Phase 4 Study of Obeticholic Acid Evaluating Clinical Outcomes in Patients With Primary Biliary Cholangitis (COBALT)

• ClinicalTrials.gov Identifier: NCT02308111
• Recruitment Status: Terminated
• First Posted: December 4, 2014
• Results First Posted: March 9, 2023
• Last Update Posted: March 9, 2023
• Sponsor: Intercept Pharmaceuticals
• Information provided by (Responsible Party): Intercept Pharmaceuticals

Study Description

Brief Summary:

Primary Biliary Cholangitis (PBC) is a serious, life-threatening, bile acid related liver disease of unknown cause. Without treatment, it frequently progresses to liver fibrosis and eventual cirrhosis requiring liver transplantation or resulting in death. The investigational drug, Obeticholic Acid (OCA) is a modified bile acid and FXR agonist that is derived from the primary human bile acid chenodeoxycholic acid. The key mechanisms of action of OCA, including its choleretic, anti-inflammatory, and anti-fibrotic properties, underlie its hepatoprotective effects and result in attenuation of injury and improved liver function in a cholestatic liver disease such as PBC. The study will assess the effect of OCA compared to placebo, combined with stable standard care, on clinical outcomes in PBC participants.

Condition or disease	Intervention/treatment	Phase
Liver Cirrhosis, Biliary	Drug: Obeticholic Acid (OCA); Drug: Placebo	Phase 4

Detailed Description:

This Phase 4, double-blind, randomized, placebo-controlled, multicenter study is being undertaken at up to 170 sites internationally to evaluate the effect of OCA on clinical outcomes in 428 participants with PBC. The study will include a screening period of up to 8 weeks, requiring two clinic visits. Eligible participants will be randomly allocated (1:1) to treatment with either OCA 5 mg or matching placebo tablets, taken orally once daily for the majority of participants; dose and frequency will be modified for participants with cirrhosis and classified as Child-Pugh (CP) B or C. Randomization will be stratified by standard treatment with UDCA (yes/no) and baseline liver function. The treatment period involves clinic visits approximately every 3 months. At the 3 month visit or any study visit thereafter, if study treatment is tolerated, participants' dose should be titrated per protocol in a blinded manner eg for participants who are non-cirrhotic or classified as CP A and randomized to OCA, they should receive the maximum daily dose of 10 mg OCA, those on placebo continue to receive placebo. Subsequently, daily dosage may return to 5 mg if necessary for these participants who are non-cirrhotic or classified as CP A, but should be increased to 10 mg if possible, based on tolerability and clinical judgment. Safety and tolerability will be assessed by monitoring adverse events and vital signs, and blood and urine testing. The study is event driven and total duration will be determined by the time required to accrue approximately 127 primary endpoint events, estimated to be approximately 10 years. Participants are expected to have a minimum follow-up time of approximately 6 years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 334 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 4, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Effect of Obeticholic Acid on Clinical Outcomes in Patients With Primary Biliary Cholangitis
• Actual Study Start Date: December 26, 2014
• Actual Primary Completion Date: December 23, 2021
• Actual Study Completion Date: December 23, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Obeticholic Acid (OCA) 5 mg to 10 mg; Obeticholic Acid (OCA) 5 mg for a minimum 3 months and then titrating up to a maximum 10 mg for the remainder of the trial (based on tolerability and CP Score).	Drug: Obeticholic Acid (OCA); Non-cirrhotic and classified as CP Class A: 5 mg tablet of OCA once daily titrating up to a maximum of 10 mg OCA once daily based on tolerability at 3 months for the duration of the study (majority of participants). Cirrhotic and classified as CP Class B and C: 5 mg tablet of OCA once weekly for at least 3 months, subsequently titrating up to a maximum dose and frequency of 10 mg OCA twice weekly based on tolerability and biochemical response for the duration of the study.; Other Names: 6alpha-ethylchenodeoxycholic acid (6-ECDCA); INT-747
Placebo Comparator: Placebo	Drug: Placebo; One tablet daily (or a lower frequency depending on CP score) for the remainder of the study

Outcome Measures

Primary Outcome Measures :

1. Time to the First Occurrence of Composite Endpoint [ Time Frame: Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years) ]
   To assess the effect of OCA, compared to placebo in conjunction with the established local standard of care, on clinical outcomes in participants with PBC as measured by time to the first occurrence of any of the following adjudicated events, derived as a composite event endpoint of death, liver transplant, model of end-stage liver disease (MELD) ≥15, uncontrolled ascites, or hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy (as defined by a West Haven score of >=2), or spontaneous bacterial peritonitis. The clinical events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% confidence intervals (CIs) for the clinical events distribution percentiles (25th and 50th) are provided.
2. Time to the First Occurrence of Primary Clinical Event (Expanded Endpoint) [ Time Frame: Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years) ]
   Primary clinical outcome event is the first occurrence of the following events: death, liver transplant, MELD score >=15 (MELD-Na score >=12 baseline), MELD-Na score >=15 (MELD-Na score <12 baseline), hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis), or bacterial empyema, uncontrolled or refractory ascites (requiring large volume paracentesis), portal hypertension syndromes, progression to decompensated liver disease, and progression to clinical evidence of portal hypertension without decompensation (for participants without decompensation or clinical evidence of portal hypertension at baseline). 71 endpoint events were observed in the OCA arm, and 80 were observed in the Placebo arm. The clinical events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the clinical events distribution percentiles (25th and 50th) are provided.

