Obeticholic Acid (OCA) in Primary Sclerosing Cholangitis... | NCT02177136

ID	Type	Description	Link
2014-002205-38	EudraCT Number

Label	Type	Description	Intervention Names
1.5 mg OCA titrating to 3 mg OCA	Experimental	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks during the DB phase. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	Drug: Obeticholic Acid (OCA)
5 mg OCA titrating to 10 mg OCA	Experimental	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks during the DB phase. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	Drug: Obeticholic Acid (OCA)
Placebo	Experimental	Participants randomized to placebo took placebo for 24 weeks during the DB phase.	Drug: Placebo
LTSE OCA Total	Experimental	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.	Drug: Obeticholic Acid (OCA)

Name	Type	Description	Arm Group Labels	Other Names
Obeticholic Acid (OCA)	Drug		1.5 mg OCA titrating to 3 mg OCA 5 mg OCA titrating to 10 mg OCA LTSE OCA Total

Measure	Description	Time Frame
DB Phase: Change From Baseline In Serum Alkaline Phosphatase (ALP)	The primary efficacy analysis compared the Week 24 change from Baseline in ALP between OCA treatment group and placebo using an analysis of covariance (ANCOVA) model with fixed effects for treatment group and randomization strata, and Baseline as a covariate. Results are reported in U/L.	Baseline, Week 24
LTSE Phase: Incidence Of Adverse Events Of Special Interest (AESIs)	The primary safety analysis evaluated the effects of OCA treatment on AESIs of pruritus, hepatic disorders, and dyslipidemia. All adverse event (AE) summaries were restricted to treatment emergent AEs (TEAEs), which were defined as any AEs that newly appeared, increased in frequency, or worsened in severity following initiation of investigational product. Treatment-emergent pruritus was defined as any preferred term (PT) including "Prur-". Hepatic disorder AESIs were defined using specific Hepatic Disorders Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) terms. AE lipid profile changes, defined in the Dyslipidemia SMQ, were reported. Verbatim terms were mapped to PTs and system organ classes (SOCs) using MedDRA version 17.1 for all AE summaries except those for hepatic disorder AESIs, which used MedDRA version 18.1. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.	LTSE Baseline (DB Week 24) to Month 26

Measure	Description	Time Frame
DB Phase: Change From Baseline In Serum Alanine Transaminase (ALT)	As a marker of hepatic biochemistry and liver function, the median change in ALT from Baseline at Week 24 is reported. Results are reported in U/L.	Baseline, Week 24
DB Phase: Change From Baseline In Serum Aspartate Aminotransferase (AST)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Must have had a diagnosis of PSC (based on cholangiography at any point in time).
Alkaline phosphatase at Screening ≥2x ULN.
Total bilirubin at Screening <2.5x ULN.
For participants with concomitant inflammatory bowel disease (IBD):
1. Colonoscopy (if participant has a colon) or other appropriate endoscopic procedure within 12 months of Day 0 confirming no dysplasia or colorectal cancer
2. Participants with Crohn's Disease (CD) must have been in remission as defined by a Crohn's Disease Activity Index (CDAI) <150
3. Participants with ulcerative colitis (UC) must either have been in remission or have had mild disease. Remission was defined as a partial Mayo score of ≤2 with no individual sub-score exceeding 1. Mild disease was defined as a partial Mayo score ≤3 with no individual sub-score exceeding 1 point.
For participants being administered UDCA as part of their standard of care, the dose must have been stable for ≥3 months prior to, and including, Day 0 and must not have exceeded 20 mg/kilograms/day during this time.
Participants being administered biologic treatments (for example, anti-tumor necrosis factor or anti-integrin monoclonal antibodies), immunosuppressants, systemic corticosteroids, or statins, must have been on a stable dose for ≥3 months prior to, and including, Day 0 and should plan to remain on a stable dose throughout the trial.
Contraception: female participants of childbearing potential must have used ≥1 effective method (≤1% failure rate) of contraception during the trial and until 4 weeks following the last dose of IP (including LTSE doses).

