A Phase 2 interventional study of INT-747 and Ursodeoxycholic Acid (URSO) in Liver Cirrhosis, Biliary, sponsored by Intercept Pharmaceuticals. Terminated at 32 sites in 8 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-02-06.
Sponsored by Intercept Pharmaceuticals · Phase 2, Interventional, and Treatment
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.
None provided
1,642 studies on the registry are indexed under Liver Cirrhosis; 358 are open to participants now.
This study's enrollment of 165 is above the median of 72 across 995 interventional studies indexed under Liver Cirrhosis.
Browse Liver Cirrhosis studies →Intercept Pharmaceuticals is the lead sponsor of 21 studies on the registry; none are open to participants now.
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Proven or likely PBC, as demonstrated by the patient presenting with at least 2 of the following 3 diagnostic factors:
Exclusion Criteria:
INT-747 10 mg once daily in combination with URSO for 12 weeks.
Drug: INT-747 · Drug: Ursodeoxycholic Acid (URSO)
INT-747 25 mg once daily in combination with URSO for 12 weeks.
Drug: INT-747 · Drug: Ursodeoxycholic Acid (URSO)
INT-747 50 mg once daily in combination with URSO for 12 weeks.
Drug: INT-747 · Drug: Ursodeoxycholic Acid (URSO)
Placebo once daily in combination with URSO for 12 weeks.
Drug: INT-747 · Drug: Ursodeoxycholic Acid (URSO) · Drug: Placebo
Once a day (QD) by mouth (PO)
Also known as: Obeticholic acid (OCA), 6-ECDCA
Stable dose for at least 6 months prior to screening. Dose as prescribed by physician.
Also known as: URSO, UDCA
Placebo
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
This was an international, multi-center, randomized, double-blind, placebo-controlled, multi-dose study with the majority of the sites being academic centers.
| Milestone | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo | LTSE OCA Total |
|---|---|---|---|---|---|
| Started | 38 | 48 | 41 | 38 | 0 |
| Completed | 32 | 42 | 25 | 37 | 0 |
| Not completed | 6 | 6 | 16 | 1 | 0 |
| Withdrew: Adverse event | 5 | 5 | 12 | 1 | 0 |
| Withdrew: Elevated conjugated (direct) bilirubin | 1 | 0 | 2 | 0 | 0 |
| Withdrew: Elevated aspartate transaminase (ast)/ alanine transaminase (alt) levels | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 1 | 0 | 0 | 0 |
| Milestone | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo | LTSE OCA Total |
|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 78 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 78 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 14 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 2 |
| Withdrew: Protocol violation | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Other | 0 | 0 | 0 | 0 | 2 |
| Withdrew: Other: study stopped by sponsor due to administrative reasons | 0 | 0 | 0 | 0 | 59 |
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.
| Percent change | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Double-blind Phase: Percent Change From Baseline in Serum Alkaline Phosphatase (ALP) | -23.7 ± 17.8 | -24.7 ± 17.9 | -21.0 ± 27.6 | -2.6 ± 12.5 |
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).