Secondary Outcome Measures :

1. Time To First Occurrence Of Severe Decompensating Events of Expanded Composite Endpoint [ Time Frame: Time to first occurrence from date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to 7 years) ]
   The first occurrence of the key secondary clinical event refers to the first occurrence of the following events: death, liver transplant, MELD-Na score >=15 if MELD-Na< 12 at baseline, MELD score >=15 if MELD-Na >=12 at baseline, uncontrolled or refractory ascites, portal hypertension syndromes (hepatorenal syndrome, portopulmonary syndrome, hepatopulmonary syndrome) or hospitalization for new onset or recurrence of variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis, or bacterial empyema. The clinical events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the clinical events distribution percentiles (25th and 50th) are provided.
2. Time To Liver Transplant Or Death (All-cause) [ Time Frame: Time to first occurrence from date of randomization until the date of first documented liver transplant or date of death from any cause (up to 7 years) ]
   The effect of OCA compared to placebo on time to liver transplant or death (all-cause) was assessed. The events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the clinical events distribution percentiles (25th and 50th) are provided.
3. Time to First Occurrence of Fatal Event (All-Cause) [ Time Frame: Time to first occurrence from date of randomization until the date of death from any cause (up to 7 years) ]
   The results represent the ratio of OCA to placebo. The fatal events distribution was estimated using the Kaplan-Meier methodology. Point estimates and 95% CIs for the fatal events distribution percentiles (25th and 50th) are provided
4. Time to First Occurrence of Liver Transplant [ Time Frame: Time to first occurrence from date of randomization until the date of first documented liver transplant or date of death from any cause (up to 5 years) ]
   The effect of OCA compared to placebo on time to occurrence of a liver transplant was assessed. The results represented the ratio of OCA to placebo. A hazard ratio <1 indicated an advantage for OCA. The event of interest was summarized through Cumulative Incidence Function (CIF) estimate at 5 years.
5. Time to First Occurrence of Hospitalization Due to Hepatic Events [ Time Frame: Time to first occurrence from date of randomization until the date of hospitalization, liver transplant or death from any cause, whichever came first (up to 5 years) ]
   Hospitalization events include new onset or recurrent variceal bleed, hepatic encephalopathy (as defined by a West Haven score of >=2), spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis OR presence of >250/mm^3 polymorph leucocytes [PMNs] in the ascitic fluid), bacterial empyema is confirmed by diagnostic thoracentesis OR presence of >250/mm^3 PMNs in the pleural fluid. The event of interest was summarized through CIF estimate at 5 years.
6. Time to First Occurrence of Uncontrolled or Refractory Ascites [ Time Frame: Time to first occurrence from date of randomization until the date of first documented uncontrolled or refractory ascites, liver transplant or date of death from any cause, whichever came first (up to 5 years) ]
   Uncontrolled or refractory ascites are defined as diuretic-resistant ascites requiring large-volume paracentesis. The effect of OCA compared to placebo on time to the first occurrence of uncontrolled or refractory ascites was assessed. The event of interest was summarized through CIF estimate at 5 years.
7. Time to First Occurrence of MELD Score ≥15 [ Time Frame: Time to first occurrence from date of randomization until the date of first documented MELD Score ≥15, liver transplant or date of death from any cause, whichever came first (up to 5 years) ]
   The MELD score is useful in assessing participants with significant decompensation. The MELD score is now used by the United Network for Organ Sharing in the United States and Eurotransplants to manage organ allocation for liver transplantation. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and International Normalized Ratio (INR), as appropriate, to predict survival. The MELD score ranges from 6 to 40. The higher the score, the more likely a participant will receive a liver from a deceased donor when an organ becomes available. The event of interest was summarized through CIF estimate at 5 years.
8. Time To Development Of Varix/Varices [ Time Frame: Time to first occurrence from date of randomization until the date of first documented development of varix/varices, liver transplant or death from any cause, whichever came first (up to 5 years) ]
   The effect of OCA compared to placebo on time to development of varix/varices was assessed. The event of interest was summarized through CIF estimate at 5 years.
9. Time To Liver-Related Death [ Time Frame: Time to first occurrence from date of randomization until the date of first liver-related or non-liver- related death, whichever came first (up to 5 years) ]
   The effect of OCA compared to placebo on time to liver-related death was assessed. The event of interest was summarized through CIF estimate at 5 years.
10. Time To Liver-Related Death Or Liver Transplant [ Time Frame: Time to first occurrence from date of randomization until the date of liver transplant, liver-related death or non-liver-related death from any cause, whichever came first (up to 5 years) ]
    The effect of OCA compared to placebo on time to liver-related death or liver transplant was assessed. The event of interest was summarized through CIF estimate at 5 years.
11. Time To Liver-Related Death, Liver Transplant, Or MELD Score ≥15 [ Time Frame: Time to first occurrence from date of randomization until the date of liver transplant, liver-related death, non-liver-related death from any cause or MELD Score ≥15, whichever came first (up to 5 years) ]
    The effect of OCA compared to placebo on time to liver-related death, liver transplant, or MELD Score ≥15 was assessed. The MELD score is useful in assessing participants with significant decompensation. The MELD score is now used by the United Network for Organ Sharing in the United States and Eurotransplants to manage organ allocation for liver transplantation. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and INR, as appropriate, to predict survival. The MELD score ranges from 6 to 40. The higher the score, the more likely a participant will receive a liver from a deceased donor when an organ becomes available. The event of interest was summarized through CIF estimate at 5 years.
12. Progression To Cirrhosis (for Noncirrhotic Subjects at Baseline) [ Time Frame: Time to first occurrence from date of randomization until the date of cirrhosis, liver transplant or death from any cause, whichever came first (up to 5 years) ]
    When a participant is identified as noncirrhotic at the Baseline and exhibited any signs or symptoms associated with progression to cirrhosis, the participant was assessed by Fibroscan® TE where available. The event of interest was summarized through CIF estimate at 5 years.
13. Time To Occurrence Of Hepatocellular Carcinoma (HCC) [ Time Frame: Time to first occurrence from date of randomization until the date of HCC diagnosis, liver transplant or death from any cause, whichever came first (up to 5 years) ]
    The effect of OCA compared to placebo on time to occurrence of HCC was assessed. The event of interest was summarized through CIF estimate at 5 years.
14. Change From Baseline To Month 24 Of Total Bilirubin [ Time Frame: Baseline up to Month 24 ]
    Liver biochemistry, which includes total bilirubin, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using mixed model repeated measures (MMRM), including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
15. Change From Baseline To Month 24 Of Direct Bilirubin [ Time Frame: Baseline up to Month 24 ]
    Liver biochemistry, which includes direct bilirubin, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
16. Change From Baseline To Month 24 Of Aspartate Aminotransferase (AST) [ Time Frame: Baseline up to Month 24 ]
    Liver biochemistry, which includes AST, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
17. Change From Baseline To Month 24 Of Alanine Aminotransferase (ALT) [ Time Frame: Baseline up to Month 24 ]