Exclusion Criteria:

Evidence of a secondary cause of sclerosing cholangitis at Screening.
Immunoglobulin G4 (IgG4) >4x ULN at Screening or evidence of IgG4 sclerosing cholangitis.
Small duct cholangitis in the absence of large duct disease.
Presence of clinical complications of chronic liver disease or clinically significant hepatic decompensation, including:
- Current Child Pugh classification B or C
- History of, or current diagnosis or suspicion of, cholangiocarcinoma or other hepatobiliary malignancy, or biliary tract dysplasia.
- History of liver transplantation, or current model of end stage liver disease score ≥12
- History of, or current, cirrhosis with complications, including history or presence of spontaneous bacterial peritonitis hepatocellular carcinoma or hepatic encephalopathy (as assessed by the Investigator)
- Current known portal hypertension with complications, including known gastric or large esophageal varices, poorly controlled or diuretic resistant ascites, history of variceal bleeds, or related therapeutic or prophylactic interventions (for example, beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt).
- History of, or current, hepatorenal syndrome (type I or II) or Screening serum creatinine >2 mg/deciliter (178 micromoles/liter [L]).
- Platelet count <50 x 10^9/L.
Current clinical evidence of dominant strictures that were considered clinically relevant in the opinion of the Investigator or current biliary stent at Screening.
Current cholecystitis or evidence of current biliary obstruction due to gallstones. Asymptomatic gallstones that were not considered a safety risk in the opinion of the Investigator might have been acceptable, subject to discussion and agreement with the Medical Monitor.
Colonic dysplasia within ≤5 years prior to Day 0.
History of small bowel resection.
History of other chronic liver diseases, including, but not limited to, primary biliary cholangitis (PBC), alcoholic liver disease, non-alcoholic fatty liver disease, autoimmune hepatitis, hepatitis B virus (unless seroconverted and no positive Hepatitis B Virus deoxyribonucleic acid), hepatitis C virus and overlap syndrome.
Known Gilbert's syndrome or history of elevations in unconjugated (indirect) bilirubin >ULN or unconjugated (indirect) bilirubin >ULN at Screening.
Known history of human immunodeficiency virus infection.
Currently experiencing, or experienced within ≤3 months of Screening, pruritus requiring systemic or enteral treatment.
Known or suspected acute cholangitis in the 3 months prior to, and including, Day 0 including cholangitis treated with antibiotics.
Administration of antibiotics is prohibited ≤1 month of Day 0 (unless participant was on a stable prophylaxis dose for at least 3 months prior to Day 0).
Administration of the following medications was prohibited ≤6 months of Day 0 and throughout the trial: fenofibrate or other fibrates and potentially hepatotoxic medications (including alpha-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin).
IBD flare during Screening (up to and including Day 0), where "flare" was defined as follows:
- UC flare: partial Mayo Score ≥5, and
- CD flare: CDAI ≥250
Evidence of deleterious effects of alcohol abuse (as assessed by the Investigator) or excessive alcohol consumption (>4 units/day for males, >2 units/day for females).
Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated) within 3 months of Day 0.
If female: known pregnancy, or had a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.
Other concomitant disease, malignancy, or condition likely to significantly decrease life expectancy to less than the duration of the trial (for example, moderate to severe congestive heart failure).
Participation in another investigational drug, biologic, or medical device trial within 30 days prior to Screening.
History of noncompliance with medical regimens, or participants who were considered to be potentially unreliable.
Blood or plasma donation within 30 days prior to Day 0.
Mental instability or incompetence such that the validity of informed consent or compliance with the trial was uncertain.