| Units per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| ALP, Baseline | 294.4 ± 149.4 | 290.0 ± 123.6 | 289.5 ± 106.2 | 275.2 ± 102.7 |
| ALP, Day 15 | 247.6 ± 117.9 | 239.3 ± 113.6 | 231.2 ± 87.5 | 269.2 ± 105.6 |
| ALP, Day 29 | 227.2 ± 105.0 | 219.2 ± 100.5 | 216.1 ± 90.5 | 266.1 ± 118.0 |
| ALP, Day 57 | 212.6 ± 98.9 | 231.7 ± 177.6 | 189.2 ± 67.5 | 271.5 ± 123.0 |
| ALP, Day 85 | 219.0 ± 113.5 | 225.0 ± 169.1 | 227.9 ± 115.9 | 270.7 ± 118.7 |
| AST, Baseline | 49 ± 22 | 44 ± 23 | 48 ± 24 | 42 ± 19 |
| AST, Day 15 | 44 ± 23 | 38 ± 19 | 47 ± 34 | 41 ± 17 |
| AST, Day 29 | 37 ± 13 | 36 ± 19 | 43 ± 28 | 42 ± 20 |
| AST, Day 57 | 36 ± 14 | 40 ± 45 | 37 ± 17 | 45 ± 28 |
| AST, Day 85 | 40 ± 23 | 37 ± 25 | 41 ± 24 | 41 ± 17 |
| ALT, Baseline | 51 ± 29 | 51 ± 36 | 53 ± 35 | 47 ± 26 |
| ALT, Day 15 | 40 ± 20 | 37 ± 28 | 49 ± 49 | 48 ± 24 |
| ALT, Day 29 | 35 ± 15 | 32 ± 25 | 43 ± 40 | 46 ± 25 |
| ALT, Day 57 | 32 ± 16 | 39 ± 70 | 34 ± 23 | 49 ± 29 |
| ALT, Day 85 | 34 ± 20 | 34 ± 38 | 39 ± 32 | 45 ± 24 |
| GGT, Baseline | 228 ± 212 | 273 ± 267 | 231 ± 182 | 189 ± 139 |
| GGT, Day 15 | 137 ± 119 | 155 ± 197 | 108 ± 88 | 190 ± 141 |
| GGT, Day 29 | 108 ± 92 | 109 ± 153 | 93 ± 90 | 196 ± 158 |
| GGT, Day 57 | 96 ± 91 | 104 ± 189 | 76 ± 86 | 195 ± 165 |
| GGT, Day 85 | 107 ± 124 | 115 ± 178 | 95 ± 89 | 209 ± 170 |
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.
| Percent change | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| ALP, Day 15 | -13.5 ± 12.8 | -17.3 ± 9.8 | -16.1 ± 21.9 | -2.6 ± 10.8 |
| ALP, Day 29 | -20.8 ± 14.2 | -23.4 ± 12.3 | -25.0 ± 17.5 | -4.6 ± 12.4 |
| ALP, Day 57 | -26.0 ± 15.4 | -22.0 ± 17.2 | -29.0 ± 18.6 | -0.9 ± 17.1 |
| ALP, Day 85 | -23.3 ± 17.1 | -24.0 ± 18.8 | -20.0 ± 27.4 | -2.6 ± 12.4 |
| AST, Day 15 | -6 ± 42 | -14 ± 18 | 13 ± 119 | 3 ± 23 |
| AST, Day 29 | -16 ± 22 | -17 ± 18 | -13 ± 26 | 2 ± 27 |
| AST, Day 57 | -19 ± 22 | -13 ± 30 | -15 ± 27 | 20 ± 95 |
| AST, Day 85 | -17 ± 21 | -16 ± 20 | -9 ± 38 | -0 ± 23 |
| ALT, Day 15 | -11 ± 61 | -26 ± 18 | 12 ± 176 | 6 ± 30 |
| ALT, Day 29 | -25 ± 28 | -33 ± 18 | -29 ± 27 | 1 ± 31 |
| ALT, Day 57 | -31 ± 23 | -32 ± 33 | -35 ± 24 | 8 ± 43 |
| ALT, Day 85 | -28 ± 27 | -35 ± 22 | -21 ± 49 | -0 ± 35 |
| GGT, Day 15 | -35 ± 14 | -43 ± 14 | -49 ± 12 | -1 ± 15 |
| GGT, Day 29 | -48 ± 19 | -61 ± 15 | -63 ± 16 | 1 ± 24 |
| GGT, Day 57 | -53 ± 26 | -64 ± 24 | -67 ± 18 | 2 ± 20 |
| GGT, Day 85 | -48 ± 30 | -63 ± 24 | -57 ± 31 | 7 ± 28 |
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.
