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 85 | 0.4 Scores on a scale | Standard Deviation 4.6 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 57 | -0.5 Scores on a scale | Standard Deviation 2.2 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 57 | -0.2 Scores on a scale | Standard Deviation 2.8 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 29 | -1.1 Scores on a scale | Standard Deviation 3.6 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 29 | -0.5 Scores on a scale | Standard Deviation 2 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 85 | 0.0 Scores on a scale | Standard Deviation 2.8 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 29 | -1.3 Scores on a scale | Standard Deviation 5.1 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 85 | -0.6 Scores on a scale | Standard Deviation 3.7 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 57 | -0.1 Scores on a scale | Standard Deviation 4.6 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 85 | 1.6 Scores on a scale | Standard Deviation 2.6 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 29 | 2.0 Scores on a scale | Standard Deviation 2.9 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 29 | -0.9 Scores on a scale | Standard Deviation 2.5 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 57 | -1.3 Scores on a scale | Standard Deviation 5.3 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 29 | 0.3 Scores on a scale | Standard Deviation 2.1 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 57 | 0.2 Scores on a scale | Standard Deviation 1.9 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 85 | -0.1 Scores on a scale | Standard Deviation 2.8 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 29 | 3.4 Scores on a scale | Standard Deviation 3.7 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 57 | 2.9 Scores on a scale | Standard Deviation 2.9 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 85 | 2.9 Scores on a scale | Standard Deviation 3.2 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 29 | -0.8 Scores on a scale | Standard Deviation 5.2 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 85 | -0.3 Scores on a scale | Standard Deviation 5.3 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 29 | 0.6 Scores on a scale | Standard Deviation 3.1 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 57 | 0.2 Scores on a scale | Standard Deviation 3 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 85 | 0.7 Scores on a scale | Standard Deviation 3 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 29 | -0.8 Scores on a scale | Standard Deviation 4.2 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 57 | -0.1 Scores on a scale | Standard Deviation 6.3 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 85 | -0.6 Scores on a scale | Standard Deviation 5.8 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 29 | -2.6 Scores on a scale | Standard Deviation 4.2 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 57 | -0.3 Scores on a scale | Standard Deviation 2.3 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 85 | -0.3 Scores on a scale | Standard Deviation 3 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 85 | -0.8 Scores on a scale | Standard Deviation 2.3 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 57 | -0.9 Scores on a scale | Standard Deviation 1.7 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 29 | -0.4 Scores on a scale | Standard Deviation 1.9 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 29 | -0.3 Scores on a scale | Standard Deviation 4.8 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Itch, Day 29 | -0.2 Scores on a scale | Standard Deviation 1.7 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | General symptoms, Day 85 | -0.4 Scores on a scale | Standard Deviation 2.2 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 85 | -1.3 Scores on a scale | Standard Deviation 4.9 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 29 | -0.5 Scores on a scale | Standard Deviation 2.3 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 85 | -3.1 Scores on a scale | Standard Deviation 4.6 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Emotional, Day 57 | -1.0 Scores on a scale | Standard Deviation 5.1 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Cognitive function, Day 57 | -0.4 Scores on a scale | Standard Deviation 2.6 |
| Placebo | Double-blind Phase: Change From Baseline in Quality of Life (QoL) as Determined by Primary Biliary Cirrhosis 40 (PBC-40) Scale | Fatigue, Day 57 | -3.5 Scores on a scale | Standard Deviation 6.3 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=121).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids | -4.489 Micromoles per liter | Standard Deviation 34.302 |
| OCA 25 mg | Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids | -3.018 Micromoles per liter | Standard Deviation 29.937 |
| OCA 50 mg | Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids | 33.526 Micromoles per liter | Standard Deviation 153.176 |
| Placebo | Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids | 0.525 Micromoles per liter | Standard Deviation 19.238 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=153).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale | PCS | -0.0 Scores on a scale | Standard Deviation 5.5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale | MCS | -2.2 Scores on a scale | Standard Deviation 7 |
| OCA 25 mg | Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale | MCS | -1.5 Scores on a scale | Standard Deviation 4.8 |