Name	Affiliation	Role
George Harb, MD	Intercept Pharmaceuticals, Inc.	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
St. Joseph's Hospital & Medical Center		Phoenix	Arizona	85013	United States
Mayo Clinic

PubMed Identifier	Type	Citation	Retractions
32165251	Result	Kowdley KV, Vuppalanchi R, Levy C, Floreani A, Andreone P, LaRusso NF, Shrestha R, Trotter J, Goldberg D, Rushbrook S, Hirschfield GM, Schiano T, Jin Y, Pencek R, MacConell L, Shapiro D, Bowlus CL; AESOP Study Investigators. A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis. J Hepatol. 2020 Jul;73(1):94-101. doi: 10.1016/j.jhep.2020.02.033. Epub 2020 Mar 10.

ID	Title	Description
FG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks during the DB phase. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
FG001	5 mg OCA Titrating to 10 mg OCA

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 18, 2016	Feb 23, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

DB Phase: Change From Baseline In Serum Alkaline Phosphatase (ALP)

The primary efficacy analysis compared the Week 24 change from Baseline in ALP between OCA treatment group and placebo using an analysis of covariance (ANCOVA) model with fixed effects for treatment group and randomization strata, and Baseline as a covariate. Results are reported in U/L.

Intent-to-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

Posted

Least Squares Mean

Standard Error

U/L

Baseline, Week 24

ID	Title	Description
OG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
OG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.
OG002	Placebo	Participants randomized to placebo took placebo daily for 24 weeks.

Units	Counts
Participants	OG00025 OG00126 OG00225

Title

Denominators

Categories

Title	Measurements
	OG000-105.05± 38.02 OG001-110.19± 33.77 OG002-26.76± 36.65

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001 OG002		ANCOVA	ANCOVA model with treatment group and randomization stratification factors as fixed effects and baseline as covariate.	0.0434														Superiority
OG000 OG002		ANCOVA

Primary

LTSE Phase: Incidence Of Adverse Events Of Special Interest (AESIs)

The primary safety analysis evaluated the effects of OCA treatment on AESIs of pruritus, hepatic disorders, and dyslipidemia. All adverse event (AE) summaries were restricted to treatment emergent AEs (TEAEs), which were defined as any AEs that newly appeared, increased in frequency, or worsened in severity following initiation of investigational product. Treatment-emergent pruritus was defined as any preferred term (PT) including "Prur-". Hepatic disorder AESIs were defined using specific Hepatic Disorders Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) terms. AE lipid profile changes, defined in the Dyslipidemia SMQ, were reported. Verbatim terms were mapped to PTs and system organ classes (SOCs) using MedDRA version 17.1 for all AE summaries except those for hepatic disorder AESIs, which used MedDRA version 18.1. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase.

Posted

Count of Participants

Participants

LTSE Baseline (DB Week 24) to Month 26

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Secondary

DB Phase: Change From Baseline In Serum Alanine Transaminase (ALT)

As a marker of hepatic biochemistry and liver function, the median change in ALT from Baseline at Week 24 is reported. Results are reported in U/L.

Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

Posted

Median

Inter-Quartile Range

U/L

Baseline, Week 24

ID	Title	Description
OG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
OG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.
OG002	Placebo	Participants randomized to placebo took placebo daily for 24 weeks.

Units	Counts

Secondary

DB Phase: Change From Baseline In Serum Aspartate Aminotransferase (AST)

As a marker of hepatic biochemistry and liver function, the median change in AST from Baseline at Week 24 is reported. Results are reported in U/L.

Intent-to-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

Posted

Median

Inter-Quartile Range

U/L

Baseline, Week 24

ID	Title	Description
OG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
OG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.
OG002	Placebo	Participants randomized to placebo took placebo for 24 weeks.

Units	Counts

Secondary

DB Phase: Change From Baseline In Serum Total Bilirubin

As a marker of hepatic biochemistry and liver function, the median change in serum total bilirubin from Baseline at Week 24 is reported. Results are reported in umol/L.

Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

Posted

Median

Inter-Quartile Range

umol/L

Baseline, Week 24

ID	Title	Description
OG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
OG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.
OG002	Placebo	Participants randomized to placebo took placebo for 24 weeks.

