Study of Obeticholic Acid (OCA) Evaluating Pharmacokinetics and Safety in Participants With Primary Biliary Cholangitis (PBC) and Hepatic Impairment

Liver Cirrhosis, Biliary Clinical Trial

Official title:

A Phase 4, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Pharmacokinetics and Safety of Obeticholic Acid in Patients With Primary Biliary Cholangitis and Moderate to Severe Hepatic Impairment

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03633227
• Other study ID #: 747-401
• Status: Terminated
• Phase: Phase 4
• Start date: June 22, 2018
• Est. completion date: July 9, 2021

Study information

• Verified date: August 2022
• Source: Intercept Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 4, randomized, double-blind, placebo-controlled study will evaluate the pharmacokinetics (PK) and safety of OCA treatment in participants with PBC and moderate to severe hepatic impairment over a 48-week treatment period. Participants who have completed their 48-week double blind treatment period will continue double-blind treatment until all randomized participants have completed their 48-week treatment period and the database for that period is locked. An open-label extension study in which all participants receive OCA will be considered following review of blinded safety and PK data.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: July 9, 2021
• Est. primary completion date: July 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. A definite or probable diagnosis of PBC (consistent with American Association for the Study of Liver Diseases [AASLD] and European Association for the Study of the Liver [EASL] Practice Guidelines, defined as having =2 of the following 3 diagnostic factors:

• History of elevated alkaline phosphatase (ALP) levels for at least 6 months

• Positive antimitochondrial antibody (AMA) titer or if AMA negative or low titer (=1:80), PBC specific antibodies (anti-glycoprotein 210 [GP210] and/or anti-SP100) and/or antibodies against the major M2 components (E2 component of mitochondrial pyruvate dehydrogenase complex [PDC-E2], 2-oxo-glutaric acid dehydrogenase complex)

• Liver biopsy consistent with PBC (collected at any time prior to Screening)

2. Evidence of cirrhosis including at least one of the following:

• Biopsy results consistent with PBC Stage 4

• Liver stiffness as assessed by Transient Elastography (TE) Median Value =16.9 kilopascals (kPa)

• Clinical evidence in the absence of acute liver failure consistent with cirrhosis including: gastroesophageal varices, ascites, radiological evidence of cirrhosis (nodular liver or enlargement of portal vein and splenomegaly)

• Combined low platelet count (<140,000/cubic millimeter [mm^3]) with

• persistent decrease in serum albumin, or

• elevation in prothrombin time/international normalized ratio (INR) (not due to antithrombotic agent use), or

• elevated bilirubin (2*upper limit of normal [ULN])

3. Satisfy the criteria of the modified Child-Pugh (CP) classification for hepatic impairment during Screening:

• Moderate: CP-B (Scores 7 to 9) or

• Severe: CP-C (Scores 10 to 12)

4. Model of end-stage liver disease (MELD) score of 6 to 24 at Screening

5. Taking ursodeoxycholic acid (UDCA) for at least 12 months (stable dose for =3 months) prior to Day 1, or unable to tolerate or unresponsive to UDCA (no UDCA for =3 months)

Exclusion Criteria:

1. Non-cirrhotic or cirrhotic CP-A (Mild; Score 5 to 6)

2. History of liver transplant or organ transplant

3. History of alcohol or drug abuse within 12 months prior to Screening

4. Hepatic encephalopathy (as defined by a West Haven score of =2

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

• Hepatitis C virus infection and ribonucleic acid (RNA) positive

• Active hepatitis B infection; however, participants 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