| OCA 25 mg | Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale | PCS | 0.1 Scores on a scale | Standard Deviation 5.7 |
| OCA 50 mg | Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale | PCS | 1.3 Scores on a scale | Standard Deviation 7.3 |
| OCA 50 mg | Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale | MCS | -1.2 Scores on a scale | Standard Deviation 10 |
| Placebo | Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale | PCS | 1.1 Scores on a scale | Standard Deviation 5.7 |
| Placebo | Double-blind Phase: Change From Baseline to Day 85 in Quality of Life as Determined by Short Form-36 (SF-36) Scale | MCS | 1.7 Scores on a scale | Standard Deviation 9.3 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=119).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids | -1.4 Micromoles per liter | Standard Deviation 38.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione | 1.4 Micromoles per liter | Standard Deviation 1.7 |
| OCA 25 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione | 1.3 Micromoles per liter | Standard Deviation 1.9 |
| OCA 25 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids | -1.1 Micromoles per liter | Standard Deviation 36.3 |
| OCA 50 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids | 0.5 Micromoles per liter | Standard Deviation 77.9 |
| OCA 50 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione | 1.2 Micromoles per liter | Standard Deviation 1.4 |
| Placebo | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Bile acids | -1.0 Micromoles per liter | Standard Deviation 28.3 |
| Placebo | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Bile Acids and Glutathion | Glutathione | 1.0 Micromoles per liter | Standard Deviation 2.3 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=114).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | -1.8 Milligrams per milliliter | Standard Deviation 7.9 |
| OCA 25 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | -3.7 Milligrams per milliliter | Standard Deviation 6.6 |
| OCA 50 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | 1.4 Milligrams per milliliter | Standard Deviation 9.4 |
| Placebo | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | 0.3 Milligrams per milliliter | Standard Deviation 3.7 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=119).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM | -0.71 Grams per liter | Standard Deviation 0.94 |
| OCA 25 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM | -0.58 Grams per liter | Standard Deviation 0.75 |
| OCA 50 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM | -0.95 Grams per liter | Standard Deviation 1.57 |
| Placebo | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM | 0.02 Grams per liter | Standard Deviation 0.61 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=112).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA | -0.06 Millimoles per liter | Standard Deviation 0.19 |
| OCA 25 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA | -0.01 Millimoles per liter | Standard Deviation 0.27 |
| OCA 50 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA | -0.07 Millimoles per liter | Standard Deviation 0.2 |
| Placebo | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA | 0.04 Millimoles per liter | Standard Deviation 0.25 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (165). Only those participants with data available at specified time points has been presented (n=119).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin | 51 Micrograms per liter | Standard Deviation 130 |
| OCA 25 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin | 36 Micrograms per liter | Standard Deviation 141 |
| OCA 50 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin | 72 Micrograms per liter | Standard Deviation 83 |
| Placebo | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin | -18 Micrograms per liter | Standard Deviation 119 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=119).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha | 3.0 Nanograms per liter | Standard Deviation 15.6 |
| OCA 25 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha | 1.7 Nanograms per liter | Standard Deviation 5.7 |
| OCA 50 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha | -0.2 Nanograms per liter | Standard Deviation 15.8 |
| Placebo | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha | 1.2 Nanograms per liter | Standard Deviation 4.2 |
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=120).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta | TNF-beta | -11.3 Picomoles per liter | Standard Deviation 25.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta | TGF-beta | 3.7 Picomoles per liter | Standard Deviation 22.1 |
| OCA 25 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta | TGF-beta | 3.4 Picomoles per liter | Standard Deviation 27.9 |
| OCA 25 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta | TNF-beta | 3.9 Picomoles per liter | Standard Deviation 6.1 |
| OCA 50 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta | TNF-beta | 2.2 Picomoles per liter | Standard Deviation 7.1 |
| OCA 50 mg | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta | TGF-beta | 14.0 Picomoles per liter | Standard Deviation 27.8 |
| Placebo | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta | TNF-beta | 1.1 Picomoles per liter | Standard Deviation 11.2 |
| Placebo | Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-beta and TGF-beta | TGF-beta | 0.1 Picomoles per liter | Standard Deviation 30 |
Secondary
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.