Units	Counts

Secondary

DB Phase: Change From Baseline In Serum Direct Bilirubin

As a marker of hepatic biochemistry and liver function, the median change in serum direct bilirubin from Baseline at Week 24 is reported. Results are reported in umol/L.

Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

Posted

Median

Inter-Quartile Range

umol/L

Baseline, Week 24

ID	Title	Description
OG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
OG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.
OG002	Placebo	Participants randomized to placebo took placebo for 24 weeks.

Units	Counts

Secondary

DB Phase: Change From Baseline In Serum Gamma-glutamyl Transferase (GGT)

As a marker of hepatic biochemistry and liver function, the median change in serum GGT from Baseline at Week 24 is reported. Results are reported in U/L.

Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

Posted

Median

Inter-Quartile Range

U/L

Baseline, Week 24

ID	Title	Description
OG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
OG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.
OG002	Placebo	Participants randomized to placebo took placebo for 24 weeks.

Units	Counts

Secondary

DB Phase: Change From Baseline In Plasma Fibroblast Growth Factor-19 (FGF-19)

To assess farnesoid X receptor (FXR) activity, the change in FGF-19 from Baseline at Week 24 is reported. Results are reported in picograms/milliliter (pg/mL).

Intent-to-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

Posted

Median

Inter-Quartile Range

pg/mL

Baseline, Week 24

ID	Title	Description
OG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
OG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.
OG002	Placebo	Participants randomized to placebo took placebo daily for 24 weeks.

Units

Secondary

DB Phase: Change From Baseline In Plasma 7α-Hydroxy-4-cholesten-3-one (C4)

To assess FXR activity, the change in plasma C4 from Baseline at Week 24 is reported. Results are reported in nanograms (ng)/mL.

Intent-To-Treat Population: All randomized participants who received any amount of investigational product within the DB phase.

Posted

Median

Inter-Quartile Range

ng/mL

Baseline, Week 24

ID	Title	Description
OG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
OG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.
OG002	Placebo	Participants randomized to placebo took placebo for 24 weeks.

Units	Counts

Secondary

LTSE Phase: Change From Baseline In Serum ALP At Month 12

The median change in serum ALP from Baseline to the last available visit is reported. The DB value at Week 24 was used as the Baseline. Results are reported in U/L.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

U/L

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Serum ALT At Month 12

As a marker of hepatic biochemistry and liver function, the median change in ALT from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in U/L.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

U/L

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Serum AST At Month 12

As a marker of hepatic biochemistry and liver function, the median change in AST from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in U/L.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

U/L

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Serum Total Bilirubin At Month 12

As a marker of hepatic biochemistry and liver function, the median change in serum total bilirubin from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in umol/L.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

umol/L

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Serum Direct Bilirubin At Month 12

As a marker of hepatic biochemistry and liver function, the median change in serum direct bilirubin from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in umol/L.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

umol/L

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Serum GGT At Month 12

As a marker of hepatic biochemistry and liver function, the median change in serum GGT from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in U/L.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

U/L

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Albumin At Month 12

As a marker of hepatic biochemistry and liver function, the median change in albumin from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in grams (g)/L.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

g/L

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In INR At Month 12

As a marker of hepatic biochemistry and liver function, the median change in INR from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

Ratio

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Transient Elastography (TE) At Month 12

As a marker of hepatic inflammation and fibrosis, the median change in TE, as a measure of hepatic stiffness, from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in kilopascal (kPa).

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

kPa

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Enhanced Liver Fibrosis (ELF) At Month 12

As a marker of hepatic inflammation and fibrosis, the change in ELF score from Baseline at Month 12 is reported. The ELF score and its components (hyaluronic acid [HA]; procollagen-3 N-terminal peptide [P3NP]; tissue inhibitor of metalloproteinase 1 [TIMP-1]) was calculated as follows: 2.278 + 0.851 x ln(HA (ng/mL)) + 0.751 x ln(P3NP (ng/mL)) + 0.394 x ln(TIMP-1 (ng/mL). The DB value at Week 24 was used as the Baseline. An increase in score indicates an improvement/worsening of symptoms.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

