Trial Outcomes & Findings for Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NCT NCT03439254)

NCT ID: NCT03439254

Last Updated: 2023-10-23

Results Overview

Fibrosis stage was evaluated by NASH Clinical Research Network(CRN)Fibrosis Staging System with stages:0=no fibrosis;1=perisinusoidal/periportal;1A=mild,zone 3,perisinusoidal;1B=moderate,zone 3,perisinusoidal;1C=portal/periportal;2=perisinusoidal and portal/periportal;3=bridging fibrosis;4=cirrhosis.No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant nonalcoholic fatty liver disease activity score (NAS) categories.NAS is semiquantitative scoring system based on unweighted sum of:steatosis (0=\<5% to 3=\>66%),lobular inflammation(0=no foci to 3=\>4 foci/200x),hepatocellular ballooning(0=none to 2=many cells/prominent ballooning)scores.Total scale range:0-12;0:no features of fatty liver disease and 12:highest degree of fatty liver disease.Higher scores:worse symptoms.Responders:did not discontinue treatment due to Adverse event(AE) or did not die and had evaluable post-Baseline biopsy assessment

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 919 participants
• Primary outcome timeframe: Up to 18 months
• Results posted on: 2023-10-23

Participant Flow

The study was conducted at a total of around 286 centers.

This was a Phase 3, double-Blind, randomized, placebo-controlled, multicenter study to evaluate the efficacy and safety of Obeticholic Acid (OCA) in participants with compensated cirrhosis due to Nonalcoholic Steatohepatitis (NASH). The study comprised of a double-blind (DB) phase (18 months) followed by Open-label extension (OLE) phase (12 months).

Participant milestones

Measure	DB: Placebo Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.	OLE: OCA 10 mg (DB Placebo) Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to placebo in the DB phase were re-randomized to either receive OCA 10 mg or titrated dose of OCA 25 mg. Uptitration was determined based on the same criteria and assessments as employed in the DB phase.	OLE: OCA 10 mg (DB OCA 10 mg) Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to OCA 10 mg during the DB phase continued the same dosing regimen they received at the end of the DB Phase; however, they underwent dummy titration to maintain study blind until all participants completed the DB phase.	OLE: Titrated to OCA 25 mg (DB OCA 10 mg Titrated to OCA 25 mg) Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to OCA 10 mg to 25 mg titration during the DB phase continued the same dosing regimen they received at the end of the DB Phase; however, they underwent dummy titration to maintain study blind until all participants completed the DB phase.
Double-blind Phase (18 Months) STARTED	313	296	310	0	0	0
Double-blind Phase (18 Months) COMPLETED	284	274	275	0	0	0
Double-blind Phase (18 Months) NOT COMPLETED	29	22	35	0	0	0
Open Label Extension Phase (12 Months) STARTED	0	0	0	231	221	207
Open Label Extension Phase (12 Months) COMPLETED	0	0	0	215	208	192
Open Label Extension Phase (12 Months) NOT COMPLETED	0	0	0	16	13	15