Time frame: Up to Day 85
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 34 Participants |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| OCA 25 mg | Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 1 Participants |
| OCA 25 mg | Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 47 Participants |
| OCA 50 mg | Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 41 Participants |
| OCA 50 mg | Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 5 Participants |
| Placebo | Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any TEAE | 32 Participants |
| Placebo | Double-blind Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Any SAE | 1 Participants |
Secondary
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.
Time frame: Baseline and at Days 15, 29, 57 and 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 15 | -0.42 Percent change | Standard Deviation 5.68 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 29 | -1.62 Percent change | Standard Deviation 4.52 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 57 | -0.69 Percent change | Standard Deviation 5.56 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 85 | -0.13 Percent change | Standard Deviation 5.03 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 29 | -0.73 Percent change | Standard Deviation 5.1 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 57 | -0.26 Percent change | Standard Deviation 4.83 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 85 | -0.11 Percent change | Standard Deviation 5.42 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 15 | -0.29 Percent change | Standard Deviation 5.71 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 57 | -2.00 Percent change | Standard Deviation 4.27 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 29 | -2.59 Percent change | Standard Deviation 5.69 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 85 | -2.82 Percent change | Standard Deviation 6.04 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 15 | -2.66 Percent change | Standard Deviation 4.7 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 85 | -0.82 Percent change | Standard Deviation 5.79 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 29 | -1.97 Percent change | Standard Deviation 4.78 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 15 | -0.41 Percent change | Standard Deviation 5.18 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Albumin Levels | Day 57 | -3.58 Percent change | Standard Deviation 6.9 |
Secondary
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.
Time frame: Baseline and at Days 15, 29, 57 and 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=164).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 15 | 14.6 Percent change | Standard Deviation 60.9 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 29 | -3.3 Percent change | Standard Deviation 41.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 57 | -2.9 Percent change | Standard Deviation 39.6 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 85 | 0.0 Percent change | Standard Deviation 49.6 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 29 | -11.8 Percent change | Standard Deviation 43.7 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 57 | -8.8 Percent change | Standard Deviation 44.1 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 85 | -12.2 Percent change | Standard Deviation 40 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 15 | -15.3 Percent change | Standard Deviation 38.1 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 57 | -18.7 Percent change | Standard Deviation 31.3 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 29 | 31.3 Percent change | Standard Deviation 276.8 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 85 | 10.0 Percent change | Standard Deviation 143.2 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 15 | -17.6 Percent change | Standard Deviation 35.4 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 85 | 3.7 Percent change | Standard Deviation 48.2 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 29 | 12.2 Percent change | Standard Deviation 39.3 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 15 | 2.7 Percent change | Standard Deviation 38.2 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Conjugated (Direct) Bilirubin | Day 57 | 1.4 Percent change | Standard Deviation 32.8 |
Secondary
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.