| Percent change | LTSE OCA Total |
|---|---|
| ALP, 3-Month | -22.2 ± 18.2 |
| ALP, 6-Month | -23.7 ± 22.7 |
| ALP, 9-Month | -25.3 ± 22.2 |
| ALP, 12-Month | -26.5 ± 22.0 |
| AST, 3-Month | 2.3 ± 29.2 |
| AST, 6-Month | -1.2 ± 26.6 |
| AST, 9-Month | -4.7 ± 27.1 |
| AST, 12-Month | -0.7 ± 27.1 |
| ALT, 3-Month | -17.8 ± 28.5 |
| ALT, 6-Month | -22.9 ± 26.5 |
| ALT, 9-Month | -23.3 ± 40.7 |
| ALT, 12-Month | -20.7 ± 26.4 |
| GGT, 3-Month | -52.4 ± 25.4 |
| GGT, 6-Month | -57.5 ± 33.3 |
| GGT, 9-Month | -60.9 ± 24.9 |
| GGT, 12-Month | -60.4 ± 25.5 |
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).
| Grams per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Baseline | 40.14 ± 4.66 | 41.17 ± 3.85 | 42.41 ± 2.77 | 42.03 ± 3.23 |
| Day 15 | 39.84 ± 4.33 | 41.12 ± 3.59 | 41.15 ± 3.05 | 41.84 ± 3.38 |
| Day 29 | 40.01 ± 3.38 | 40.94 ± 3.74 | 41.05 ± 3.64 | 41.21 ± 3.50 |
| Day 57 | 40.29 ± 3.65 | 41.04 ± 3.90 | 41.76 ± 3.00 | 40.50 ± 4.33 |
| Day 85 | 39.95 ± 4.19 | 41.09 ± 4.01 | 41.24 ± 3.86 | 41.69 ± 4.05 |
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.
| Percent change | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Day 15 | -0.42 ± 5.68 | -0.29 ± 5.71 | -2.66 ± 4.70 | -0.41 ± 5.18 |
| Day 29 | -1.62 ± 4.52 | -0.73 ± 5.10 | -2.59 ± 5.69 | -1.97 ± 4.78 |
| Day 57 | -0.69 ± 5.56 | -0.26 ± 4.83 | -2.00 ± 4.27 | -3.58 ± 6.90 |
| Day 85 | -0.13 ± 5.03 | -0.11 ± 5.42 | -2.82 ± 6.04 | -0.82 ± 5.79 |
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).
| Micromoles per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Baseline | 4.2 ± 3.1 | 3.9 ± 2.4 | 4.7 ± 3.3 | 3.6 ± 2.8 |
| Day 15 | 4.9 ± 5.0 | 3.1 ± 2.2 | 3.3 ± 2.2 | 3.4 ± 2.4 |
| Day 29 | 3.3 ± 2.6 | 3.3 ± 2.6 | 5.6 ± 14.4 | 3.7 ± 2.8 |
| Day 57 | 3.4 ± 3.1 | 3.4 ± 2.6 | 3.0 ± 1.6 | 3.5 ± 3.0 |
| Day 85 | 3.9 ± 3.8 | 3.2 ± 2.7 | 5.5 ± 8.5 | 3.6 ± 3.2 |
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.
| Percent change | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Day 15 | 14.6 ± 60.9 | -15.3 ± 38.1 | -17.6 ± 35.4 | 2.7 ± 38.2 |
| Day 29 | -3.3 ± 41.2 | -11.8 ± 43.7 | 31.3 ± 276.8 | 12.2 ± 39.3 |
| Day 57 | -2.9 ± 39.6 | -8.8 ± 44.1 | -18.7 ± 31.3 | 1.4 ± 32.8 |
| Day 85 | 0.0 ± 49.6 | -12.2 ± 40.0 | 10.0 ± 143.2 | 3.7 ± 48.2 |
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.