Reasons for withdrawal

Measure	DB: Placebo Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.	OLE: OCA 10 mg (DB Placebo) Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to placebo in the DB phase were re-randomized to either receive OCA 10 mg or titrated dose of OCA 25 mg. Uptitration was determined based on the same criteria and assessments as employed in the DB phase.	OLE: OCA 10 mg (DB OCA 10 mg) Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to OCA 10 mg during the DB phase continued the same dosing regimen they received at the end of the DB Phase; however, they underwent dummy titration to maintain study blind until all participants completed the DB phase.	OLE: Titrated to OCA 25 mg (DB OCA 10 mg Titrated to OCA 25 mg) Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to OCA 10 mg to 25 mg titration during the DB phase continued the same dosing regimen they received at the end of the DB Phase; however, they underwent dummy titration to maintain study blind until all participants completed the DB phase.
Double-blind Phase (18 Months) Adverse Event	11	12	15	0	0	0
Double-blind Phase (18 Months) Covid-19 Non Adverse Event (AE) Related Issues	1	0	0	0	0	0
Double-blind Phase (18 Months) Death	1	2	2	0	0	0
Double-blind Phase (18 Months) Lost to Follow-up	0	1	5	0	0	0
Double-blind Phase (18 Months) Non-Compliance With Study Drug	1	0	0	0	0	0
Double-blind Phase (18 Months) Participant moved to Kansas	1	0	0	0	0	0
Double-blind Phase (18 Months) Site cover and participant was not willing to be transferred	1	0	0	0	0	0
Double-blind Phase (18 Months) Stopped Investigational product (IP) due to an AE in Australia	0	1	0	0	0	0
Double-blind Phase (18 Months) Drug Holiday	0	0	1	0	0	0
Double-blind Phase (18 Months) Spouse underwent surgery and participant was unable to take IP regularly	0	0	1	0	0	0
Double-blind Phase (18 Months) Site closure	0	0	1	0	0	0
Double-blind Phase (18 Months) Physician Decision	0	0	1	0	0	0
Double-blind Phase (18 Months) Progressive Disease	1	0	0	0	0	0
Double-blind Phase (18 Months) Withdrawal by Subject	12	6	9	0	0	0
Open Label Extension Phase (12 Months) Adverse Event	0	0	0	8	5	7
Open Label Extension Phase (12 Months) Bariatric Surgery	0	0	0	1	0	1
Open Label Extension Phase (12 Months) Covid-19 Non-AE Related Issues	0	0	0	0	0	1
Open Label Extension Phase (12 Months) Lost to Follow-up	0	0	0	0	2	0
Open Label Extension Phase (12 Months) Increase CR from Baseline	0	0	0	0	1	0
Open Label Extension Phase (12 Months) Medical reasons by Sponsor	0	0	0	0	0	1
Open Label Extension Phase (12 Months) Physician Decision	0	0	0	1	0	0
Open Label Extension Phase (12 Months) Progressive Disease	0	0	0	1	2	0
Open Label Extension Phase (12 Months) Withdrawal by Subject	0	0	0	5	3	5

Baseline Characteristics

Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis

Baseline characteristics by cohort

Measure	DB: Placebo n=313 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=296 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=310 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.	Total n=919 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Hispanic or Latino	44 Participants n=5 Participants	52 Participants n=7 Participants	55 Participants n=5 Participants	151 Participants n=4 Participants
Age, Continuous	59.5 Years STANDARD_DEVIATION 8.99 • n=5 Participants	60.1 Years STANDARD_DEVIATION 8.70 • n=7 Participants	60.1 Years STANDARD_DEVIATION 8.67 • n=5 Participants	59.9 Years STANDARD_DEVIATION 8.78 • n=4 Participants
Sex: Female, Male Female	212 Participants n=5 Participants	184 Participants n=7 Participants	209 Participants n=5 Participants	605 Participants n=4 Participants
Sex: Female, Male Male	101 Participants n=5 Participants	112 Participants n=7 Participants	101 Participants n=5 Participants	314 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	246 Participants n=5 Participants	217 Participants n=7 Participants	233 Participants n=5 Participants	696 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	23 Participants n=5 Participants	27 Participants n=7 Participants	22 Participants n=5 Participants	72 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) White	272 Participants n=5 Participants	254 Participants n=7 Participants	272 Participants n=5 Participants	798 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	25 Participants n=5 Participants	25 Participants n=7 Participants	21 Participants n=5 Participants	71 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 18 months

Population: ITT Population.

