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

Liver Cirrhosis, Biliary Clinical Trial

— COBALT  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02308111
• Other study ID #: 747-302
• Status: Terminated
• Phase: Phase 4
• Start date: December 26, 2014
• Est. completion date: December 23, 2021

Study information

• Verified date: February 2023
• Source: Intercept Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 334
• Est. completion date: December 23, 2021
• Est. primary completion date: December 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cholangitis
• Fibrosis
• Liver Cirrhosis
• Liver Cirrhosis, Biliary

Intervention

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.
• Placebo
One tablet daily (or a lower frequency depending on CP score) for the remainder of the study

Locations

Country	Name	City	State
Argentina	Centrol Integral de Gastroenterologia	Buenos Aires
Argentina	CIPREC - Centro de Investigacion y Prevencion Cardiovascular S.A.	Buenos Aires
Argentina	Hospital De Clinicas University Of Buenos Aires	Buenos Aires
Argentina	Hospital Aleman	Ciudad Autónoma de Buenos Aires
Argentina	Hospital Britanico De Buenos Aires	Ciudad Autónoma de Buenos Aires
Argentina	Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo	Ciudad Autónoma de Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autónoma de Buenos Aires
Argentina	Hospital Privado Universitario de Cordoba S.A.	Córdoba	Cordoba
Argentina	Centro De Hepatología	La Plata	Buenos Aires
Argentina	Hospital Universitario Austral	Presidente Derqui	Buenos Aires
Argentina	Dim Clínica Privada	Ramos Mejía	Buenos Aires
Argentina	Hospital Provincial del Centenario	Rosario	Santa Fe
Australia	Department of Gastroenterology and Hepatology, Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinders Medical Centre	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Gallipoli Medical Research Foundation	Brisbane	Queensland
Australia	AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	St. Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Department of Gastroenterology & Hepatology, Nepean Hospital	Kingswood	New South Wales
Australia	Fiona Stanley Hospital, Gastroenterology Department	Murdoch	Western Australia
Austria	AKH, Medical University of Vienna	Vienna
Belgium	Cub Hôpital Erasme	Bruxelles
Belgium	University Hospital Antwerp	Edegem	Antwerp
Belgium	University Hospital Ghent	Ghent
Belgium	Uz Leuven	Leuven	Vlaams-Brabant
Brazil	Hospital Universitario Professor Edgard Santos	Bahia	Salvador
Brazil	Hospital das Clinicas da Universidade Federal de Minas Gerais (UFMG)	Belo Horizonte,	Minas Gerais
Brazil	Instituto Hospital de Base do Distrito Federal-IHBDF	Brasilia	Distrito Federal Brazil
Brazil	Gastrocentro. Unidad Estadual de CAmpinas UNICAMP	Campinas	Sao Paulo
Brazil	Instituto Goiano de Gastroenterologia	Goiânia	Goias
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Universidade Federal do Estado do Rio de Janeiro - Hospital Universitario Gaffree e Guinle/HUGG/UNIRIO	Rio de Janeiro
Brazil	Cepec Huufma	Sao Luis	Maranhao
Brazil	Gastrocentro/ Universidade Estadual de Campinas (UNICAMP)	Sao Paulo	Campinas
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP	Sao Paulo
Brazil	Hospital Sao Rafael	São Salvador	Bahia
Bulgaria	St. Ivan Rilsky University Hospital	Sofia
Canada	University of Calgary Liver Unit (Heritage Medical Research Clinic)	Calgary	Alberta
Canada	University of Alberta, Walter C. Mackenzie Health Sciences Centre (WMC)	Edmonton	Alberta
Canada	London Health Sciences Centre-University Hospital	London	Ontario
Canada	Chum	Montreal	Quebec
Canada	University Health Network, Toronto General Hospital	Toronto	Ontario
Canada	University Of Manitoba, Health Sciences Centre	Winnipeg	Manitoba
Chile	Centro De Investigaciones Clínicas Viña Del Mar	Viña Del Mar	V Región
Denmark	Aarhus University Hospital Department of Hepatology and Gastroenterology	Aarhus	Aarhus C
Denmark	Medicinsk klinik for mave, tarm-og leversygdomme	København Ø
Denmark	Odense University Hospital Afdeling for medicinske mave-tarmsygdomme S	Odense
Estonia	East Tallinn Central Hospital Gastroenterology Center	Tallinn	Harju
Estonia	Tartu University Hospital	Tartu
Finland	Helsinki University Central Hospital	Helsinki
Finland	Turku University Central Hospital, Gastroenterology Outpatient Clinic	Turku,
France	CHRU Hôpital HURIEZ	Lille
France	Hospital Saint-Antoine, A.P.-H.P.	Paris Cedex 12	Paris
France	Chu De Bordeaux - Hôpital Haut Lévêque	Pessac Cedex
Germany	CHARITÉ, Campus Virchow Klinikum	Berlin
Germany	Friedrich-Alexander-Uniersitat Erlangen	Erlangen	QLD
Germany	Klinikum der Johann-Wolfgang Goethe, Universitaet Frankfurt am Main	Frankfurt am Main	Hessen
Germany	Univeritatsklinikum Hamburg Eppendorf, Medizinische Klinik und Poliklinik	Hamburg
Germany	Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie	Hannover	Lower Saxony
Germany	Universitaetsklinikum Heidelberg Medizinische Universitaetsklinik	Heidelberg
Germany	Universität Leipzig KöR, Medizinische Fakultät	Leipzig