| Percent change | LTSE OCA Total |
|---|---|
| Direct bilirubin, 3-Month | 19.6 ± 46.2 |
| Direct bilirubin, 6-Month | 24.6 ± 53.2 |
| Direct bilirubin, 9-Month | 15.2 ± 44.3 |
| Direct bilirubin, 12-Month | 23.1 ± 68.3 |
| Total bilirubin, 3-Month | -17.0 ± 28.0 |
| Total bilirubin, 6-Month | -11.6 ± 25.2 |
| Total bilirubin, 9-Month | -18.3 ± 29.7 |
| Total bilirubin, 12-Month | -8.9 ± 35.8 |
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.
| Scores on a scale | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Double-blind Phase: Change From Baseline in Enhanced Liver Fibrosis (ELF) Score | -0.095 ± 0.593 | 0.008 ± 0.561 | 0.124 ± 0.685 | -0.212 ± 0.627 |
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.
| Nanograms per milliliter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| HA | -6.771 ± 59.677 | 12.287 ± 73.090 | 20.117 ± 97.056 | -21.359 ± 69.389 |
| P3NP | -0.503 ± 3.017 | -0.468 ± 2.389 | 1.858 ± 6.547 | -0.943 ± 3.206 |
| TIMP-1 | 15.341 ± 218.71 | -18.409 ± 191.768 | 43.921 ± 222.930 | -65.196 ± 257.295 |
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).
| Milligrams per milliliter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Baseline | 7.9 ± 7.5 | 7.8 ± 8.9 | 5.2 ± 5.6 | 5.1 ± 4.6 |
| Day 85 | 6.4 ± 7.2 | 4.0 ± 4.4 | 6.0 ± 13.2 | 6.0 ± 5.8 |
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.
| Milligrams per milliliter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: C-reactive Protein | -1.8 ± 7.9 | -3.7 ± 6.6 | 1.4 ± 9.4 | 0.3 ± 3.7 |
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).
| Millimoles per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Baseline | 0.58 ± 0.23 | 0.55 ± 0.24 | 0.62 ± 0.23 | 0.54 ± 0.26 |
| Day 85 | 0.49 ± 0.24 | 0.51 ± 0.19 | 0.55 ± 0.25 | 0.56 ± 0.19 |
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.
| Millimoles per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: NEFA | -0.06 ± 0.19 | -0.01 ± 0.27 | -0.07 ± 0.20 | 0.04 ± 0.25 |
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).
| Nanograms per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Baseline | 15.6 ± 7.1 | 13.8 ± 4.4 | 16.1 ± 11.7 | 11.4 ± 3.2 |
| Day 85 | 18.1 ± 14.8 | 15.4 ± 7.3 | 16.2 ± 12.1 | 13.6 ± 4.5 |
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.
| Nanograms per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: TNF-alpha | 3.0 ± 15.6 | 1.7 ± 5.7 | -0.2 ± 15.8 | 1.2 ± 4.2 |
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).
| Picomoles per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| TNF-beta, Baseline | 13.1 ± 14.8 | 10.8 ± 12.2 | 8.7 ± 10.4 | 8.8 ± 12.0 |
| TNF-beta, Day 85 | 11.0 ± 7.8 | 14.5 ± 17.0 | 6.7 ± 7.6 | 10.9 ± 17.3 |
| TGF-beta, Baseline | 35.6 ± 22.0 | 37.0 ± 23.3 | 26.2 ± 22.9 | 36.4 ± 25.3 |
| TGF-beta, Day 85 | 39.2 ± 22.9 | 41.0 ± 25.7 | 40.4 ± 22.3 | 30.1 ± 23.1 |
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.
| Picomoles per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| TNF-beta | -11.3 ± 25.1 | 3.9 ± 6.1 | 2.2 ± 7.1 | 1.1 ± 11.2 |
| TGF-beta | 3.7 ± 22.1 | 3.4 ± 27.9 | 14.0 ± 27.8 | 0.1 ± 30.0 |
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).