Fibrosis stage was evaluated by NASH Clinical Research Network(CRN)Fibrosis Staging System with stages:0=no fibrosis;1=perisinusoidal/periportal;1A=mild,zone 3,perisinusoidal;1B=moderate,zone 3,perisinusoidal;1C=portal/periportal;2=perisinusoidal and portal/periportal;3=bridging fibrosis;4=cirrhosis.No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant nonalcoholic fatty liver disease activity score (NAS) categories.NAS is semiquantitative scoring system based on unweighted sum of:steatosis (0=<5% to 3=>66%),lobular inflammation(0=no foci to 3=>4 foci/200x),hepatocellular ballooning(0=none to 2=many cells/prominent ballooning)scores.Total scale range:0-12;0:no features of fatty liver disease and 12:highest degree of fatty liver disease.Higher scores:worse symptoms.Responders:did not discontinue treatment due to Adverse event(AE) or did not die and had evaluable post-Baseline biopsy assessment

Outcome measures

Measure	DB: Placebo n=313 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=296 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=310 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
DB Phase: Number of Participants Who Were Responders and Showed Improvement in Fibrosis by at Least 1 Stage Without Worsening of Nonalcoholic Steatohepatitis (NASH)	31 Participants	33 Participants	37 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo).

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.

Outcome measures

Measure	DB: Placebo n=231 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=221 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=207 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
OLE Phase: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	199 Participants	213 Participants	197 Participants
OLE Phase: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	26 Participants	50 Participants	48 Participants

PRIMARY outcome

Timeframe: Baseline and up to Month 12

Population: ITT Population. Only those participants with data available at the specified data points were analyzed.

Non-invasive radiological methods to assess liver stiffness were conducted at selected study sites where the respective devices were available. These assessments were taken by vibration controlled transient elastography (TE) method using FibroScan®. Participant was included as a random effect and an unstructured covariance matrix was used assuming convergence could be attained. Baseline was defined as the last value collected prior to the first administration of the investigational product (IP). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Outcome measures

Measure	DB: Placebo n=177 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=172 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=160 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
OLE Phase: Change From Baseline to Month 12 in Liver Stiffness Measurement (LSM)	-2.10 Kilopascal (kPa) Interval -7.4 to 3.4	-2.90 Kilopascal (kPa) Interval -7.75 to 1.35	-3.45 Kilopascal (kPa) Interval -7.85 to 0.75

PRIMARY outcome

Timeframe: Baseline (Day 1)

Population: ITT Population. Only those participants with data available at the specified data points were analyzed.

FIB-4 was a noninvasive assessment of liver disease assessed by a combination of age, alanine aminotransferase (ALT) and platelet results. FIB-4 was the ratio of age in years and aminotransferase to platelet count. It was a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, ALT, Aspartate aminotransferase (AST) and age that was calculated using formula: FIB-4 = (Age [years] x AST [Units per Liter {U/L}]) / (platelets [10^9/L] x (square root of ALT [U/L])). A FIB-4 index of <1.45 indicated no or moderate fibrosis and an index of > 3.25 indicated extensive fibrosis/cirrhosis. Higher ratio indicated worse condition. Baseline was defined as the last value collected prior to the first administration of the IP.

Outcome measures

Measure	DB: Placebo n=230 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=221 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=207 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
OLE Phase: Fibrosis-4 (FIB-4) at Baseline	2.179 Ratio Standard Deviation 1.0342	2.267 Ratio Standard Deviation 0.9567	2.266 Ratio Standard Deviation 1.0867

PRIMARY outcome

Timeframe: Baseline (Day 1)

Population: ITT Population. Only those participants with data available at the specified data points were analyzed.

ELF was non-invasive panel of circulating fibrosis markers calculated from serum biomarkers. The markers of fibrosis comprised hyaluronic acid (HA), tissue inhibitor of metalloproteinase (TIMP1) and procollagen III N-terminal peptide (PIIINP). Each of these markers was measured by an immunoassay and an ELF score was generated, from which a level of fibrosis severity could be determined. The ELF test was a composite score: < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis.; higher ELF scores were associated with worsening liver fibrosis. Baseline was defined as the last value collected prior to the first administration of the IP.