Germany	University of Munich, LMU Klinikum Grosshadern	Munich
Hong Kong	Alice Ho Miu Ling Nethersole Hospital	Hong Kong
Hong Kong	Humanity & Health Research Centre	Hong Kong
Hong Kong	Prince Of Wales Hospital	Hong Kong	Shatin
Hong Kong	Queen Mary Hospital	Hong Kong	Pokfulam
Hong Kong	Tuen Mun Hospital	Hong Kong	Tuen Mun, New Territories
Hungary	Békés Megyei Kozponti Korhaz - Dr. Rethy Pal Tagkorhaz	Bekescsaba
Hungary	Szent János Hospital	Budapest
Hungary	University Of Debrecen, Department Of Medicine, Division Of Gastroenterology	Debrecen
Israel	Soroka Medical Center	Beer Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Hebrew University Medical Center	Jerusalem	Nazareth Elit
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Rabin Medical Center	Petach Tikva
Israel	Sheba Medical Center	Ramat-Gan
Israel	Sourasky Tel-Aviv Medical Center	Tel-Aviv
Italy	Università Politecnica delle Marche - Azienda Ospedaliero	Ancona
Italy	AOU Policlinico Sant' Orsola Malpighi	Bologna
Italy	Azienda Ospedaliero Universitaria Sant´ Orsola Malpighi	Bologna
Italy	Azienda Ospedaliero Universitaria Careggi Universita di Firenze	Florence
Italy	Azienda Socio-Sanitarla Territoriale (ASST) Santi Paolo e Carlo	Milano
Italy	AOU Ospedale Civile S. Agostino Estense - UO Medicina Metabolica	Modena
Italy	Azienda Ospedaliero - Universitaria di Cagliari - Centro per lo Studio delle Malattie del Fegato	Monserrato	Cagliari
Italy	Azienda Socio Sanitaria Territoriale (ASST) di Monza	Monza
Italy	Azienda Ospedaliero - Universita di Padova	Padova
Italy	AOU Policlinico Paolo Giaccone - Di.Bi.M.I.S	Palermo
Italy	Policlinico Universitario Agostino Gemelli - Universita Cattolica del Sacro Cuore	Rome
Korea, Republic of	Inje University Busan Paik Hospital	Busan	Busanjin-gu
Korea, Republic of	Pusan National University Hospital	Busan	Seo-gu
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Gangnam Severance Hospital	Seoul	Gangnam-gu
Korea, Republic of	Seoul National University Hospital	Seoul	Jongno-Gu
Lithuania	Hospital of Lithuanian University of Health Sciences, Kauno klinikos	Kaunas
Lithuania	Vilnius University Hospital Santaros klinikos	Vilnius
Mexico	Medica Sur, S.A.B. de C.V.	Ciudad de mexico	Ciudad De Mexico,
Mexico	Consultorio Médico de la Dra Alma Laura Ladrón de Guevara Cetina	Mexico City	DF
Mexico	Departamento De Gastroenterologia. Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran	Mexico City	DF
Netherlands	Amsterdam University Medical Centre (AMC)	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum (VUMC)	Amsterdam	Noord-Holland
Netherlands	Radboud UMC	Nijmegen	Gelderland
Netherlands	Erasmus Mc	Rotterdam	Zuid Holland
Netherlands	University Medical Center Utrecht	Utrecht
New Zealand	Gastroenterology, Christchurch Hospital	Christchurch	Canterbury
New Zealand	NZ Liver Transplant Unit, Auckland Hospital	Grafton	Auckland
Poland	Nzoz Vitamed	Bydgoszcz	Kujawsko-Pomorskie
Poland	Oddzial Gastr. I Hepat. Uniwersyteckie Centrum Kliniczne Im. Prof. K. Gibinskiego Sum	Katowice	Silesia
Poland	Dep. Of Gastroenterology UM Lublin	Lublin
Poland	Centrum Onkologii - Instytut im. Marii Sklodowskiej - Curie, Klinika Gastroenterologii Onkologicznej	Warsaw	Mazovia
Poland	Medical University of Warsaw Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie (SPCSK in Warsaw	Warsaw	Masovia
Poland	Wojewodzki Szpital Specjalistyczny im. J. Gromkowskiego, Pierwszy Oddzial Chorob Zakaznych	Wroclaw	Lover Silesia
Portugal	Centro Hospitalar Lisboa Norte, EPE - Hospital de Santa Maria	Lisbon
Serbia	Clinic For Gastroenterology And Hepatology Clinical Center Of Serbia	Belgrade
Serbia	Clinical Hospital Centre Zvezdara	Belgrade
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Puerta De Hierro Majadahonda	Majadahonda	Madrid
Spain	Virgen De La Victoria University Hospital	Málaga
Spain	Hospital Universitario Marqués De Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	La Fe, Hospital ( Valence )	Valence
Sweden	Sahlgrenska Universitetssjukhuset	Gothenburg
Sweden	Karolinska University Hospital	Stockholm	Huddinge
Switzerland	Inselspital, University Of Bern, UVCM, DMLL	Bern
Switzerland	Kantonsspital St. Gallen, Clinic for Gastroeterologie and Hepatologie	St. Gallen
Switzerland	USZ, Klinik für Gastroenterologie und Hepatologie	Zurich
Turkey	Ankara University School of Medicine Gastroenterology Dept.	Ankara
Turkey	Ege University School of Medicine Gastroenterology Dept.	Izmir
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham	West Midlands
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol	Avon
United Kingdom	Cambrigde University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Gartnavel General Hospital	Glasgow	Lanarkshire
United Kingdom	Forth Valley Royal Hospital	Larbert	Scotland
United Kingdom	The Royal Free Hospital	London
United Kingdom	Institute of Cellular Medicine	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Nottingham University Hospital Nhs Trust	Nottingham
United Kingdom	Plymouth Hospitals NHS Trust, Derriford Hospital	Plymouth	Devon