| Micromoles per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Bile acids, Baseline | 36.9 ± 31.7 | 29.5 ± 26.1 | 36.0 ± 48.9 | 27.6 ± 32.3 |
| Bile acids, Day 85 | 37.8 ± 47.3 | 30.2 ± 42.9 | 34.6 ± 57.2 | 26.2 ± 29.2 |
| Glutathione, Baseline | 3.7 ± 1.3 | 4.0 ± 1.9 | 3.4 ± 1.6 | 3.8 ± 1.8 |
| Glutathione, Day 85 | 5.0 ± 2.1 | 5.3 ± 1.9 | 4.8 ± 2.0 | 4.8 ± 1.9 |
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.
| Micromoles per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Bile acids | -1.4 ± 38.7 | -1.1 ± 36.3 | 0.5 ± 77.9 | -1.0 ± 28.3 |
| Glutathione | 1.4 ± 1.7 | 1.3 ± 1.9 | 1.2 ± 1.4 | 1.0 ± 2.3 |
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).
| Grams per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Baseline | 4.31 ± 2.12 | 3.13 ± 1.95 | 3.82 ± 3.35 | 3.06 ± 1.73 |
| Day 85 | 3.73 ± 1.91 | 2.62 ± 1.76 | 3.02 ± 2.14 | 2.97 ± 1.61 |
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.
| Grams per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: IgM | -0.71 ± 0.94 | -0.58 ± 0.75 | -0.95 ± 1.57 | 0.02 ± 0.61 |
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).
| Micrograms per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Baseline | 305 ± 175 | 279 ± 118 | 286 ± 122 | 264 ± 130 |
| Day 85 | 335 ± 187 | 318 ± 131 | 350 ± 170 | 245 ± 115 |
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.
| Micrograms per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Double-blind Phase: Change From Baseline Values for Biomarkers of Hepatic Inflammation: Osteopontin | 51 ± 130 | 36 ± 141 | 72 ± 83 | -18 ± 119 |
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).
| Micromoles per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Baseline | 11.011 ± 9.071 | 10.013 ± 12.860 | 16.048 ± 28.325 | 6.350 ± 9.524 |
| Day 85 | 9.516 ± 14.945 | 5.948 ± 15.590 | 23.935 ± 54.351 | 8.796 ± 11.557 |
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.
| Micromoles per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Double-blind Phase: Change From Baseline in Total Endogenous Bile Acids | -4.489 ± 34.302 | -3.018 ± 29.937 | 33.526 ± 153.176 | 0.525 ± 19.238 |
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).
| Nanograms per liter | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Baseline | 102.9 ± 60.7 | 104.1 ± 64.5 | 115.7 ± 122.4 | 84.1 ± 56.1 |
| Day 85 | 248.2 ± 221.3 | 386.9 ± 443.9 | 2269.7 ± 9874.8 | 95.6 ± 65.6 |
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.
| Percent change | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Double-blind Phase: Percent Change From Baseline Values for FGF19 | 161.0 ± 148.7 | 464.7 ± 1419.1 | 3029.2 ± 13234.0 | 75.9 ± 250.6 |
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.
| Scores on a scale | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| PCS | -0.0 ± 5.5 | 0.1 ± 5.7 | 1.3 ± 7.3 | 1.1 ± 5.7 |
| MCS | -2.2 ± 7.0 | -1.5 ± 4.8 | -1.2 ± 10.0 | 1.7 ± 9.3 |
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
| Scores on a scale | LTSE OCA Total |
|---|---|
| Baseline, PCS | 45.7 ± 10.7 |
| 12 Months, PCS | 44.1 ± 11.2 |
| Baseline, MCS | 49.4 ± 10.2 |
| 12 Months, MCS | 48.3 ± 11.2 |
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.