Time frame: Baseline and at Days 15, 29, 57 and 85
Population: ITT Population (N=165). Only those participants with data available at specified timepoints has been presented (n=164).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 15 | -6 Percent change | Standard Deviation 42 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 29 | -20.8 Percent change | Standard Deviation 14.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 57 | -26.0 Percent change | Standard Deviation 15.4 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 85 | -23.3 Percent change | Standard Deviation 17.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 15 | -13.5 Percent change | Standard Deviation 12.8 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 29 | -16 Percent change | Standard Deviation 22 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 57 | -19 Percent change | Standard Deviation 22 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 85 | -17 Percent change | Standard Deviation 21 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 15 | -11 Percent change | Standard Deviation 61 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 29 | -25 Percent change | Standard Deviation 28 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 57 | -31 Percent change | Standard Deviation 23 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 85 | -28 Percent change | Standard Deviation 27 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 15 | -35 Percent change | Standard Deviation 14 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 29 | -48 Percent change | Standard Deviation 19 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 57 | -53 Percent change | Standard Deviation 26 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 85 | -48 Percent change | Standard Deviation 30 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 29 | -17 Percent change | Standard Deviation 18 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 15 | -26 Percent change | Standard Deviation 18 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 85 | -63 Percent change | Standard Deviation 24 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 85 | -35 Percent change | Standard Deviation 22 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 57 | -64 Percent change | Standard Deviation 24 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 29 | -33 Percent change | Standard Deviation 18 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 57 | -22.0 Percent change | Standard Deviation 17.2 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 57 | -32 Percent change | Standard Deviation 33 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 15 | -14 Percent change | Standard Deviation 18 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 57 | -13 Percent change | Standard Deviation 30 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 85 | -24.0 Percent change | Standard Deviation 18.8 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 29 | -23.4 Percent change | Standard Deviation 12.3 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 15 | -43 Percent change | Standard Deviation 14 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 85 | -16 Percent change | Standard Deviation 20 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 29 | -61 Percent change | Standard Deviation 15 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 15 | -17.3 Percent change | Standard Deviation 9.8 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 29 | -13 Percent change | Standard Deviation 26 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 15 | 13 Percent change | Standard Deviation 119 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 29 | -63 Percent change | Standard Deviation 16 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 57 | -15 Percent change | Standard Deviation 27 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 85 | -9 Percent change | Standard Deviation 38 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 85 | -57 Percent change | Standard Deviation 31 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 15 | 12 Percent change | Standard Deviation 176 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 29 | -29 Percent change | Standard Deviation 27 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 57 | -67 Percent change | Standard Deviation 18 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 57 | -35 Percent change | Standard Deviation 24 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 85 | -21 Percent change | Standard Deviation 49 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 15 | -16.1 Percent change | Standard Deviation 21.9 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 29 | -25.0 Percent change | Standard Deviation 17.5 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 15 | -49 Percent change | Standard Deviation 12 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 57 | -29.0 Percent change | Standard Deviation 18.6 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 85 | -20.0 Percent change | Standard Deviation 27.4 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 85 | 7 Percent change | Standard Deviation 28 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 85 | -0 Percent change | Standard Deviation 23 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 57 | -0.9 Percent change | Standard Deviation 17.1 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 15 | -2.6 Percent change | Standard Deviation 10.8 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 29 | 1 Percent change | Standard Deviation 24 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 57 | 20 Percent change | Standard Deviation 95 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 15 | -1 Percent change | Standard Deviation 15 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 29 | -4.6 Percent change | Standard Deviation 12.4 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 15 | 3 Percent change | Standard Deviation 23 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 29 | 1 Percent change | Standard Deviation 31 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, Day 29 | 2 Percent change | Standard Deviation 27 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 57 | 8 Percent change | Standard Deviation 43 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, Day 57 | 2 Percent change | Standard Deviation 20 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 15 | 6 Percent change | Standard Deviation 30 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, Day 85 | -2.6 Percent change | Standard Deviation 12.4 |
| Placebo | Double-blind Phase: Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, Day 85 | -0 Percent change | Standard Deviation 35 |
p-value: <0.0005Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline and Up to Day 85
Population: ITT Population (N=165). Only those participants with data available at specified time points has been presented (n=126).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | Double-blind Phase: Percent Change From Baseline Values for FGF19 | 161.0 Percent change | Standard Deviation 148.7 |
| OCA 25 mg | Double-blind Phase: Percent Change From Baseline Values for FGF19 | 464.7 Percent change | Standard Deviation 1419.1 |
| OCA 50 mg | Double-blind Phase: Percent Change From Baseline Values for FGF19 | 3029.2 Percent change | Standard Deviation 13234 |
| Placebo | Double-blind Phase: Percent Change From Baseline Values for FGF19 | 75.9 Percent change | Standard Deviation 250.6 |
Secondary
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
Time frame: Baseline and at 3, 6, 9 and 12 Months
Population: ITT Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale | Baseline, PCS | 45.7 Scores on a scale | Standard Deviation 10.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale | 12 Months, PCS | 44.1 Scores on a scale | Standard Deviation 11.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale | Baseline, MCS | 49.4 Scores on a scale | Standard Deviation 10.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Absolute Values of Quality of Life as Determined by SF-36 Scale | 12 Months, MCS | 48.3 Scores on a scale | Standard Deviation 11.2 |
Secondary
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.