United States	Emory University Hospital	Atlanta	Georgia
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	University of Colorado Denver and Hospital	Aurora	Colorado
United States	Mercy Medical Center	Baltimore	Maryland
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Baylor University Medical Center	Dallas	Texas
United States	Texas Digestive Disease Consultants	Dallas	Texas
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Baylor Scott and White Research Institute	Fort Worth	Texas
United States	UF Hepatology Research at CTRB	Gainesville	Florida
United States	Baylor College of Medicine - Advanced Liver Therapies	Houston	Texas
United States	UT Health The University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Indianapolis Gastroenterology Research Foundation	Indianapolis	Indiana
United States	Southern Therapy and Advanced Research (STAR)	Jackson	Mississippi
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Louisville, Medical Dental Complex	Louisville	Kentucky
United States	Gastrointestinal Specialists of Georgia	Marietta	Georgia
United States	Schiff Center for Liver Diseases/University of Miami	Miami	Florida
United States	Clinical Research Centers of America	Murray	Utah
United States	Quality Medical Research, PLLC	Nashville	Tennessee
United States	Tulane University Medical Center	New Orleans	Louisiana
United States	Mount Sinai Beth Israel	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Henry Ford Health System	Novi	Michigan
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Inland Empire Liver Foundation	Rialto	California
United States	McGuire DVAMC	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California Davis, Davis Medical Center	Sacramento	California
United States	Saint Louis University Gastroenterology & Hepatology	Saint Louis	Missouri
United States	Minnesota Gastroenterology, P.A.	Saint Paul	Minnesota
United States	American Research Corporation at Texas Liver Institute	San Antonio	Texas
United States	Swedish Organ Transplant & Liver Center	Seattle	Washington
United States	Texas Digestive Disease Consultants	Southlake	Texas
United States	Stanford University	Stanford	California
United States	UMass Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Intercept Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Denmark,  Estonia,  Finland,  France,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Lithuania,  Mexico,  Netherlands,  New Zealand,  Poland,  Portugal,  Serbia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to the First Occurrence of Composite Endpoint	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.	Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years)
Primary	Time to the First Occurrence of Primary Clinical Event (Expanded Endpoint)	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.	Time to first occurrence from date of randomization until the time to accrue approximately 127 primary endpoint events (up to 7 years)
Secondary	Time To First Occurrence Of Severe Decompensating Events of Expanded Composite Endpoint	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.	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)
Secondary	Time To Liver Transplant Or Death (All-cause)	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.	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)
Secondary	Time to First Occurrence of Fatal Event (All-Cause)	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	Time to first occurrence from date of randomization until the date of death from any cause (up to 7 years)
Secondary	Time to First Occurrence of Liver Transplant	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.	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)
Secondary	Time to First Occurrence of Hospitalization Due to Hepatic Events	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.	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)
Secondary	Time to First Occurrence of Uncontrolled or Refractory Ascites	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.	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)
Secondary	Time to First Occurrence of MELD Score =15	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.	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)
Secondary	Time To Development Of Varix/Varices	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.	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)
Secondary	Time To Liver-Related Death	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.	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)
Secondary	Time To Liver-Related Death Or Liver Transplant	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.	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)
Secondary	Time To Liver-Related Death, Liver Transplant, Or MELD Score =15	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.	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)
Secondary	Progression To Cirrhosis (for Noncirrhotic Subjects at Baseline)	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.	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)