| Scores on a scale | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| General symptoms, Day 29 | -0.4 ± 2.4 | -0.9 ± 2.5 | 0.3 ± 2.1 | -0.4 ± 1.9 |
| General symptoms, Day 57 | 0.1 ± 2.7 | -0.5 ± 2.2 | 0.2 ± 1.9 | -0.3 ± 2.3 |
| General symptoms, Day 85 | 0.3 ± 2.9 | 0.0 ± 2.8 | -0.1 ± 2.8 | -0.4 ± 2.2 |
| Itch, Day 29 | 0.6 ± 2.2 | 2.0 ± 2.9 | 3.4 ± 3.7 | -0.2 ± 1.7 |
| Itch, Day 57 | 0.6 ± 2.7 | 2.0 ± 3.0 | 2.9 ± 2.9 | -0.9 ± 1.7 |
| Itch, Day 85 | 1.1 ± 2.6 | 1.6 ± 2.6 | 2.9 ± 3.2 | -0.8 ± 2.3 |
| Fatigue, Day 29 | -0.5 ± 4.6 | -1.3 ± 5.1 | -0.8 ± 5.2 | -2.6 ± 4.2 |
| Fatigue, Day 57 | -0.3 ± 4.7 | -0.6 ± 5.0 | -1.3 ± 5.3 | -3.5 ± 6.3 |
| Fatigue, Day 85 | -0.4 ± 4.3 | 0.4 ± 4.6 | -0.3 ± 5.3 | -3.1 ± 4.6 |
| Cognitive function, Day 29 | -0.1 ± 2.0 | -0.5 ± 2.0 | 0.6 ± 3.1 | -0.5 ± 2.3 |
| Cognitive function, Day 57 | -0.3 ± 2.8 | -0.2 ± 2.8 | 0.2 ± 3.0 | -0.4 ± 2.6 |
| Cognitive function, Day 85 | -0.2 ± 2.5 | 0.0 ± 3.1 | 0.7 ± 3.0 | -0.3 ± 3.0 |
| Emotional, Day 29 | 0.7 ± 4.4 | -1.1 ± 3.6 | -0.8 ± 4.2 | -0.3 ± 4.8 |
| Emotional, Day 57 | 0.7 ± 5.0 | -0.1 ± 4.6 | -0.1 ± 6.3 | -1.0 ± 5.1 |
| Emotional, Day 85 | 0.5 ± 4.6 | -0.6 ± 3.7 | -0.6 ± 5.8 | -1.3 ± 4.9 |
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.
| Scores on a scale | LTSE OCA Total |
|---|---|
| General symptoms, 6 months | 0.3 ± 3.0 |
| General symptoms, 12 months | 0.3 ± 2.7 |
| Itch, 6 months | 1.2 ± 3.6 |
| Itch, 12 months | 0.5 ± 3.3 |
| Fatigue, 6 months | -1.1 ± 5.1 |
| Fatigue, 12 months | -1.7 ± 5.4 |
| Cognitive function, 6 months | 0.1 ± 3.0 |
| Cognitive function, 12 months | -0.4 ± 3.3 |
| Emotional, 6 months | -0.4 ± 4.4 |
| Emotional, 12 months | -1.0 ± 5.4 |
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
| Scores on a scale | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Total score, Day 29 | 2.6 ± 3.4 | 3.0 ± 4.7 | 4.4 ± 5.4 | -0.7 ± 2.9 |