• Alcoholic liver disease

• Definite autoimmune liver disease or overlap hepatitis

• Gilbert's Syndrome

6. In the opinion of the Investigator, fluctuating or rapidly deteriorating hepatic function prior to randomization

Other inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Obeticholic Acid (OCA)
OCA will be administered per dose and schedule specified in the arm description.
• Placebo
OCA matching placebo will be administered per the schedule specified in the arm description.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Universitario Austral	Buenos Aires
Argentina	Hospital Aleman	Caba
Argentina	Hospital Britanico de Buenos Aires	Caba
Argentina	Hospital de Gastroenterologia "Dr Carlos Bonorino Udaondo"	Ciudad Autonoma de Buenos Aire
Argentina	Higea S.A.	Mendoza
Argentina	Hospital Universitario Austral	Pilar
Argentina	Hospital Provincial del Centenario	Rosario
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Nepean Hospital	Kingswood
Belgium	CUB Hospital Erasme	Brussels
Belgium	Universitair Ziekenhuis Antwerpen UZA	Edegem
Belgium	University Hospital Leuven	Leuven
Brazil	Hospital das Clínicas da Universidade Federal de Minas Gerais - UFMG	Belo Horizonte
Brazil	Hospital de Clinicas de Porto Alegre	Rio Grande
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo
Canada	Toronto General Hospital	Toronto
Estonia	West Tallinn Central Hospital	Tallinn
Estonia	Tartu University Hospital	Tartu
Germany	Universitatsklinikum Leipzig AoR	Leipzig
Hungary	Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaz, 4. Belgyogyaszat-Gasztroenterologia-Hepatologia	Bekescsaba
Italy	AOU Ospedale Civile S. Agostino Estense - UO Medicina Metabolica	Modena
Italy	Azienda Socio Sanitaria Territoriale (ASST) di Monza	Monza	MB
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno Klinikos	Kaunas
Lithuania	Klaipeda Seamen's Hospital	Klaipeda
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Spain	Paseo Vall d'Hebron	Barcelona
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitari I Politecnic La Fe de Valencia	Valencia
United States	University Of Michigan	Ann Arbor	Michigan
United States	Mercy Medical Center	Baltimore	Maryland
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	Baylor College of Medicine- Advanced Liver Therapies	Houston	Texas
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Schiff Center for Liver Diseases/ University of Miami	Miami	Florida
United States	UPMC Center for Liver Diseases	Pittsburgh	Pennsylvania
United States	Inland Empire Liver Foundation	Rialto	California
United States	University of California, Ddavis Medical Center	Sacramento	California
United States	American Research Corporation at theTexas Liver Institute	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Intercept Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Estonia,  Germany,  Hungary,  Italy,  Lithuania,  Spain, 

References & Publications (3)

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. — 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. — View Citation

Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug;60(2):715-35. doi: 10.1002/hep.27210. Epub 2014 Jul 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Concentration (Cmax) of Total OCA at Week 12	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. Pharmacokinetics (PK) of OCA 5 mg twice weekly or 10 mg twice weekly at Week 12 are not applicable as no participant started 5 mg twice weekly or 10 mg twice weekly at Week 12.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Time to Maximum Concentration (Tmax) of Total OCA at Week 12	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Trough Concentration (Ctrough) of Total OCA at Week 12	Ctrough was considered as the concentration at 24-hours post-dose at Week 12. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	24 hours post-dose at Week 12
Primary	Area Under the Concentration Versus Time Curve From Zero Time to 24 Hours (AUC0-24h) of Total OCA at Week 12	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Cmax of Total OCA at Week 18	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Tmax of Total OCA at Week 18	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Ctrough of Total OCA at Week 18	Ctrough was considered as the concentration at 24-hours post-dose at Week 18. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	24 hours post-dose at Week 18
Primary	AUC0-24h of Total OCA at Week 18	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Cmax of Total OCA at Week 24	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Tmax of Total OCA at Week 24	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Ctrough of Total OCA at Week 24	Ctrough was considered as the concentration at 24-hours post-dose at Week 24. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	24 hours post-dose at Week 24
Primary	AUC0-24h of Total OCA at Week 24	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Cmax of Total OCA at Week 30	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Tmax of Total OCA at Week 30	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Ctrough of Total OCA at Week 30	Ctrough was considered as the concentration at 24-hours post-dose at Week 30. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	24 hours post-dose at Week 30
Primary	AUC0-24h of Total OCA at Week 30	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Cmax of Total OCA at Week 48	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Tmax of Total OCA at Week 48	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Ctrough of Total OCA at Week 48	Ctrough was considered as the concentration at 24-hours post-dose at Week 48. Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA.	24 hours post-dose at Week 48
Primary	AUC0-24h of Total OCA at Week 48	Total OCA is molar sum of unconjugated OCA, glyco-OCA, and tauro-OCA. AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Cmax of Unconjugated OCA at Week 12		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Tmax of Unconjugated OCA at Week 12		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Ctrough of Unconjugated OCA at Week 12	Ctrough was considered as the concentration at 24-hours post-dose at Week 12.	24 hours post-dose at Week 12
Primary	AUC0-24h of Unconjugated OCA at Week 12	AUC0-24 was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Cmax of Unconjugated OCA at Week 18		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Tmax of Unconjugated OCA at Week 18		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Ctrough of Unconjugated OCA at Week 18	Ctrough was considered as the concentration at 24-hours post-dose at Week 18.	24 hours post-dose at Week 18
Primary	AUC0-24h of Unconjugated OCA at Week 18	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Cmax of Unconjugated OCA at Week 24		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Tmax of Unconjugated OCA at Week 24		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Ctrough of Unconjugated OCA at Week 24	Ctrough was considered as the concentration at 24-hours post-dose at Week 24.	24 hours post-dose at Week 24
Primary	AUC0-24h of Unconjugated OCA at Week 24	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Cmax of Unconjugated OCA at Week 30		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Tmax of Unconjugated OCA at Week 30		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Ctrough of Unconjugated OCA at Week 30	Ctrough was considered as the concentration at 24-hours post-dose at Week 30.	24 hours post-dose at Week 30
Primary	AUC0-24h of Unconjugated OCA at Week 30	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Cmax of Unconjugated OCA at Week 48		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Tmax of Unconjugated OCA at Week 48		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Ctrough of Unconjugated OCA at Week 48	Ctrough was considered as the concentration at 24-hours post-dose at Week 48.	24 hours post-dose at Week 48
Primary	AUC0-24h of Unconjugated OCA at Week 48	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Cmax of Glyco Conjugate of OCA (Glyco-OCA) at Week 12		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Tmax of Glyco-OCA at Week 12		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Ctrough of Glyco-OCA at Week 12	Ctrough was considered as the concentration at 24-hours post-dose at Week 12.	24 hours post-dose at Week 12
Primary	AUC0-24h of Glyco-OCA at Week 12	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Metabolite to Parent Ratio of AUC-0-24h (MRAUC) of Glyco-OCA at Week 12	MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Metabolite to Parent Ratio of Cmax (MRCmax) of Glyco-OCA at Week 12	MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Cmax of Glyco-OCA at Week 18		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Tmax of Glyco-OCA at Week 18		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Ctrough of Glyco-OCA at Week 18	Ctrough was considered as the concentration at 24-hours post-dose at Week 18.	24 hours post-dose at Week 18
Primary	AUC0-24h of Glyco-OCA at Week 18	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	MRAUC of Glyco-OCA at Week 18	MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	MRCmax of Glyco-OCA at Week 18	MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Cmax of Glyco-OCA at Week 24		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Tmax of Glyco-OCA at Week 24		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Ctrough of Glyco-OCA at Week 24	Ctrough was considered as the concentration at 24-hours post-dose at Week 24.	24 hours post-dose at Week 24
Primary	AUC0-24h of Glyco-OCA at Week 24	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	MRAUC of Glyco-OCA at Week 24	MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	MRCmax of Glyco-OCA at Week 24	MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Cmax of Glyco-OCA at Week 30		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Tmax of Glyco-OCA at Week 30		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Ctrough of Glyco-OCA at Week 30	Ctrough was considered as the concentration at 24-hours post-dose at Week 30.	24 hours post-dose at Week 30