Units on a scale

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants

Secondary

LTSE Phase: Change From Baseline In Plasma FGF-19 At Month 12

To assess FXR activity, the change in FGF-19 from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in pg/mL.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

pg/mL

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Plasma C4 At Month 12

To assess FXR activity, the change in plasma C4 from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in ng/mL.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

ng/mL

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Participants Experiencing Ulcerative Colitis Remission At Month 12

To assess inflammatory bowel disease (IBD) activity, the number of participants experiencing ulcerative colitis remission at Month 12 is reported. Remission was defined as a partial Mayo score of ≤2 with no individual sub-score exceeding 1 point.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase.

Posted

Number

participants

Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Participants Experiencing Crohn's Disease Remission At Month 12

To assess IBD activity, the number of participants experiencing Crohn's Disease remission at Month 12 is reported. Remission was defined as a Crohn's Disease Activity Index score of <150.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase.

Posted

Number

participants

Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Total Bile Acids At Month 12

To assess the effects on bile acids, the median change in total bile acids from Baseline at Month 12 is reported. The DB value at Week 24 was used as the Baseline. Results are reported in umol/L.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

umol/L

Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants	OG000

Secondary

LTSE Phase: Change From Baseline In Pruritus Visual Analogue Scale (VAS) At Month 12

To assess the effects on disease-specific symptoms, the median change in the pruritus VAS score from Baseline at Month 12 is reported. The score is derived from the VAS participant questionnaire, which has the participant draw a line anywhere on a scale that best represents the severity of the itch; the scale ranges from 0 (no itching) to 10 (worst possible itching), in increments of 2. An increase in score represents an increase in severity of symptoms. The DB value at Week 24 was used as the Baseline.

LTSE Population: All participants who received any amount of investigational product during the LTSE phase and had an efficacy assessment at the specified time points.