    Liver biochemistry, which includes ALT, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
18. Change From Baseline To Month 24 Of Alkaline Phosphatase (ALP) [ Time Frame: Baseline up to Month 24 ]
    Liver biochemistry, which includes ALP, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
19. Change From Baseline To Month 24 Of Gamma-glutamyl Transferase (GGT) [ Time Frame: Baseline up to Month 24 ]
    Liver biochemistry, which includes GGT, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
20. Change From Baseline To Month 24 Of Albumin [ Time Frame: Baseline up to Month 24 ]
    Liver biochemistry, which includes albumin, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
21. Change From Baseline To Month 24 Of INR [ Time Frame: Baseline up to Month 24 ]
    The coagulation test, which includes INR, was assessed to evaluate biochemical triggers that would prompt an immediate reevaluation of participants for potential hepatic injury or hepatic decompensation. INR is the ratio of tested prothrombin time to normal prothrombin time, to a power designated the international sensitivity index (ISI). INR normal range is 0.8 to 1.2 (female and male). Analysis was performed using MMRM, including treatment group, time, treatment group by time interaction, and randomization stratification factors as entered in the IWRS as fixed effects and baseline values as a covariate.
22. Change From Baseline To Month 72 Of MELD Score [ Time Frame: Baseline up to Month 72 ]
    The MELD score is useful in assessing participants with significant decompensation. The MELD score is now used by the United Network for Organ Sharing in the United States and Eurotransplants to manage organ allocation for liver transplantation. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and INR, as appropriate, to predict survival. The MELD score ranges from 6 to 40. The higher the score, the more likely a participant will receive a liver from a deceased donor when an organ becomes available.
23. Change From Baseline To Month 72 Of MELD-Na Score [ Time Frame: Baseline up to Month 72 ]
    The MELD-Na score is another useful predictor in assessing participants with significant decompensation. The MELD-Na took into account the effect of serum sodium as a reflection of renal function and hypothetically may improve the accuracy of the model score. The MELD-Na score is derived from the participant's serum total bilirubin, serum creatinine, INR, and serum sodium, as appropriate, to predict survival. The MELD-Na score ranges from 6 to 40. The higher the score, the more likely a participant will receive a liver from a deceased donor when an organ becomes available.
24. Change From Baseline To Month 72 Of CPS [ Time Frame: Baseline up to Month 72 ]
    Child-Pugh Score (Pugh 1973, Lucey 1997) was calculated and reported within the electronic data capture (EDC) system based on data entered into the CRF by adding the scores from the 5 factors and could have ranged from 5 to15. A total score of 5 to 6 was considered Grade A (mild, well-compensated disease); 7 to 9 was Grade B (moderate, significant functional compromise); and 10 and above was Grade C (severe, decompensated disease).
25. Change From Baseline To Month 72 Of Mayo Risk Score (MRS) [ Time Frame: Baseline up to Month 72 ]
    Mayo Risk Score (MRS) was calculated and reported within the EDC system. Calculation of MRS included Investigator assessment of peripheral edema and the use of diuretic therapy, which was assessed during the adverse event and concomitant medicine review at the scheduled visits and entered into the CRF, as well as total bilirubin, albumin, and prothrombin time results obtained from the central laboratory data. There is no maximum and minimum range of score but an increase in the MRS represents an increase in the risk of death.
26. Change From Baseline To Month 72 Of Immunoglobulin-M (IgM) [ Time Frame: Baseline up to Month 72 ]
    Markers of inflammation, which include IgM, were assessed.
27. Change From Baseline To Month 72 Of C-reactive Protein (CRP) [ Time Frame: Baseline up to Month 72 ]
    Markers of inflammation, which include CRP, were assessed.
28. Change From Baseline To Month 72 Of Tumor Necrosis Factor-α (TNF-α) [ Time Frame: Baseline up to Month 72 ]
    Markers of inflammation, which include TNF-α, were assessed.
29. Change From Baseline To Month 72 Of Fibroblast Growth Factor-19 (FGF-19) [ Time Frame: Baseline up to Month 72 ]
    Markers of hepatic fibrosis, which include FGF-19, were assessed.
30. Change From Baseline To Month 72 Of Cytokeratin-18 (CK-18) [ Time Frame: Baseline up to Month 72 ]
    Markers of inflammation, which include CK-18, were assessed.
31. Change From Baseline To Month 72 Of 7α-hydroxy-4-cholesten-3-one (C4) [ Time Frame: Baseline up to Month 72 ]
    Markers of hepatic fibrosis, which include C4, were assessed.
32. Change From Baseline To Month 72 Of Enhanced Liver Fibrosis (ELF) [ Time Frame: Baseline up to Month 72 ]
    Liver fibrosis was assessed using ELF test. The ELF test assessed: hyaluronic acid, procollagen3 N-terminal peptide, and a tissue inhibitor of metalloproteinase 1. The ELF test is a composite score: < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline suggests decreased fibrosis.
33. Change From Baseline To Month 72 Of Liver Stiffness - Transient Elastography [ Time Frame: Baseline up to Month 72 ]
    Hepatic stiffness was measured using non-invasive transient Elastography with Fibroscan® TE device.
34. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to the last IP dose plus 30 days and prior to commercial OCA initiation date (up to 7 years) ]
    An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as AEs that occurred on or after the date and time of study drug administration, or those that first occurred before dosing but worsened in frequency or severity after study drug administration. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
35. Pharmacokinetic (PK) Population: Fasting Trough Concentrations Of OCA By Dose Regimen [ Time Frame: Months 3, 6, 9, 12, 24, 36, 48, and 60 ]
    The fasting trough PK concentrations of OCA of different dose regimens taken throughout the study are reported.
36. PK Population: Serial Concentration of OCA By Dose Regimen [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4h, 5 h, and 6 h and PK serial concentrations at different dose regimen are reported.
37. PK Population: Area Under The Concentration-Time Curve (AUC) From 0 to 6 Hours Post-dose (AUC0-6h) Of Participants Who Received 5 mg QD OCA and With CP Score=Non-Cirrhotic (NC) [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose, 0.5h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4h, 5 h, and 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
38. PK Population: AUC From 0 to 24 Hours Post-dose (AUC0-24h) Of Participants Who Received 5 mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose, 0.5h, 0.75 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4h, 5 h, and 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
39. PK Population: Maximum Observed Concentration (Cmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
40. PK Population: Time to Cmax (Tmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
41. PK Population: Metabolite to Parent Ratio of AUC0-6h (MRAUC) Of Participants Who Received 5mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
42. PK Population: Metabolite to Parent Ratio of Cmax (MRCmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=NC.
43. PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
44. PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
45. PK Population: Cmax Of Participants Who Received 5mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
46. PK Population: Tmax Of Participants Who Received 5mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
47. PK Population: Concentration at 24 Hours Post-dose (Ctrough) Of Participants Who Received 5mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
48. PK Population: MRAUC Of Participants Who Received 5mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
49. PK Population: MRCmax Of Participants Who Received 5mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=A.
50. PK Population: Ctrough Of Participants Who Received 5mg QD OCA and With CP Score=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with CP Score=B.
51. PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
52. PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC
53. PK Population: Cmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
54. PK Population: Tmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
55. PK Population: Ctrough Of Participants Who Received 5mg QOD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
56. PK Population: MRAUC Of Participants Who Received 5mg QOD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
57. PK Population: MRCmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with CP Score=NC.
58. PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
59. PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
60. PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
61. PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
62. PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
63. PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
64. PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QOD OCA with CP Score=NC.
65. PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
66. PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CPS Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
67. PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
68. PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CPS Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
69. PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
70. PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
71. PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with CP Score=A.
72. PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
73. PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
74. PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
75. PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
76. PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With CP Score=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
77. PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With CP Score=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B
78. PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with CP Score=B.
79. PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
80. PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
81. PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
82. PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
83. PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
84. PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
85. PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=A.
86. PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
87. PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
88. PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
89. PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
90. PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
91. PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
92. PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QD OCA with MELD Category=B.
93. PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
94. PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
95. PK Population: Cmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
96. PK Population: Tmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
97. PK Population: Ctrough Of Participants Who Received 5 mg QOD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
98. PK Population: MRAUC Of Participants Who Received 5 mg QOD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
99. PK Population: MRCmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A [ Time Frame: Month 9 ]
    In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 5 mg QOD OCA with MELD Category=A.
100. PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
101. PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
102. PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A
103. PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
104. PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
105. PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
106. PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=A.
107. PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
108. PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
109. PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
110. PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
111. PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
112. PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
113. PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg QD OCA with MELD Category=B.
114. PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
115. PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
116. PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
117. PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
118. PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
119. PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
120. PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B [ Time Frame: Month 9 ]
     In Month 9, blood samples were collected at predose to 6 h for PK analysis in participants who received 10 mg Q2W OCA with MELD Category=B.
121. PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QD OCA [ Time Frame: Months 3, 6, 12, 24, and 48 ]
     The trough concentration of OCA in the cirrhotic participants who received 5 mg QD OCA was reported.
122. PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QD OCA [ Time Frame: Months 3, 6, 9, 12, and 24 ]
     The trough concentration of OCA in the non-cirrhotic participants who received 5 mg QD OCA was reported.
123. PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QOD OCA [ Time Frame: Months 6, 12, and 24 ]
     The trough concentration of OCA in the cirrhotic participants who received 5 mg QOD OCA was reported.
124. PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QOD OCA [ Time Frame: Months 3, 6, and 12 ]
     The trough concentration of OCA in the non-cirrhotic participants who received 5 mg QOD OCA was reported.
125. PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QW OCA [ Time Frame: Months 6 and 12 ]
     The trough concentration of OCA in the cirrhotic participants who received 5 mg QW OCA was reported.
126. PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QW OCA [ Time Frame: Month 12 ]
     In Month 12, the trough concentration of OCA in the non-cirrhotic participants who received 5 QW QOD OCA was reported.
127. PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg Q2W OCA [ Time Frame: Months 6, 24, 36 and 48 ]
     The trough concentration of OCA in the cirrhotic participants who received 5 mg Q2W OCA was reported.
128. PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg Q2W OCA [ Time Frame: Months 3, 6, 12, 24, 36, and 48 ]
     The trough concentration of OCA in the non-cirrhotic participants who received 5 Q2W QOD OCA was reported.
129. PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QD OCA [ Time Frame: Months 6, 9, 12, 24, 36, and 60 ]
     The trough concentration of OCA in the cirrhotic participants who received 10 mg QD OCA was reported.
130. PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QD OCA [ Time Frame: Months 6, 9, 12, 24, and 36 ]
     The trough concentration of OCA in the non-cirrhotic participants who received 10 QD QOD OCA was reported.
131. PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QOD OCA [ Time Frame: Months 3, 6, 9, 12, 24, 36, 48, and 60 ]
132. PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QOD OCA [ Time Frame: Month 12 ]
     In Month 12, the trough concentration of OCA in the non-cirrhotic participants who received 10 mg QOD OCA was reported.
133. PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg Q2W OCA [ Time Frame: Month 6 ]
     In Month 6, the trough concentration of OCA in the cirrhotic participants who received 10 mg Q2W OCA was reported.
134. PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg Q2W OCA [ Time Frame: Month 6 ]
     In Month 6, the trough concentration of OCA in the non-cirrhotic participants who received 10 mg Q2W OCA was reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Definite or probable PBC diagnosis (consistent with American Association for the Study of Liver Diseases [AASLD] and the European Association for the Study of the Liver [EASL] practice guidelines; Lindor 2009; EASL 2009), as demonstrated by the presence of ≥2 of the following 3 diagnostic factors:

   • History of elevated Alkaline phosphatase levels for at least 6 months
   • Positive antimitochondrial antibody (AMA) titer or if AMA negative or in low titer (<1:80) PBC-specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
   • Liver biopsy consistent with PBC
2. A mean total bilirubin >ULN and ≤5x ULN and/or a mean ALP >3x ULN
3. Either is not taking UDCA (no UDCA dose in the past 3 months) or has been taking UDCA for at least 12 months with a stable dose for ≥3 months prior to Day 0

Exclusion Criteria:

1. History or presence of other concomitant liver diseases including:

   • Hepatitis C virus infection
   • Active Hepatitis B infection; however, subjects who have seroconverted (hepatitis B surface antigen and hepatitis B e antigen negative) may be included in this study after consultation with the medical monitor
   • Primary sclerosing cholangitis (PSC)
   • Alcoholic liver disease
   • Definite autoimmune liver disease or overlap hepatitis
   • Nonalcoholic steatohepatitis (NASH)
   • Gilbert's Syndrome

2. Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:

   • History of liver transplant, current placement on a liver transplant list, or current Model of End Stage Liver Disease (MELD) score >12. Subjects who are placed on a transplant list despite a relatively early disease stage (for example per regional guidelines) may be eligible as long as they do not meet any of the other exclusion criteria

   • Cirrhosis with complications, including history (within the past 12 months) or presence of:

     • Variceal bleed
     • Uncontrolled ascites
     • Encephalopathy
     • Spontaneous bacterial peritonitis
   • Known or suspected HCC
   • Prior transjugular intrahepatic portosystemic shunt procedure
   • Hepatorenal syndrome (type I or II) or screening (Visit 1 or 2) serum creatinine >2 mg/dL (178 μmol/L)
3. Mean total bilirubin >5x ULN
4. Subjects who have undergone gastric bypass procedures (gastric lap band is acceptable) or ileal resection or plan to undergo either of these procedures
5. Other medical conditions that may diminish life expectancy, including known cancers (except carcinomas in situ or other stable, relatively benign conditions)
6. If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
7. Known history of human immunodeficiency virus infection
8. Medical conditions that may cause nonhepatic increases in ALP (eg, Paget's disease or fractures within 3 months)
9. Other clinically significant medical conditions that are not well controlled or for which medication needs are anticipated to change during the study
10. History of alcohol abuse or other substance abuse within 1 year prior to Day 0
11. Participation in another investigational product, biologic, or medical device study within 30 days prior to Screening. Participation in a previous study of OCA is allowed with 3 months washout prior to enrollment in this study
12. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain
13. History of known or suspected clinically significant hypersensitivity to OCA or any of its components
14. UDCA naïve (unless contraindicated)

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Arizona

Phoenix, Arizona, United States, 85054

United States, California

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

Inland Empire Liver Foundation

Rialto, California, United States, 92377

University of California Davis, Davis Medical Center

Sacramento, California, United States, 95817

Stanford University

Stanford, California, United States, 94304

United States, Colorado

University of Colorado Denver and Hospital

Aurora, Colorado, United States, 80045

United States, Florida

UF Hepatology Research at CTRB

Gainesville, Florida, United States, 32610

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, United States, 33163

United States, Georgia

Piedmont Atlanta Hospital

Atlanta, Georgia, United States, 30309

Emory University Hospital

Atlanta, Georgia, United States, 30322

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States, 30060

United States, Illinois

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States, 60637

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

Indianapolis Gastroenterology Research Foundation

Indianapolis, Indiana, United States, 46237

United States, Kentucky

University of Louisville, Medical Dental Complex

Louisville, Kentucky, United States, 40202

United States, Louisiana

Tulane University Medical Center

New Orleans, Louisiana, United States, 70112

United States, Maryland

Mercy Medical Center

Baltimore, Maryland, United States, 21202

United States, Massachusetts

UMass Medical School

Worcester, Massachusetts, United States, 01655

United States, Michigan

Henry Ford Health System

Novi, Michigan, United States, 48377

United States, Minnesota

Minnesota Gastroenterology, P.A.