Outcome measures

Measure	DB: Placebo n=227 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=220 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=206 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
OLE Phase: Enhanced Liver Fibrosis (ELF) at Baseline	10.46 Scores on a scale Standard Deviation 0.933	10.50 Scores on a scale Standard Deviation 0.940	10.48 Scores on a scale Standard Deviation 0.821

PRIMARY outcome

Timeframe: Up to Month 12

Population: Safety Population

All-cause mortality is defined as death due to any cause. Number of participants reporting all-cause mortality is presented

Outcome measures

Measure	DB: Placebo n=231 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=221 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=207 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
OLE Phase: Number of Participants Reporting All-cause Mortality	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: Safety Population

Adjudication was performed under the review of Hepatic Safety Adjudication Committee (HSAC) of all available data for each identified participant to determine liver injury status. Number of participants with adjudicated liver related clinical outcomes for the following is presented: Ascites (secondary to cirrhosis and requiring medical intervention), Hepatocellular carcinoma (HCC) and non-liver related death.

Outcome measures

Measure	DB: Placebo n=231 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=221 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=207 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Ascites, Hepatocellular Carcinoma (HCC) and Non-liver Related Death Ascites (secondary to cirrhosis and requiring medical intervention)	1 Participants	0 Participants	2 Participants
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Ascites, Hepatocellular Carcinoma (HCC) and Non-liver Related Death HCC	3 Participants	1 Participants	1 Participants
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Ascites, Hepatocellular Carcinoma (HCC) and Non-liver Related Death Non-liver related death	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: Safety Population

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 international normalized ratio) 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. Adjudication was performed under the review of HSAC of all available data for each identified participant to determine liver injury status. Number of participants with adjudicated liver related clinical outcomes for worsening of Child-Pugh score is presented.

Outcome measures

Measure	DB: Placebo n=231 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=221 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=207 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Worsening of Child-Pugh Score	0 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: Safety Population

MELD was a scoring system for assessing the severity of chronic liver disease and to assess prognosis and suitability for liver transplantation. It uses the participant's values for total bilirubin, serum creatinine, and the international normalized ratio for prothrombin time to predict survival. MELD score ranges from 6 (less ill) to 40 (gravely ill) with scores and mortality probability being: Score 40=71.3% mortality; Scores 30-39=52.6% mortality; Scores 20-29=19.6% mortality; Scores10-19=6.0% mortality; Score 9 or less=1.9% mortality. Higher scores indicated greater disease severity. Adjudication was performed under the review of HSAC of all available data for each identified participant to determine liver injury status. Number of participants with adjudicated liver related clinical outcomes for MELD score ≥15 is presented.

Outcome measures

Measure	DB: Placebo n=231 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=221 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=207 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Model for End-Stage Liver Disease (MELD) Score ≥15	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and up to Month 18

Population: ITT Population. Only those participants with data available at the specified data points were analyzed.

Non-invasive radiological methods to assess liver stiffness were conducted at selected study sites where the respective devices were available. These assessments were taken by vibration controlled TE method using FibroScan®. Participant was included as a random effect and an unstructured covariance matrix was used assuming convergence could be attained. The principal comparison was at Month 18. Baseline was defined as the last value collected prior to the first administration of the IP. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Outcome measures

Measure	DB: Placebo n=189 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=174 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=173 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
DB Phase: Change From Baseline to Month 18 in LSM	-0.50 Kilopascal (kPa) Interval -5.2 to 5.6	-3.10 Kilopascal (kPa) Interval -7.3 to 3.2	-2.90 Kilopascal (kPa) Interval -8.1 to 2.5

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: ITT Population. Only those participants with data available at the specified data points were analyzed.