Primary	AUC0-24h of Glyco-OCA at Week 30	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	MRAUC of Glyco-OCA at Week 30	MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	MRCmax of Glyco-OCA at Week 30	MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Cmax of Glyco-OCA at Week 48		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Tmax of Glyco-OCA at Week 48		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Ctrough of Glyco-OCA at Week 48	Ctrough was considered as the concentration at 24-hours post-dose at Week 48.	24 hours post-dose at Week 48
Primary	AUC0-24h of Glyco-OCA at Week 48	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	MRAUC of Glyco-OCA at Week 48	MRAUC was the ratio of AUC0-24h of Glyco-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	MRCmax of Glyco-OCA at Week 48	MRCmax was the ratio of Cmax of Glyco-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Glyco-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Cmax of Tauro Conjugate of OCA (Tauro-OCA) at Week 12		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Tmax of Tauro-OCA at Week 12		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Ctrough of Tauro-OCA at Week 12	Ctrough was considered as the concentration at 24-hours post-dose at Week 12.	24 hours post-dose at Week 12
Primary	AUC0-24h of Tauro-OCA at Week 12	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	MRAUC of Tauro-OCA at Week 12	MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	MRCmax of Tauro-OCA at Week 12	MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Cmax of Tauro-OCA at Week 18		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Tmax of Tauro-OCA at Week 18		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Ctrough of Tauro-OCA at Week 18	Ctrough was considered as the concentration at 24-hours post-dose at Week 18.	24 hours post-dose at Week 18
Primary	AUC0-24h of Tauro-OCA at Week 18	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	MRAUC of Tauro-OCA at Week 18	MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	MRCmax of Tauro-OCA at Week 18	MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Cmax of Tauro-OCA at Week 24		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Tmax of Tauro-OCA at Week 24		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Ctrough of Tauro-OCA at Week 24	Ctrough was considered as the concentration at 24-hours post-dose at Week 24.	24 hours post-dose at Week 24
Primary	AUC0-24h of Tauro-OCA at Week 24	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	MRAUC of Tauro-OCA at Week 24	MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	MRCmax of Tauro-OCA at Week 24	MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Cmax of Tauro-OCA at Week 30		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Tmax of Tauro-OCA at Week 30		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Ctrough of Tauro-OCA at Week 30	Ctrough was considered as the concentration at 24-hours post-dose at Week 30.	24 hours post-dose at Week 30
Primary	AUC0-24h of Tauro-OCA at Week 30	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	MRAUC of Tauro-OCA at Week 30	MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	MRCmax of Tauro-OCA at Week 30	MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Cmax of Tauro-OCA at Week 48		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Tmax of Tauro-OCA at Week 48		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Ctrough of Tauro-OCA at Week 48	Ctrough was considered as the concentration at 24-hours post-dose at Week 48.	24 hours post-dose at Week 48
Primary	AUC0-24h of Tauro-OCA at Week 48	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	MRAUC of Tauro-OCA at Week 48	MRAUC was the ratio of AUC0-24h of Tauro-OCA (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	MRCmax of Tauro-OCA at Week 48	MRCmax was the ratio of Cmax of Tauro-OCA (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of Tauro-OCA, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Cmax of Glucuronide Metabolite of OCA (OCA-glucuronide) at Week 12		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Tmax of OCA-glucuronide at Week 12		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Ctrough of OCA-glucuronide at Week 12	Ctrough was considered as the concentration at 24-hours post-dose at Week 12.	24 hours post-dose at Week 12
Primary	AUC0-24h of OCA-glucuronide at Week 12	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	MRAUC of OCA-glucuronide at Week 12	MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	MRCmax of OCA-glucuronide at Week 12	MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 12
Primary	Cmax of OCA-glucuronide at Week 18		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Tmax of OCA-glucuronide at Week 18		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Ctrough of OCA-glucuronide at Week 18	Ctrough was considered as the concentration at 24-hours post-dose at Week 18.	24 hours post-dose at Week 18
Primary	AUC0-24h of OCA-glucuronide at Week 18	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	MRAUC of OCA-glucuronide at Week 18	MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	MRCmax of OCA-glucuronide at Week 18	MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 18
Primary	Cmax of OCA-glucuronide at Week 24		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Tmax of OCA-glucuronide at Week 24		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Ctrough of OCA-glucuronide at Week 24	Ctrough was considered as the concentration at 24-hours post-dose at Week 24.	24 hours post-dose at Week 24
Primary	AUC0-24h of OCA-glucuronide at Week 24	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	MRAUC of OCA-glucuronide at Week 24	MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	MRCmax of OCA-glucuronide at Week 24	MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 24
Primary	Cmax of OCA-glucuronide at Week 30		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Tmax of OCA-glucuronide at Week 30		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Ctrough of OCA-glucuronide at Week 30	Ctrough was considered as the concentration at 24-hours post-dose at Week 30.	24 hours post-dose at Week 30
Primary	AUC0-24h of OCA-glucuronide at Week 30	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	MRAUC of OCA-glucuronide at Week 30	MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	MRCmax of OCA-glucuronide at Week 30	MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 30
Primary	Cmax of OCA-glucuronide at Week 48		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Tmax of OCA-glucuronide at Week 48		Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Ctrough of OCA-glucuronide at Week 48	Ctrough was considered as the concentration at 24-hours post-dose at Week 48.	24 hours post-dose at Week 48
Primary	AUC0-24h of OCA-glucuronide at Week 48	AUC0-24h was calculated using the linear/linear trapezoidal rule.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	MRAUC of OCA-glucuronide at Week 48	MRAUC was the ratio of AUC0-24h of OCA-glucuronide (metabolite) to AUC0-24h of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where AUC0-24 is the area under the plasma concentration time profile from time 0 to 24 hours.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	MRCmax of OCA-glucuronide at Week 48	MRCmax was the ratio of Cmax of OCA-glucuronide (metabolite) to Cmax of OCA (parent drug) * ratio of molecular weight of OCA to molecular weight of OCA-glucuronide, where Cmax is the maximum observed concentration.	Pre-dose (30 minutes before administration) and 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, and 24 hours post-dose at Week 48