Saint Paul, Minnesota, United States, 55114

United States, Mississippi

Southern Therapy and Advanced Research (STAR)

Jackson, Mississippi, United States, 39216

United States, Missouri

Kansas City Research Institute

Kansas City, Missouri, United States, 64131

Saint Louis University Gastroenterology & Hepatology

Saint Louis, Missouri, United States, 63104

United States, New Jersey

Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States, 07503

United States, New York

Mount Sinai Beth Israel

New York, New York, United States, 10003

Weill Cornell Medical College

New York, New York, United States, 10021

University of Rochester Medical Center

Rochester, New York, United States, 14642

United States, Pennsylvania

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

Quality Medical Research, PLLC

Nashville, Tennessee, United States, 37211

United States, Texas

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, United States, 75203

Baylor University Medical Center

Dallas, Texas, United States, 75246

Texas Digestive Disease Consultants

Dallas, Texas, United States, 75246

UT Southwestern Medical Center

Dallas, Texas, United States, 75390

Brooke Army Medical Center

Fort Sam Houston, Texas, United States, 78234

Baylor Scott and White Research Institute

Fort Worth, Texas, United States, 76104

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, United States, 77030

UT Health The University of Texas Health Science Center at Houston

Houston, Texas, United States, 77030

American Research Corporation at Texas Liver Institute

San Antonio, Texas, United States, 78215

Texas Digestive Disease Consultants

Southlake, Texas, United States, 76092

United States, Utah

Clinical Research Centers of America

Murray, Utah, United States, 84123

United States, Virginia

McGuire DVAMC

Richmond, Virginia, United States, 23249

United States, Washington

Swedish Organ Transplant & Liver Center

Seattle, Washington, United States, 98104

Argentina

Centro De Hepatología

La Plata, Buenos Aires, Argentina, B1902AWL

Hospital Universitario Austral

Presidente Derqui, Buenos Aires, Argentina, 1629

Dim Clínica Privada

Ramos Mejía, Buenos Aires, Argentina, 1704

Hospital Privado Universitario de Cordoba S.A.

Córdoba, Cordoba, Argentina, X5016KEH

Hospital Provincial del Centenario

Rosario, Santa Fe, Argentina, S2002KDS

CIPREC - Centro de Investigacion y Prevencion Cardiovascular S.A.

Buenos Aires, Argentina, 1119

Hospital De Clinicas University Of Buenos Aires

Buenos Aires, Argentina, 1120

Centrol Integral de Gastroenterologia

Buenos Aires, Argentina, 1425

Hospital Italiano de Buenos Aires

Ciudad Autónoma de Buenos Aires, Argentina, 1181

Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo

Ciudad Autónoma de Buenos Aires, Argentina, 1264

Hospital Aleman

Ciudad Autónoma de Buenos Aires, Argentina, C1118AAT

Hospital Britanico De Buenos Aires

Ciudad Autónoma de Buenos Aires, Argentina, C1280AEB

Australia, New South Wales

AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia, 2050

Department of Gastroenterology & Hepatology, Nepean Hospital

Kingswood, New South Wales, Australia, 2747

Australia, Queensland

Gallipoli Medical Research Foundation

Brisbane, Queensland, Australia, 4120

Australia, South Australia

Department of Gastroenterology and Hepatology, Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Flinders Medical Centre

Adelaide, South Australia, Australia, 5042

Australia, Victoria

Box Hill Hospital

Box Hill, Victoria, Australia, 3128

St. Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia, 3065

Austin Hospital

Heidelberg, Victoria, Australia, 3084

Australia, Western Australia

Fiona Stanley Hospital, Gastroenterology Department

Murdoch, Western Australia, Australia, 6150

Austria

AKH, Medical University of Vienna

Vienna, Austria, 1090

Belgium

University Hospital Antwerp

Edegem, Antwerp, Belgium, 2650

Uz Leuven

Leuven, Vlaams-Brabant, Belgium, 3000

Cub Hôpital Erasme

Bruxelles, Belgium, 1070

University Hospital Ghent

Ghent, Belgium, 9000

Brazil

Hospital Sao Rafael

São Salvador, Bahia, Brazil, 41253-190

Gastrocentro/ Universidade Estadual de Campinas (UNICAMP)

Sao Paulo, Campinas, Brazil, 13083-878

Instituto Hospital de Base do Distrito Federal-IHBDF

Brasilia, Distrito Federal Brazil, Brazil, 70335-900

Instituto Goiano de Gastroenterologia

Goiânia, Goias, Brazil, 74535-170

Cepec Huufma

Sao Luis, Maranhao, Brazil, 65020-600

Hospital das Clinicas da Universidade Federal de Minas Gerais (UFMG)

Belo Horizonte,, Minas Gerais, Brazil, 30130-100

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903

Hospital Universitario Professor Edgard Santos

Bahia, Salvador, Brazil, 40110-060

Gastrocentro. Unidad Estadual de CAmpinas UNICAMP

Campinas, Sao Paulo, Brazil, 13083-878

Universidade Federal do Estado do Rio de Janeiro - Hospital Universitario Gaffree e Guinle/HUGG/UNIRIO