FIB-4 was a noninvasive assessment of liver disease assessed by a combination of age, ALT and platelet results. FIB-4 was the ratio of age in years and aminotransferase to platelet count. It was a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, ALT, AST and age that was calculated using formula: FIB-4 = (Age [years] x AST [U/L]) / (platelets [10^9/L] x (square root of ALT [U/L])). A FIB-4 index of <1.45 indicated no or moderate fibrosis and an index of > 3.25 indicated extensive fibrosis/cirrhosis. Higher ratio indicated worse condition. Baseline was defined as the last value collected prior to the first administration of the IP.

Outcome measures

Measure	DB: Placebo n=311 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=295 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=308 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
DB Phase: FIB-4 at Baseline	2.279 Ratio Standard Deviation 1.1091	2.475 Ratio Standard Deviation 1.9307	2.405 Ratio Standard Deviation 1.1630

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: ITT Population. Only those participants with data available at the specified data points were analyzed.

ELF was non-invasive panel of circulating fibrosis markers calculated from serum biomarkers. The markers of fibrosis comprised HA, TIMP1 and PIIINP. Each of these markers was measured by an immunoassay and an ELF score was generated, from which a level of fibrosis severity could be determined. The ELF test was a composite score: < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis.; higher ELF scores were associated with worsening liver fibrosis. Baseline was defined as the last value collected prior to the first administration of the IP.

Outcome measures

Measure	DB: Placebo n=307 Participants Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=294 Participants Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=307 Participants Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.
DB Phase: ELF at Baseline	10.50 Scores on a scale Standard Deviation 0.921	10.60 Scores on a scale Standard Deviation 0.920	10.61 Scores on a scale Standard Deviation 0.867

Adverse Events

DB: Placebo

Serious events: 43 serious events

Other events: 290 other events

Deaths: 4 deaths

DB: OCA 10 Milligrams (mg)

Serious events: 49 serious events

Other events: 276 other events

Deaths: 3 deaths

DB: OCA 10 mg Titrated to OCA 25 mg

Serious events: 46 serious events

Other events: 291 other events

Deaths: 3 deaths

OLE: OCA 10 mg (DB Placebo)

Serious events: 26 serious events

Other events: 199 other events

Deaths: 1 deaths

OLE: OCA 10 mg (DB OCA 10 mg)

Serious events: 50 serious events

Other events: 213 other events

Deaths: 0 deaths

OLE: Titrated to OCA 25 mg (DB OCA 10 mg Titrated to OCA 25 mg)