| Total score, Day 57 | 1.8 ± 4.5 | 2.6 ± 3.9 | 2.9 ± 3.3 | -1.8 ± 3.0 |
| Total score, Day 85 | 1.3 ± 3.8 | 1.7 ± 4.0 | 4.2 ± 5.1 | -1.5 ± 3.8 |
| Duration, Day 29 | 0.3 ± 0.9 | 0.7 ± 1.5 | 1.2 ± 1.6 | 0.1 ± 1.0 |
| Duration, Day 57 | 0.4 ± 1.3 | 0.6 ± 1.1 | 0.5 ± 1.0 | -0.3 ± 0.7 |
| Duration, Day 85 | 0.2 ± 0.8 | 0.4 ± 1.1 | 0.8 ± 1.2 | -0.2 ± 0.8 |
| Degree, Day 29 | 0.5 ± 0.8 | 0.6 ± 1.0 | 1.0 ± 1.1 | 0.0 ± 0.6 |
| Degree, Day 57 | 0.3 ± 1.0 | 0.7 ± 1.0 | 0.7 ± 1.0 | -0.2 ± 0.8 |
| Degree, Day 85 | 0.4 ± 0.9 | 0.6 ± 1.0 | 0.9 ± 1.1 | -0.2 ± 0.7 |
| Direction, Day 29 | 0.5 ± 1.1 | 0.2 ± 1.5 | -0.2 ± 1.6 | -0.3 ± 1.2 |
| Direction, Day 57 | 0.0 ± 1.3 | 0.1 ± 1.5 | -0.2 ± 1.4 | -0.7 ± 1.4 |
| Direction, Day 85 | -0.2 ± 1.5 | -0.2 ± 1.5 | 0.1 ± 1.4 | -0.5 ± 1.5 |
| Disability, Day 29 | 0.7 ± 1.2 | 0.7 ± 1.2 | 1.3 ± 1.5 | -0.3 ± 0.9 |
| Disability, Day 57 | 0.4 ± 1.1 | 0.6 ± 1.1 | 0.8 ± 1.2 | -0.4 ± 1.1 |
| Disability, Day 85 | 0.3 ± 1.2 | 0.6 ± 1.2 | 1.0 ± 1.4 | -0.4 ± 1.2 |
| Distribution, Day 29 | 0.6 ± 0.9 | 0.8 ± 1.5 | 1.4 ± 1.6 | -0.2 ± 0.9 |
| Distribution, Day 57 | 0.5 ± 1.1 | 0.8 ± 1.2 | 1.4 ± 1.3 | -0.2 ± 0.8 |
| Distribution, Day 85 | 0.6 ± 0.9 | 0.8 ± 1.2 | 1.2 ± 1.5 | -0.2 ± 1.0 |
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.
| Participants | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Any TEAE | 34 | 47 | 41 | 32 |
| Any SAE | 0 | 1 | 5 | 1 |
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.
| Scores on a scale | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo |
|---|---|---|---|---|
| Day 29 | 11.5 ± 19.5 | 17.8 ± 26.3 | 22.8 ± 33.2 | -2.6 ± 16.3 |
| Day 57 | 7.0 ± 25.7 | 15.4 ± 24.7 | 13.7 ± 25.7 | -10.7 ± 19.6 |
| Day 85 | 6.5 ± 22.2 | 12.9 ± 24.5 | 17.2 ± 28.9 | -5.8 ± 20.5 |
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.