Rio de Janeiro, Brazil, 20270-004

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP

Sao Paulo, Brazil, 05403-000

Bulgaria

St. Ivan Rilsky University Hospital

Sofia, Bulgaria, 1431

Canada, Alberta

University of Calgary Liver Unit (Heritage Medical Research Clinic)

Calgary, Alberta, Canada, T2N-4Z6

University of Alberta, Walter C. Mackenzie Health Sciences Centre (WMC)

Edmonton, Alberta, Canada, T6G 2X8

Canada, Manitoba

University Of Manitoba, Health Sciences Centre

Winnipeg, Manitoba, Canada, R3E 3P6

Canada, Ontario

London Health Sciences Centre-University Hospital

London, Ontario, Canada, N6A 5A5

University Health Network, Toronto General Hospital

Toronto, Ontario, Canada, M5G 2C4

Canada, Quebec

Chum

Montreal, Quebec, Canada, H2X 3J4

Chile

Centro De Investigaciones Clínicas Viña Del Mar

Viña Del Mar, V Región, Chile, 2540488

Denmark

Aarhus University Hospital Department of Hepatology and Gastroenterology

Aarhus, Aarhus C, Denmark, 8000

Medicinsk klinik for mave, tarm-og leversygdomme

København Ø, Denmark, 2100

Odense University Hospital Afdeling for medicinske mave-tarmsygdomme S

Odense, Denmark, 5000

Estonia

East Tallinn Central Hospital Gastroenterology Center

Tallinn, Harju, Estonia, 10138

Tartu University Hospital

Tartu, Estonia, 51014

Finland

Helsinki University Central Hospital

Helsinki, Finland, 00290

Turku University Central Hospital, Gastroenterology Outpatient Clinic

Turku,, Finland, 20521

France

Hospital Saint-Antoine, A.P.-H.P.

Paris Cedex 12, Paris, France, 75571

CHRU Hôpital HURIEZ

Lille, France, 59037

Chu De Bordeaux - Hôpital Haut Lévêque

Pessac Cedex, France, 33604

Germany

Klinikum der Johann-Wolfgang Goethe, Universitaet Frankfurt am Main

Frankfurt am Main, Hessen, Germany, 60590

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie

Hannover, Lower Saxony, Germany, D-30625

Friedrich-Alexander-Uniersitat Erlangen

Erlangen, QLD, Germany, 91054

CHARITÉ, Campus Virchow Klinikum

Berlin, Germany, D-13353

Univeritatsklinikum Hamburg Eppendorf, Medizinische Klinik und Poliklinik

Hamburg, Germany, 20246

Universitaetsklinikum Heidelberg Medizinische Universitaetsklinik

Heidelberg, Germany, 69120

Universität Leipzig KöR, Medizinische Fakultät

Leipzig, Germany, 04103

University of Munich, LMU Klinikum Grosshadern

Munich, Germany, 81377

Hong Kong

Queen Mary Hospital

Hong Kong, Pokfulam, Hong Kong

Prince Of Wales Hospital

Hong Kong, Shatin, Hong Kong

Tuen Mun Hospital

Hong Kong, Tuen Mun, New Territories, Hong Kong

Alice Ho Miu Ling Nethersole Hospital

Hong Kong, Hong Kong

Humanity & Health Research Centre

Hong Kong, Hong Kong

Hungary

Békés Megyei Kozponti Korhaz - Dr. Rethy Pal Tagkorhaz

Bekescsaba, Hungary, H-5600

Szent János Hospital

Budapest, Hungary, H-1125

University Of Debrecen, Department Of Medicine, Division Of Gastroenterology

Debrecen, Hungary, 4032

Israel

Hadassah Hebrew University Medical Center

Jerusalem, Nazareth Elit, Israel, POB 12000, 91120

Soroka Medical Center

Beer Sheva, Israel, 84104

Rambam Health Care Campus

Haifa, Israel, 31096

Shaare Zedek Medical Center

Jerusalem, Israel, 91031 02

Rabin Medical Center

Petach Tikva, Israel, 49100

Sheba Medical Center

Ramat-Gan, Israel, 52656 01

Sourasky Tel-Aviv Medical Center

Tel-Aviv, Israel, 64239

Italy

Azienda Ospedaliero - Universitaria di Cagliari - Centro per lo Studio delle Malattie del Fegato

Monserrato, Cagliari, Italy, 09042

Università Politecnica delle Marche - Azienda Ospedaliero

Ancona, Italy, 71-60126

AOU Policlinico Sant' Orsola Malpighi

Bologna, Italy, 40138

Azienda Ospedaliero Universitaria Sant´ Orsola Malpighi

Bologna, Italy, 40138

Azienda Ospedaliero Universitaria Careggi Universita di Firenze

Florence, Italy, 50139

Azienda Socio-Sanitarla Territoriale (ASST) Santi Paolo e Carlo

Milano, Italy, 20142

AOU Ospedale Civile S. Agostino Estense - UO Medicina Metabolica

Modena, Italy, 41126

Azienda Socio Sanitaria Territoriale (ASST) di Monza

Monza, Italy, 20900

Azienda Ospedaliero - Universita di Padova

Padova, Italy, 35128

AOU Policlinico Paolo Giaccone - Di.Bi.M.I.S

Palermo, Italy, 90127

Policlinico Universitario Agostino Gemelli - Universita Cattolica del Sacro Cuore

Rome, Italy, 00168

Korea, Republic of

Inje University Busan Paik Hospital

Busan, Busanjin-gu, Korea, Republic of, 47392

Gangnam Severance Hospital

Seoul, Gangnam-gu, Korea, Republic of, 06273

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620

Seoul National University Hospital

Seoul, Jongno-Gu, Korea, Republic of, 03080

Pusan National University Hospital

Busan, Seo-gu, Korea, Republic of, 49241

Lithuania

Hospital of Lithuanian University of Health Sciences, Kauno klinikos

Kaunas, Lithuania, LT 50009

Vilnius University Hospital Santaros klinikos

Vilnius, Lithuania, LT-08661

Mexico

Medica Sur, S.A.B. de C.V.