Serious events: 48 serious events

Other events: 197 other events

Deaths: 1 deaths

Serious adverse events

Measure	DB: Placebo n=312 participants at risk Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=295 participants at risk Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=309 participants at risk Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.	OLE: OCA 10 mg (DB Placebo) n=231 participants at risk Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to placebo in the DB phase were re-randomized to either receive OCA 10 mg or titrated dose of OCA 25 mg. Uptitration was determined based on the same criteria and assessments as employed in the DB phase.	OLE: OCA 10 mg (DB OCA 10 mg) n=221 participants at risk Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to OCA 10 mg during the DB phase continued the same dosing regimen they received at the end of the DB Phase; however, they underwent dummy titration to maintain study blind until all participants completed the DB phase.	OLE: Titrated to OCA 25 mg (DB OCA 10 mg Titrated to OCA 25 mg) n=207 participants at risk Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to OCA 10 mg to 25 mg titration during the DB phase continued the same dosing regimen they received at the end of the DB Phase; however, they underwent dummy titration to maintain study blind until all participants completed the DB phase.
Hepatobiliary disorders Cholecystitis acute	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Blood and lymphatic system disorders Anaemia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Blood and lymphatic system disorders Bicytopenia	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Blood and lymphatic system disorders Blood loss anaemia	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Acute left ventricular failure	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Acute myocardial infarction	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Angina pectoris	0.64% 2/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Angina unstable	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Cardiac failure acute	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Coronary artery disease	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Left ventricular failure	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Myocardial infarction	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Palpitations	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Pericardial effusion	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Sinus bradycardia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Sinus tachycardia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Ventricular extrasystoles	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Atrial fibrillation	0.96% 3/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.87% 2/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Cardiac arrest	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Cardiogenic shock	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Coronary artery occlusion	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Bradycardia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.87% 2/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.7% 6/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.9% 8/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Acute coronary syndrome	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Cardiac disorders Aortic valve incompetence	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Ear and labyrinth disorders Vertigo	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Ear and labyrinth disorders Vertigo positional	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Eye disorders Blindness unilateral	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Abdominal pain upper	0.64% 2/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 2/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Ascites	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Faecaloma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Pancreatitis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Umbilical hernia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Abdominal pain lower	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Colitis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Cryptitis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Gastrointestinal polyp haemorrhage	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Intra-abdominal haematoma	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Vomiting	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Abdominal hernia obstructive	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Gastritis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Haematochezia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Ileus	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Enteritis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Large intestine polyp	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.90% 2/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Non-cardiac chest pain	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.87% 2/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Adverse drug reaction	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Asthenia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Event leading to Death	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Impaired healing	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Hepatobiliary disorders Hepatic failure	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Oedema peripheral	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Granuloma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Systemic inflammatory response syndrome	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Pyrexia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Hepatobiliary disorders Bile duct stone	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Hepatobiliary disorders Cholelithiasis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.68% 2/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Hepatobiliary disorders Cholecystitis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Hepatobiliary disorders Hepatorenal syndrome	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Hepatobiliary disorders Hydrocholecystis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Hepatobiliary disorders Hepatic lesion	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Hepatobiliary disorders Haemobilia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Immune system disorders Drug hypersensitivity	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Immune system disorders Anaphylactic reaction	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations COVID-19 pneumonia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.68% 2/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 3/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.3% 3/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.90% 2/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.4% 7/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Urinary tract infection	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.65% 2/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 2/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations COVID-19	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.4% 3/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 3/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 2/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Campylobacter infection	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Cellulitis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.90% 2/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Cellulitis staphylococcal	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Diverticulitis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Epididymitis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Escherichia bacteraemia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Escherichia urinary tract infection	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Localised infection	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Pyelonephritis acute	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Suspected COVID-19	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Abscess limb	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Escherichia sepsis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Gastroenteritis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Peritonitis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Sepsis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Septic shock	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Cryptococcal fungaemia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Endocarditis enterococcal	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Influenza	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Urosepsis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Bursitis infective	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Orchitis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Procedural pain	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 3/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.9% 4/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.68% 2/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Accident	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Ligament rupture	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Limb crushing injury	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Post procedural fever	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Joint injury	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Sternal fracture	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Fall	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Metabolism and nutrition disorders Dehydration	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Metabolism and nutrition disorders Gout	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Posterior tibial tendon dysfunction	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Lupus-like syndrome	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Spinal stenosis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.0% 3/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.87% 2/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.90% 2/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.90% 2/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 2/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign salivary gland neoplasm	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Extramammary Paget's disease	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal squamous cell carcinoma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B precursor type acute leukaemia	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour of the small bowel	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal tract adenoma	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma recurrent	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Cerebrovascular accident	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 3/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 2/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Hepatic encephalopathy	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Syncope	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.68% 2/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Brain stem infarction	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Hypoaesthesia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Ischaemic stroke	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Migraine	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Paraesthesia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Meningoradiculitis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Transient ischaemic attack	0.64% 2/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Encephalopathy	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Presyncope	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Depressed level of consciousness	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Facial paralysis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Myelopathy	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Psychiatric disorders Mental status changes	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.68% 2/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Psychiatric disorders Adjustment disorder	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Psychiatric disorders Anxiety	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Psychiatric disorders Panic attack	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Renal and urinary disorders Acute kidney injury	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.48% 1/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Renal and urinary disorders Nephrolithiasis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Renal and urinary disorders Renal colic	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.97% 3/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.4% 3/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary dissease	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Skin and subcutaneous tissue disorders Rash vesicular	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Skin and subcutaneous tissue disorders Panniculitis	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Skin and subcutaneous tissue disorders Rash	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Skin and subcutaneous tissue disorders Blister	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Vascular disorders Aortic stenosis	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Vascular disorders Hypertensive emergency	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.34% 1/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Vascular disorders Hypertensive urgency	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.32% 1/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Vascular disorders Hypertension	0.32% 1/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Endocrine disorders Cushing's syndrome	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Endocrine disorders Hyperthyroidism	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.45% 1/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.