| Participants | LTSE OCA Total |
|---|---|
| Any TEAE | 76 |
| Any SAE | 5 |
Collected over AEs and SAEs were collected Up to Day 85 for Double-blind phase and up to 12 Months for LTSE phase.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Obeticholic Acid (OCA) 10 Milligrams (mg) | 0/38 (0%) | 0/38 (0%) | 34/38 (89.5%) |
| OCA 25 mg | 0/48 (0%) | 1/48 (2.1%) | 47/48 (97.9%) |
| OCA 50 mg | 0/41 (0%) | 5/41 (12.2%) | 41/41 (100%) |
| Placebo | 0/38 (0%) | 1/38 (2.6%) | 32/38 (84.2%) |
| LTSE OCA Total | 0/78 (0%) | 5/78 (6.4%) | 76/78 (97.4%) |
| Event | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo | LTSE OCA Total |
|---|---|---|---|---|---|
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/38 | 0/48 | 0/41 | 1/38 | 0/78 |
| Angina pectorisCardiac disorders | 0/38 | 0/48 | 1/41 | 0/38 | 0/78 |
| Gastrointestinal haemorrhageGastrointestinal disorders | 0/38 | 0/48 | 1/41 | 0/38 | 0/78 |
| Chest painGeneral disorders | 0/38 | 0/48 | 1/41 | 0/38 | 0/78 |
| Biliary cirrhosis primaryHepatobiliary disorders | 0/38 | 0/48 | 1/41 | 0/38 | 0/78 |
| JaundiceHepatobiliary disorders | 0/38 | 0/48 | 1/41 | 0/38 | 0/78 |
| AngioedemaSkin and subcutaneous tissue disorders | 0/38 | 0/48 | 1/41 | 0/38 | 0/78 |
| Salivary gland neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/38 | 1/48 | 0/41 | 0/38 | 0/78 |
| Uterine leiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/38 | 0/48 | 0/41 | 0/38 | 1/78 |
| AtelectasisRespiratory, thoracic and mediastinal disorders | 0/38 | 0/48 | 0/41 | 0/38 | 1/78 |
| Event | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo | LTSE OCA Total |
|---|---|---|---|---|---|
| PruritusSkin and subcutaneous tissue disorders | 18/38 | 41/48 | 33/41 | 19/38 | 68/78 |
| FatigueGeneral disorders | 7/38 | 3/48 | 5/41 | 5/38 | 10/78 |
| HeadacheNervous system disorders | 3/38 | 5/48 | 7/41 | 4/38 | 8/78 |
| Upper Respiratory Tract InfectionInfections and infestations | 0/38 | 0/48 | 0/41 | 0/38 | 10/78 |
| InsomniaPsychiatric disorders | 0/38 | 0/48 | 0/41 | 0/38 | 10/78 |
| NauseaGastrointestinal disorders | 4/38 | 3/48 | 4/41 | 1/38 | 4/78 |
| RashSkin and subcutaneous tissue disorders | 0/38 | 0/48 | 0/41 | 0/38 | 8/78 |
| Abdominal distensionGastrointestinal disorders | 2/38 | 0/48 | 4/41 | 1/38 | 6/78 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 0/38 | 1/48 | 4/41 | 0/38 | 5/78 |
| EpistaxisRespiratory, thoracic and mediastinal disorders | 0/38 | 0/48 | 4/41 | 0/38 | 0/78 |
| Age, Continuous(years) | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo | Total |
|---|---|---|---|---|---|
| Mean | 55.6 ± 9.3 | 55.9 ± 8.0 | 54.0 ± 9.7 | 54.8 ± 8.5 | 55.1 ± 8.8 |
| Sex: Female, Male(Participants) | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo | Total |
|---|---|---|---|---|---|
| Female | 38 | 45 | 38 | 36 | 157 |
| Male | 0 | 3 | 3 | 2 | 8 |
| Race/Ethnicity, Customized(participants) | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo | Total |
|---|---|---|---|---|---|
| White | 37 | 47 | 40 | 34 | 158 |
| Black | 0 | 0 | 1 | 1 | 2 |
| Asian | 1 | 0 | 0 | 1 | 2 |
| Other | 0 | 1 | 0 | 2 | 3 |
| Region of Enrollment(participants) | Obeticholic Acid (OCA) 10 Milligrams (mg) | OCA 25 mg | OCA 50 mg | Placebo | Total |
|---|---|---|---|---|---|
| France | 1 | 1 | 0 | 0 | 2 |
| United States | 15 | 21 | 19 | 17 | 72 |
| Canada | 13 | 15 | 14 | 13 | 55 |
| Spain | 1 | 2 | 1 | 2 | 6 |
| Austria | 1 | 2 | 2 | 1 | 6 |
| Germany | 2 | 3 | 2 | 1 | 8 |
| Netherlands | 1 | 1 | 1 | 1 | 4 |
| United Kingdom | 4 | 3 | 2 | 3 | 12 |
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Intercept Pharmaceuticals