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.; An SAE was any AE that results in death, was life-threatening, resulted in a persistent or significant disability/incapacity, resulted in in-patient hospitalization or prolonged an existing hospitalization, was a congenital anomaly/birth defect, or was an important medical event that could jeopardize the participant or could have required medical intervention to prevent one of the outcomes listed above.; TEAE was defined as any AE if it met one or more of the following criteria: 1) An AE started on or after the first study drug dose and within 30 days after the last dose of study drug, 2) An AE occurred prior to the first study drug dose that worsens (increase in grade) after the first study drug dose.	Baseline up to approximately 3 years
Secondary	Change From Baseline in the Model of End-stage Liver Disease (MELD) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15	The MELD scoring system is used to assess the severity of chronic liver disease. The MELD score is derived from the participant's serum total bilirubin, serum creatinine, and prothrombin international normalized ratio (INR): 3.78×log normal (ln) [total bilirubin (mg/deciliter [dL])] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.	Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in MELD-Sodium (Na) Score at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15	The MELD-Na scoring system is used to assess the severity of chronic liver disease in the participants with an initial MELD(i) score greater than 11. MELD-Na score is derived from the participant's serum total bilirubin, serum creatinine, INR, and sodium. The MELD-Na score is re-calculated as follows: MELD-Na = MELD(i) + 1.32*(137-Na) - [0.033*MELD(i)*(137-Na)]. MELD score ranges from 6-40 with higher scores indicating more severe liver disease and a worse outcome.; The MELD(i) score is derived from the participant's serum total bilirubin, serum creatinine, and prothrombin international normalized ratio (INR): 3.78×log normal (ln) [total bilirubin (mg/deciliter [dL])] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43. The MELD score ranges from 6 to 40 with higher scores indicating more severe liver disease and a worse outcome.	Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Child-Pugh Score at Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15	The Child-Pugh classification was a scoring system used for the classification of the severity of cirrhosis. It included three continuous variables (bilirubin, albumin, and INR) and two discrete variables (ascites and encephalopathy). Each variable was scored 1-3 with 3 indicating most severe derangement. The determination of Child-Pugh score ranged from 5 to 15. The higher the score, the sicker the participant.	Baseline, Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Number of Participants by Child-Pugh Score Component Category (Ascites Categories)	Number of participants with Child-Pugh component - ascites categories of none, mild, and moderate-severe has been reported. The ascites categories were defined per investigator's discretion.	Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Number of Participants by Child-Pugh Score Component Category (Prothrombin Time Categories)	Number of participants with Child-Pugh component - prothrombin time (measured as INR) in categories of <1.7, 1.7 - 2.3, and >2.3 has been reported.	Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Number of Participants by Child-Pugh Score Component Category (Serum Albumin Categories)	Number of participants with Child-Pugh component - serum albumin levels in categories of >35 gram per liter (g/L), 28-35 g/L, or <28 g/L has been reported.	Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Number of Participants by Child-Pugh Score Component Category (Total Bilirubin Categories)	Number of participants with Child-Pugh component - total bilirubin levels in categories of <34 micromole per liter (µmol/L), 34-50 µmol/L, and >50 µmol/L has been reported.	Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Number of Participants by Child-Pugh Score Component Category (Hepatic Encephalopathy Categories)	Number of participants with Child-Pugh component - Hepatic encephalopathy in categories of Grade 0, Grade 1 or 2, and Grade 3 and 4 has been reported.; Grade 0: normal consciousness, normal personality, normal neurological examination, normal electroencephalogram.; Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cycles, per second (cps) waves.; Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves.; Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves.; Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cps delta activity.	Day 1, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Total Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Direct Bilirubin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Alkaline Phosphatase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Alanine Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Aspartate Aminotransferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Gamma Glutamyl Transferase at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Prothrombin INR at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Creatinine at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Albumin at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Platelets at Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15		Baseline, Weeks 3, 6, 12, 18, 24, 30, 36, 42, and 48; and Extension Months 3, 6, 9, 12, and 15
Secondary	Change From Baseline in Total Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3	Total bile acids (micromole [µM]) = total ursodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in µM + total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in µM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in µM + total cholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in µM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in µM.	Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Secondary	Change From Baseline in Total Endogenous Bile Acids Concentration at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3	Total endogenous bile acids (µM) = total chenodeoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in µM + total deoxycholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in µM + total cholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in µM + total lithocholic acid (unconjugated, glyco-conjugate, tauro-conjugate) in µM.	Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Secondary	Change From Baseline in 7a-hydroxy-4-cholesten-3-one (C4) at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3		Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3
Secondary	Change From Baseline in Fibroblast Growth Factor-19 (FGF-19) Concentrations at Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3		Baseline, Weeks 6, 12, 18, 24, 30, 36, and 48; and Extension Month 3