Other adverse events

Measure	DB: Placebo n=312 participants at risk Participants were randomized to receive placebo once daily orally with water, in conjunction with local standard of care.	DB: OCA 10 Milligrams (mg) n=295 participants at risk Participants were randomized to receive OCA 10 mg once daily dosing orally with water, in conjunction with local standard of care.	DB: OCA 10 mg Titrated to OCA 25 mg n=309 participants at risk Participants were randomized to receive OCA 10 mg for the first 3 months prior to uptitrating to OCA 25 mg at Month 3, once daily dosing orally with water, in conjunction with local standard of care. Uptitration was determined based on the laboratory criteria and safety and tolerability assessments completed prior to Month 3. If uptitration at Month 3 was not feasible, the window for uptitration was extended by up to one calendar month, after consultation and agreement with the Medical Monitor.	OLE: OCA 10 mg (DB Placebo) n=231 participants at risk Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to placebo in the DB phase were re-randomized to either receive OCA 10 mg or titrated dose of OCA 25 mg. Uptitration was determined based on the same criteria and assessments as employed in the DB phase.	OLE: OCA 10 mg (DB OCA 10 mg) n=221 participants at risk Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to OCA 10 mg during the DB phase continued the same dosing regimen they received at the end of the DB Phase; however, they underwent dummy titration to maintain study blind until all participants completed the DB phase.	OLE: Titrated to OCA 25 mg (DB OCA 10 mg Titrated to OCA 25 mg) n=207 participants at risk Participants who completed the DB phase (and continued to receive investigational product) were eligible to enroll into the OLE phase. All participants received OCA upon entry into the OLE phase. Participants randomized to OCA 10 mg to 25 mg titration during the DB phase continued the same dosing regimen they received at the end of the DB Phase; however, they underwent dummy titration to maintain study blind until all participants completed the DB phase.
Gastrointestinal disorders Nausea	13.8% 43/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.8% 32/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	15.5% 48/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.2% 19/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	12.7% 28/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	18.8% 39/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Constipation	6.4% 20/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.5% 28/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.7% 33/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.2% 12/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	11.8% 26/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	13.5% 28/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Abdominal pain	6.4% 20/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.5% 31/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.8% 24/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.3% 10/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	11.3% 25/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.6% 22/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Abdominal pain upper	9.3% 29/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.2% 30/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.4% 23/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.2% 12/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	14.0% 31/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.7% 18/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Diarrhoea	12.2% 38/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.5% 28/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.1% 22/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.2% 12/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.9% 24/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.7% 20/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Abdominal distension	6.7% 21/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.1% 24/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.4% 23/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.7% 4/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.0% 22/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.1% 21/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Vomiting	5.8% 18/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.8% 20/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.1% 25/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.8% 11/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.3% 14/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.1% 21/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Varices oesophageal	6.7% 21/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.4% 19/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.8% 21/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Flatulence	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.87% 2/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.3% 5/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.8% 12/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Dry mouth	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.1% 9/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.3% 11/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.2% 5/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.2% 7/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.8% 10/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Fatigue	11.2% 35/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.2% 27/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	11.7% 36/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.5% 15/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	12.2% 27/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	13.0% 27/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
General disorders Oedema peripheral	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.6% 6/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.9% 13/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.7% 16/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Urinary tract infection	9.3% 29/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	14.9% 44/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.7% 27/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.6% 13/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	17.2% 38/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	15.0% 31/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Upper respiratory tract infection	7.1% 22/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.4% 19/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.8% 18/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.9% 9/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.4% 23/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	11.1% 23/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Sinusitis	5.8% 18/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.8% 20/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.1% 19/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.0% 7/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.0% 22/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.1% 21/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Nasopharyngitis	6.7% 21/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.4% 13/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.9% 15/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.6% 6/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.0% 20/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.8% 12/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations Bronchitis	7.1% 22/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.7% 14/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.9% 9/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.6% 6/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.9% 