Posted

Median

Inter-Quartile Range

units on a scale

LTSE Baseline (DB Week 24), Month 12

ID	Title	Description
OG000	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bile duct stenosis	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG0030 events0 affected59 at risk
Cholangitis	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected27 at risk EG0020 events0 affected24 at risk EG003
Cholangitis acute	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected27 at risk EG0020 events0 affected24 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0021 events1 affected24 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected27 at risk EG0021 events1 affected24 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Oesophageal varices haemorrhage	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0021 events1 affected24 at risk EG003
Cholangitis infective	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Pharyngitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected27 at risk EG0020 events0 affected24 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0011 events1 affected27 at risk EG0020 events0 affected24 at risk EG003
Pseudomonal sepsis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Oedema peripheral	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Peripheral swelling	General disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Colon dysplasia	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Crohn's disease	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Pouchitis	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Bile duct obstruction	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Peritonitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Abdominal abscess	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Enteritis infectious	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Pelvic abscess	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Perirectal abscess	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Pneumonia pneumococcal	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Anastomotic leak	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Delayed recovery from anaesthesia	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Forearm fracture	Injury, poisoning and procedural complications	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG00031 events15 affected25 at risk EG00138 events18 affected27 at risk EG00217 events11 affected24 at risk EG00362 events33 affected59 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected25 at risk EG0017 events6 affected27 at risk EG0023 events3 affected24 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected25 at risk EG0013 events2 affected27 at risk EG0025 events4 affected24 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0013 events3 affected27 at risk EG0023 events2 affected24 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events1 affected25 at risk EG0012 events2 affected27 at risk EG0024 events4 affected24 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0012 events1 affected27 at risk EG0022 events1 affected24 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected27 at risk EG0020 events0 affected24 at risk EG003
Crohn's disease	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected27 at risk EG0021 events1 affected24 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0011 events1 affected27 at risk EG0024 events4 affected24 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events1 affected25 at risk EG0010 events0 affected27 at risk EG0022 events2 affected24 at risk EG003
Frequent bowel movements	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0023 events2 affected24 at risk EG003
Sinusitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0013 events3 affected27 at risk EG0020 events0 affected24 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected25 at risk EG0011 events1 affected27 at risk EG0022 events2 affected24 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0023 events3 affected24 at risk EG003
Pyrexia	General disorders	MedDRA (17.1)	Systematic Assessment	EG0005 events3 affected25 at risk EG0014 events4 affected27 at risk EG0021 events1 affected24 at risk EG003
Fatigue	General disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events1 affected25 at risk EG0013 events3 affected27 at risk EG0022 events2 affected24 at risk EG003
Oedema peripheral	General disorders	MedDRA (17.1)	Systematic Assessment	EG0003 events1 affected25 at risk EG0012 events2 affected27 at risk EG0020 events0 affected24 at risk EG003
Headache	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0003 events2 affected25 at risk EG0012 events2 affected27 at risk EG0020 events0 affected24 at risk EG003
Dizziness	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0013 events2 affected27 at risk EG0020 events0 affected24 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected27 at risk EG0020 events0 affected24 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0013 events3 affected27 at risk EG0023 events3 affected24 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (17.1)	Systematic Assessment	EG0003 events2 affected25 at risk EG0010 events0 affected27 at risk EG0022 events2 affected24 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0005 events2 affected25 at risk EG0011 events1 affected27 at risk EG0021 events1 affected24 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0022 events2 affected24 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected27 at risk EG0020 events0 affected24 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected25 at risk EG0011 events1 affected27 at risk EG0021 events1 affected24 at risk EG003
Bile duct stenosis	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events2 affected25 at risk EG0013 events3 affected27 at risk EG0021 events1 affected24 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0011 events1 affected27 at risk EG0023 events3 affected24 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0022 events2 affected24 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0023 events3 affected24 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0013 events3 affected27 at risk EG0021 events1 affected24 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected27 at risk EG0020 events0 affected24 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0012 events2 affected27 at risk EG0020 events0 affected24 at risk EG003
Colitis ulcerative	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0021 events1 affected24 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Varices oesophageal	Gastrointestinal disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0023 events1 affected24 at risk EG003
Portal hypertension	Hepatobiliary disorders	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Bronchitis	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Influenza	Infections and infestations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0010 events0 affected27 at risk EG0021 events1 affected24 at risk EG003
Liver function test abnormal	Investigations	MedDRA (17.1)	Systematic Assessment	EG0000 events0 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (17.1)	Systematic Assessment	EG0002 events1 affected25 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (17.1)	Systematic Assessment	EG0001 events1 affected25 at risk EG0011 events1 affected27 at risk EG0023 events1 affected24 at risk EG003

ID	Term
D002761	Cholangitis
D001649	Bile Duct Diseases
D001660	Biliary Tract Diseases
D004066	Digestive System Diseases

ID	Title	Description
BG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.
BG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.
BG002	Placebo	Participants randomized to placebo took placebo for 24 weeks.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	1.5 mg OCA Titrating to 3 mg OCA	Participants randomized to 1.5 mg OCA took 1.5 mg OCA daily for 12 weeks during the DB phase. If tolerated, the dose was increased to 3 mg OCA daily for an additional 12 weeks.	25	4	25	20	25
EG001	5 mg OCA Titrating to 10 mg OCA	Participants randomized to 5 mg OCA took 5 mg OCA daily for 12 weeks during the DB phase. If tolerated, the dose was increased to 10 mg OCA daily for an additional 12 weeks.	27	4	27	24	27
EG002	Placebo	Participants randomized to placebo took placebo daily for 24 weeks during the DB phase.	24	2	24	21	24
EG003	LTSE OCA Total	Following completion of the DB phase, participants were asked to reconfirm their consent for participation in the LTSE phase (planned as a further 24 months) beginning at 5 or 10 mg OCA, based on the last treatment received during the DB phase. Doses up to 10 mg daily were evaluated. All participants received open-label OCA during the LTSE phase of the study.	59	19	59	53	59