Ciudad de mexico, Ciudad De Mexico,, Mexico, 14050

Departamento De Gastroenterologia. Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran

Mexico City, DF, Mexico, 14000

Consultorio Médico de la Dra Alma Laura Ladrón de Guevara Cetina

Mexico City, DF, Mexico, 6700

Netherlands

Radboud UMC

Nijmegen, Gelderland, Netherlands, 6525 GA

Vrije Universiteit Medisch Centrum (VUMC)

Amsterdam, Noord-Holland, Netherlands, 1081HV

Erasmus Mc

Rotterdam, Zuid Holland, Netherlands, 3015 CE

Amsterdam University Medical Centre (AMC)

Amsterdam, Netherlands, 1105 AZ

University Medical Center Utrecht

Utrecht, Netherlands, 3584CX

New Zealand

NZ Liver Transplant Unit, Auckland Hospital

Grafton, Auckland, New Zealand, 1023

Gastroenterology, Christchurch Hospital

Christchurch, Canterbury, New Zealand, 4710

Poland

Nzoz Vitamed

Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-078

Wojewodzki Szpital Specjalistyczny im. J. Gromkowskiego, Pierwszy Oddzial Chorob Zakaznych

Wroclaw, Lover Silesia, Poland, 51-149

Medical University of Warsaw Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie (SPCSK in Warsaw

Warsaw, Masovia, Poland, 02-097

Centrum Onkologii - Instytut im. Marii Skłodowskiej - Curie, Klinika Gastroenterologii Onkologicznej

Warsaw, Mazovia, Poland, 02-781

Oddział Gastr. I Hepat. Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibińskiego Sum

Katowice, Silesia, Poland, 40-752

Dep. Of Gastroenterology UM Lublin

Lublin, Poland, 20-094

Portugal

Centro Hospitalar Lisboa Norte, EPE - Hospital de Santa Maria

Lisbon, Portugal, 1649-035

Serbia

Clinic For Gastroenterology And Hepatology Clinical Center Of Serbia

Belgrade, Serbia, 11000

Clinical Hospital Centre Zvezdara

Belgrade, Serbia, 11000

Spain

Hospital Universitario Marqués De Valdecilla

Santander, Cantabria, Spain, 39008

Hospital Universitario Puerta De Hierro Majadahonda

Majadahonda, Madrid, Spain, 28222

Hospital Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Virgen De La Victoria University Hospital

Málaga, Spain, 29010

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

La Fe, Hospital ( Valence )

Valence, Spain, 46026

Sweden

Karolinska University Hospital

Stockholm, Huddinge, Sweden, 14186

Sahlgrenska Universitetssjukhuset

Gothenburg, Sweden, 413 45

Switzerland

Inselspital, University Of Bern, UVCM, DMLL

Bern, Switzerland, 3010

Kantonsspital St. Gallen, Clinic for Gastroeterologie and Hepatologie

St. Gallen, Switzerland, 9007

USZ, Klinik für Gastroenterologie und Hepatologie

Zurich, Switzerland, 8091

Turkey

Ankara University School of Medicine Gastroenterology Dept.

Ankara, Turkey, 6100

Ege University School of Medicine Gastroenterology Dept.

Izmir, Turkey, 35100

United Kingdom

University Hospitals Bristol NHS Foundation Trust

Bristol, Avon, United Kingdom, BS2 8HW

Plymouth Hospitals NHS Trust, Derriford Hospital

Plymouth, Devon, United Kingdom, PL6 8DH

Gartnavel General Hospital

Glasgow, Lanarkshire, United Kingdom, G12 0YN

Forth Valley Royal Hospital

Larbert, Scotland, United Kingdom, FK5 4WR

Institute of Cellular Medicine

Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE2 4HH

University Hospitals Birmingham NHS Foundation Trust

Birmingham, West Midlands, United Kingdom, B15 2GW

Cambrigde University Hospitals NHS Foundation Trust

Cambridge, United Kingdom, CB2 0QQ

The Royal Free Hospital

London, United Kingdom, NW3 2QG

Nottingham University Hospital Nhs Trust

Nottingham, United Kingdom, NG7 2UH

Sponsors and Collaborators

Intercept Pharmaceuticals

Investigators

• Study Director: Erik Ness, MD; Intercept Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Intercept Pharmaceuticals:

Study Protocol  [PDF] November 5, 2019

Statistical Analysis Plan  [PDF] March 30, 2022

More Information

Publications:

Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.

European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009 Aug;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. Epub 2009 Jun 6. No abstract available.

• Responsible Party: Intercept Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02308111
• Other Study ID Numbers: 747-302
• First Posted: December 4, 2014
• Results First Posted: March 9, 2023
• Last Update Posted: March 9, 2023
• Last Verified: February 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Intercept Pharmaceuticals:

Primary Biliary Cirrhosis; PBC; Cirrhosis; Liver

Additional relevant MeSH terms:

Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary; Fibrosis; Pathologic Processes; Liver Diseases; Digestive System Diseases; Bile Duct Diseases; Biliary Tract Diseases; Cholestasis, Intrahepatic; Cholestasis