Secondary	Time To Occurrence Of Hepatocellular Carcinoma (HCC)	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.	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)
Secondary	Change From Baseline To Month 24 Of Total Bilirubin	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.	Baseline up to Month 24
Secondary	Change From Baseline To Month 24 Of Direct Bilirubin	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.	Baseline up to Month 24
Secondary	Change From Baseline To Month 24 Of Aspartate Aminotransferase (AST)	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.	Baseline up to Month 24
Secondary	Change From Baseline To Month 24 Of Alanine Aminotransferase (ALT)	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.	Baseline up to Month 24
Secondary	Change From Baseline To Month 24 Of Alkaline Phosphatase (ALP)	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.	Baseline up to Month 24
Secondary	Change From Baseline To Month 24 Of Gamma-glutamyl Transferase (GGT)	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.	Baseline up to Month 24
Secondary	Change From Baseline To Month 24 Of Albumin	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.	Baseline up to Month 24
Secondary	Change From Baseline To Month 24 Of INR	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.	Baseline up to Month 24
Secondary	Change From Baseline To Month 72 Of MELD Score	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.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of MELD-Na Score	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.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of CPS	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).	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of Mayo Risk Score (MRS)	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.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of Immunoglobulin-M (IgM)	Markers of inflammation, which include IgM, were assessed.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of C-reactive Protein (CRP)	Markers of inflammation, which include CRP, were assessed.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of Tumor Necrosis Factor-a (TNF-a)	Markers of inflammation, which include TNF-a, were assessed.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of Fibroblast Growth Factor-19 (FGF-19)	Markers of hepatic fibrosis, which include FGF-19, were assessed.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of Cytokeratin-18 (CK-18)	Markers of inflammation, which include CK-18, were assessed.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of 7a-hydroxy-4-cholesten-3-one (C4)	Markers of hepatic fibrosis, which include C4, were assessed.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of Enhanced Liver Fibrosis (ELF)	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.	Baseline up to Month 72
Secondary	Change From Baseline To Month 72 Of Liver Stiffness - Transient Elastography	Hepatic stiffness was measured using non-invasive transient Elastography with Fibroscan® TE device.	Baseline up to Month 72
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	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.	Baseline up to the last IP dose plus 30 days and prior to commercial OCA initiation date (up to 7 years)
Secondary	Pharmacokinetic (PK) Population: Fasting Trough Concentrations Of OCA By Dose Regimen	The fasting trough PK concentrations of OCA of different dose regimens taken throughout the study are reported.	Months 3, 6, 9, 12, 24, 36, 48, and 60
Secondary	PK Population: Serial Concentration of OCA By Dose Regimen	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.	Month 9
Secondary	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)	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.	Month 9
Secondary	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	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.	Month 9
Secondary	PK Population: Maximum Observed Concentration (Cmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: Time to Cmax (Tmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: Metabolite to Parent Ratio of AUC0-6h (MRAUC) Of Participants Who Received 5mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: Metabolite to Parent Ratio of Cmax (MRCmax) Of Participants Who Received 5mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 5mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 5mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: Concentration at 24 Hours Post-dose (Ctrough) Of Participants Who Received 5mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 5mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 5mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 5mg QD OCA and With CP Score=B	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With CP Score=NC	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	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 5mg QOD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 