13/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.8% 10/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Infections and infestations COVID-19	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.0% 7/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.5% 21/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	15.0% 31/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Investigations Low density lipoprotein increased	1.6% 5/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	11.5% 34/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.7% 33/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.8% 11/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	14.0% 31/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.2% 17/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Investigations Blood bilirubin increased	3.5% 11/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.7% 14/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.5% 17/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.0% 7/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.3% 14/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.8% 12/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Investigations Blood creatinine increased	3.2% 10/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.7% 14/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.2% 13/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.5% 8/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.6% 19/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.7% 16/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Metabolism and nutrition disorders Diabetes mellitus	2.9% 9/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.1% 18/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.8% 21/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.5% 8/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.7% 17/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.1% 21/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Metabolism and nutrition disorders Hyperlipidaemia	1.9% 6/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.8% 17/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.1% 22/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.0% 7/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.8% 15/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.2% 17/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.7% 4/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.7% 6/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.8% 10/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Arthralgia	11.2% 35/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.5% 22/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.1% 28/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.5% 15/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.9% 24/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	14.0% 29/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Back pain	4.8% 15/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.4% 19/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.8% 18/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.6% 6/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.5% 21/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.7% 20/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Muscle spasms	3.5% 11/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.1% 12/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.2% 16/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.1% 18/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.7% 16/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Pain in extremity	3.8% 12/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.8% 17/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.3% 7/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.7% 4/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.7% 17/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.3% 9/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.87% 2/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.7% 6/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.8% 10/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Headache	8.3% 26/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.4% 16/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.5% 20/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.5% 15/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.6% 19/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	10.1% 21/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Nervous system disorders Dizziness	3.2% 10/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.7% 14/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.5% 14/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.6% 6/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.8% 15/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.8% 12/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Psychiatric disorders Insomnia	4.5% 14/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.4% 16/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.2% 10/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.3% 3/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.2% 16/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.3% 11/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Cough	3.5% 11/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	4.7% 14/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.1% 19/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	2.6% 6/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.3% 14/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	8.2% 17/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.2% 7/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	1.7% 5/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.9% 12/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.43% 1/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.6% 8/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.8% 14/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Skin and subcutaneous tissue disorders Pruritus	31.4% 98/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	40.7% 120/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	57.3% 177/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	31.2% 72/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	43.9% 97/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	58.0% 120/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Skin and subcutaneous tissue disorders Rash	4.5% 14/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.4% 10/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	9.4% 29/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.1% 14/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	6.8% 15/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	11.1% 23/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.
Vascular disorders Hypertension	0.00% 0/312 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/295 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	0.00% 0/309 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	3.5% 8/231 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	5.0% 11/221 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.	7.7% 16/207 • Up to 18 months for DB phase and Up to 1 year for OLE phase Safety Population: included all randomized participants who received at least 1 dose of investigational product (OCA or placebo). 3 participants from ITT Population did not receive study treatment, hence were not included in Safety Population.

Additional Information

Medical Information

Intercept Pharmaceuticals, Inc.

Phone: 844-782-4278

Email: medinfo@interceptpharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee Principal Investigators must wait 18 months after the study ends to publish their results and a multi-center publication must come first. The sponsor has a 45-day review period with the option to extend to an additional 90 days.
• Publication restrictions are in place

Restriction type: OTHER