Time frame: Baseline and at 6 and 12 months
Population: Safety Population (N=78). Only those participants with data available at specified time points has been presented (n=66).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | General symptoms, 6 months | 0.3 Scores on a scale | Standard Deviation 3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | General symptoms, 12 months | 0.3 Scores on a scale | Standard Deviation 2.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | Itch, 6 months | 1.2 Scores on a scale | Standard Deviation 3.6 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | Itch, 12 months | 0.5 Scores on a scale | Standard Deviation 3.3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | Fatigue, 6 months | -1.1 Scores on a scale | Standard Deviation 5.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | Fatigue, 12 months | -1.7 Scores on a scale | Standard Deviation 5.4 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | Cognitive function, 6 months | 0.1 Scores on a scale | Standard Deviation 3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | Cognitive function, 12 months | -0.4 Scores on a scale | Standard Deviation 3.3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | Emotional, 6 months | -0.4 Scores on a scale | Standard Deviation 4.4 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Change From Baseline in Quality of Life as Determined by PBC-40 Scale | Emotional, 12 months | -1.0 Scores on a scale | Standard Deviation 5.4 |
Secondary
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.
Time frame: Baseline and at 3, 6, 9 and 12 Months
Population: Safety Population (N=78) comprised of all randomized participants who received at least 1 dose of investigational product. Only those participants with data available at specified timepoints has been presented (n=69).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, 3-Month | -22.2 Percent change | Standard Deviation 18.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, 6-Month | -23.7 Percent change | Standard Deviation 22.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, 9-Month | -25.3 Percent change | Standard Deviation 22.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALP, 12-Month | -26.5 Percent change | Standard Deviation 22 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, 3-Month | 2.3 Percent change | Standard Deviation 29.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, 6-Month | -1.2 Percent change | Standard Deviation 26.6 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, 9-Month | -4.7 Percent change | Standard Deviation 27.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | AST, 12-Month | -0.7 Percent change | Standard Deviation 27.1 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, 3-Month | -17.8 Percent change | Standard Deviation 28.5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, 6-Month | -22.9 Percent change | Standard Deviation 26.5 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, 9-Month | -23.3 Percent change | Standard Deviation 40.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | ALT, 12-Month | -20.7 Percent change | Standard Deviation 26.4 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, 3-Month | -52.4 Percent change | Standard Deviation 25.4 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, 6-Month | -57.5 Percent change | Standard Deviation 33.3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, 9-Month | -60.9 Percent change | Standard Deviation 24.9 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Serum ALP, AST, ALT and GGT Levels | GGT, 12-Month | -60.4 Percent change | Standard Deviation 25.5 |
Secondary
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.
Time frame: Baseline and at 3, 6, 9 and 12 Months
Population: Safety Population (N=78). Only those participants with data available at specified timepoints has been presented (n=69)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin | Direct bilirubin, 3-Month | 19.6 Percent change | Standard Deviation 46.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin | Direct bilirubin, 6-Month | 24.6 Percent change | Standard Deviation 53.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin | Direct bilirubin, 9-Month | 15.2 Percent change | Standard Deviation 44.3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin | Direct bilirubin, 12-Month | 23.1 Percent change | Standard Deviation 68.3 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin | Total bilirubin, 3-Month | -17.0 Percent change | Standard Deviation 28 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin | Total bilirubin, 6-Month | -11.6 Percent change | Standard Deviation 25.2 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin | Total bilirubin, 9-Month | -18.3 Percent change | Standard Deviation 29.7 |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Mean Percent Change From Baseline in Total and Conjugated (Direct) Bilirubin | Total bilirubin, 12-Month | -8.9 Percent change | Standard Deviation 35.8 |
Secondary
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.
Time frame: Up to 12 Months
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Number of Participants With TEAEs and SAEs | Any SAE | 5 Participants |
| Obeticholic Acid (OCA) 10 Milligrams (mg) | LTSE Phase: Number of Participants With TEAEs and SAEs | Any TEAE | 76 Participants |