5mg QOD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 5mg QOD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=NC	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With CPS Score=A	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With CPS Score=A	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With CP Score=A	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With CP Score=B	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With CP Score=B	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With CP Score=B	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	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With CP Score=B	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 5 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 5 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 5 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 5 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 5 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 5 mg QOD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 5 mg QOD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 5 mg QOD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 5 mg QOD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A	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	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=A	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 10 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 10 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 10 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 10 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 10 mg QD OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: AUC0-6h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: AUC0-24h Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Cmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Tmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Ctrough Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: MRAUC Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: MRCmax Of Participants Who Received 10 mg Q2W OCA and With MELD Category=B	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.	Month 9
Secondary	PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QD OCA	The trough concentration of OCA in the cirrhotic participants who received 5 mg QD OCA was reported.	Months 3, 6, 12, 24, and 48
Secondary	PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QD OCA	The trough concentration of OCA in the non-cirrhotic participants who received 5 mg QD OCA was reported.	Months 3, 6, 9, 12, and 24
Secondary	PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QOD OCA	The trough concentration of OCA in the cirrhotic participants who received 5 mg QOD OCA was reported.	Months 6, 12, and 24
Secondary	PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QOD OCA	The trough concentration of OCA in the non-cirrhotic participants who received 5 mg QOD OCA was reported.	Months 3, 6, and 12
Secondary	PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg QW OCA	The trough concentration of OCA in the cirrhotic participants who received 5 mg QW OCA was reported.	Months 6 and 12
Secondary	PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg QW OCA	In Month 12, the trough concentration of OCA in the non-cirrhotic participants who received 5 QW QOD OCA was reported.	Month 12
Secondary	PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 5 mg Q2W OCA	The trough concentration of OCA in the cirrhotic participants who received 5 mg Q2W OCA was reported.	Months 6, 24, 36 and 48
Secondary	PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 5 mg Q2W OCA	The trough concentration of OCA in the non-cirrhotic participants who received 5 Q2W QOD OCA was reported.	Months 3, 6, 12, 24, 36, and 48
Secondary	PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QD OCA	The trough concentration of OCA in the cirrhotic participants who received 10 mg QD OCA was reported.	Months 6, 9, 12, 24, 36, and 60
Secondary	PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QD OCA	The trough concentration of OCA in the non-cirrhotic participants who received 10 QD QOD OCA was reported.	Months 6, 9, 12, 24, and 36
Secondary	PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg QOD OCA		Months 3, 6, 9, 12, 24, 36, 48, and 60
Secondary	PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg QOD OCA	In Month 12, the trough concentration of OCA in the non-cirrhotic participants who received 10 mg QOD OCA was reported.	Month 12
Secondary	PK Population: Trough Concentrations Of Cirrhotic Participants Who Received 10 mg Q2W OCA	In Month 6, the trough concentration of OCA in the cirrhotic participants who received 10 mg Q2W OCA was reported.	Month 6
Secondary	PK Population: Trough Concentrations Of Non-Cirrhotic Participants Who Received 10 mg Q2W OCA	In Month 6, the trough concentration of OCA in the non-cirrhotic participants who received 10 mg Q2W OCA was reported.	Month 6